We have characterized the transduction of mouse somatosensory cortical neuron types by recombinant AAV pseudotyped with serotype 1 capsid selleck products (rAAV2/1) and by recombinant lentivirus pseudotyped with the vesicular stomatitis virus (VSV) glycoprotein. Both vectors used human synapsin (hSyn) promoter driving DsRed-Express. We demonstrate that high titer rAAV2/1-hSyn efficiently transduces

both cortical excitatory and inhibitory neuronal populations, but use of lower titers exposes a strong preference for transduction of cortical inhibitory neurons and layer 5 pyramidal neurons. In contrast, we find that VSV-G-LV-hSyn principally labels excitatory cortical neurons at the highest viral titer generated. These findings demonstrate that endogenous tropism of rAAV2/1 and 8-Bromo-cAMP nmr VSV-G-LV can be used to obtain preferential gene expression in mouse somatosensory cortical inhibitory and excitatory neuron populations, respectively. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Trisomy of human chromosome 21 (Hsa 21) causes the pathological characteristics of Down syndrome (DS). Little is known about the mechanisms by which trisomy 21 affects the expression of genes on

other chromosomes. Using a mouse model of DS, the Ts65Dn mouse, we have performed mRNA and protein measurements to identify genes on chromosomes not syntenic with Hsa 21 whose expression

is affected by the presence of three copies of genes between loci MrpI39 and Znf295 on mouse chromosome 16 (Mmu 16). We report the upregulation of beta-catenin, located on mouse chromosome 9 (Mmu 9) in Ts65Dn brain. Using immunocytochemistry on Ts65Dn and control mouse brain tissue, we observed a striking increase in beta-catenin expression selleck specifically in the endothelial cells lining the cerebral blood vessels of the Ts65Dn mice. Since beta-catenin is involved in cell-cell adhesion, upregulation of this protein in DS may alter adherens protein interactions that are involved in the normal functions of endothelial cells. Elevated beta-catenin might be responsible for altered endothelial cell function/s leading to the impairment of brachial flow velocity observed in DS. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“In the hamster brainstem estrogen receptor-alpha-immunoreactive neurons (ER-alpha-IR) are present in the nucleus para-retroambiguus (NPRA), located in the caudal ventrolateral medulla (CVLM) ventrolaterally to the nucleus retroambiguus (NRA). NPRA neurons project mainly to the thoracic and upper lumbar cord and are probably involved in the autonomic adaptations during the estrous cycle. The periaqueductal gray (PAG), projecting to the CVLM, also contains ER-alpha-IR neurons.

A thromboembolectomy was performed and, after treatment of the ischemic complications, the aneurysm was repaired by open surgery. Embolization from aneurysms in the setting of a trauma is a challenge for the vascular surgeon, also because of its rare occurrence. We describe the management and discuss the operative

strategy we opted for in this patient. (J Vasc Surg NU7441 chemical structure 2011;54:840-3.)”
“Dimethylsulfoniopropionate (DMSP) and dimethylsulfide (DMS) are key compounds in the global sulfur cycle. Moreover, DMS is particularly important in climate regulation owing to its role in cloud formation. Reef building corals are major contributors to the production of these two compounds and also form diverse and complex associations with bacteria, which are known to play a crucial role in the degradation of DMSP and DMS. Here, we highlight an extensive overlap between bacterial species implicated in DMSP/DMS degradation and those associated with corals, leading to the hypothesis that these two compounds play a major role in structuring coral-associated bacterial communities, with selleck chemicals important consequences for coral health and the resilience of coral reefs. We also explore the publically available metagenome databases and show that genes implicated in DMSP metabolism are abundant in the viral component of coral-reef-derived metagenomes, indicating that viruses can act as a reservoir for such genes.”
“An

intracellularly expressed defective human immunodeficiency virus type-1 (HIV-1) protease (PR) monomer could function as a dominant-negative inhibitor of the enzyme that requires dimerization for activity. Based on in silico studies, two mutant PRs harboring hydrophilic mutations, capable of forming favorable inter- and intra-subunit interactions, were selected: PR(RE) containing Asp25Arg and Gly49Glu mutations, and PR(RER) containing an additional Ile50Arg mutation. The mutants were expressed VE 822 and tested by PR assays, nuclear magnetic resonance (NMR) and

cell culture experiments. The mutant PRs showed dose-dependent inhibition of the wild-type PR in a fluorescent microtiter plate PR assay. Furthermore, both mutants were retained by hexahistidine-tagged wild-type HIV-1 PR immobilized on nickel-chelate affinity resin. For the first time, heterodimerization between wild-type and dominant-negative mutant PRs were also demonstrated by NMR spectroscopy. (1)H-(15)N Heteronuclear Single Quantum Coherence NMR spectra showed that although PR(RE) has a high tendency to aggregate, PR(RER) exists mainly as a folded monomer at 25-35 mu M concentration, but in the presence of wild-type PR in a ratio of 1:1, heterodimerization occurs with both mutants. While the recombinant virus containing the PR(RE)sequence showed only very low level of expression, expression of the viral proteins of the virus with the PR(RER) sequence was comparable with that of the wild-type.

A large number of software tools have been proposed for the above-mentioned tasks. However, it is not the aim of this review to cover all software tools, but rather discuss common data analysis strategies used by

various algorithms for each of the above-mentioned steps in a non-redundant approach Linsitinib mouse and to argue that there are still some areas which need improvements.”
“An otherwise healthy 45-year-old man presented with a 4-week history of nonpainful discoloration of the maxillary gingiva. He had no history of pigmented skin lesions. An otherwise healthy 45-year-old man presented with a 4-week history of nonpainful discoloration of the maxillary gingiva. He had no history of pigmented skin lesions. Intraoral examination showed areas of the gingiva that were black. The lesion was a pigmented

macule, 1.5 cm by 4 cm in greatest dimension, with asymmetric and irregular borders and colors. Histopathological examination revealed an infiltrating lentiginous melanoma. Oral melanoma is a rare neoplasm. Exposure to the sun is clearly linked to cutaneous melanoma but is not clearly associated with oral melanoma. The patient underwent partial maxillectomy with 2-cm margins, but he declined adjuvant radiotherapy …”
“The ability to sequence DNA rapidly, inexpensively and in a high-throughput fashion provides a unique opportunity to sequence whole genomes of a large number of species. The cataloging Selleck JIB04 of protein-coding genes from these https://www.selleck.cn/products/ITF2357(Givinostat).html species, however, remains a non-trivial task with the majority of initial genome annotation dependent on the use of gene prediction algorithms. Recent advances in mass spectrometry-based proteomics now enable generation of accurate

and comprehensive protein sequence of tissues and organisms. Proteogenomics allows us to harness the wealth of information available at the proteome level and apply it to the available genomic information of organisms. This includes identifying novel genes and splice isoforms, assigning correct start sites and validating predicted exons and genes. It is also possible to use proteogenomics to identify protein variants that could cause diseases, to identify protein biomarkers and to study genome variation. We anticipate proteogenomics to become a powerful approach that will be routinely employed by ‘Genome and Proteome Centers’ of the future.”
“Purpose: Despite its established efficacy in reducing recurrence rates for patients with urothelial carcinoma, immediate intravesical chemotherapy is reportedly used infrequently. Accordingly, the Urological Surgery Quality Collaborative implemented a project aimed at understanding and improving the use of immediate intravesical chemotherapy.

Results are discussed in reference

to task and procedure characteristics that may influence the extent to which item-specific control and/or contingency learning contribute to the ISPC effect. (C) 2013 Elsevier Ltd. All rights reserved.”
“Dense deposit disease and glomerulonephritis with isolated C3 deposits are glomerulopathies characterized by deposits of C3 within or along the glomerular basement membrane. Previous studies found a link between dysregulation of the complement alternative pathway and the pathogenesis of these diseases. We analyzed the role of acquired and genetic complement abnormalities in a cohort of 134 patients, of whom 29 have dense deposit disease, 56 have glomerulonephritis Navitoclax with isolated C3 deposits, and 49 have primary membranoproliferative glomerulonephritis type I, with adult and pediatric onset. A total of 53 patients presented with www.selleckchem.com/products/GDC-0941.html a low C3 level, and 65 were positive for C3 nephritic factor that was significantly more frequently detected in patients with dense deposit disease than in other histological types. Mutations in CFH and CFI genes were identified in 24 patients associated with a C3 nephritic factor in half the cases. We found evidence for complement alternative pathway dysregulation

in 26 patients with membranoproliferative glomerulonephritis type I. The complement factor H Y402H variant was significantly increased in dense deposit disease. We identified

second one at-risk membrane cofactor protein (MCP) haplotype for glomerulonephritis with isolated C3 deposits and membranoproliferative glomerulonephritis type I. Thus, our results suggest a critical role of fluid-phase alternative pathway dysregulation in the pathogenesis of C3 glomerulopathies as well as in immune complex-mediated glomerular diseases. The localization of the C3 deposits may be under the influence of MCP expression.

Kidney International (2012) 82, 454-464; doi:10.1038/ki.2012.63; published online 28 March 2012″
“Objective: To assess whether alleged childhood maltreatment is associated with daily cortisol secretion in women with chronic pain. Method: Women with fibromyalgia (FM group, n = 35) or with osteoarthritis only (OA group, n = 35) completed diaries and collected three saliva samples daily for 30 days, with compliance monitored electronically. Childhood abuse and neglect were assessed by self-report (Childhood Trauma Questionnaire-short form [CTQ-sf]). Multilevel regression analyses estimated associations between maltreatment and diurnal cortisol levels and slopes, controlling for depressive symptoms, posttraumatic stress disorder (PTSD), and daily experience variables. Results: Women reporting more severe childhood maltreatment had higher cortisol throughout the day. The estimated effect of CTQ on log cortisol (beta = 0.007, p = .001) represents a 0.

Concordantly, LTP was enhanced by acutely blocking ErbB4 in wild-type animals, indicating that ErbB4 activity constitutively suppresses LTR Moreover, increasing ErbB4 signaling further suppressed LTP. By contrast, altering ErbB4 activity did not affect basal synaptic transmission or short-term facilitation. Our findings suggest that cognitive deficits in schizophrenia may be a consequence of hyperfunction of ErbB4 signaling leading to suppressed glutamatergic synaptic plasticity, thus opening new approaches for the treatment of this disorder.”
“Surface-treated titanium dioxide (TiO2) particles

coated with vanadium pentoxide (V2O5) are used industrially for selective catalytic reactions such selleck chemicals llc as the removal of nitrous oxide from BMS-777607 exhaust gases of combustion power plants (SCR process) and in biomaterials for increasing the strength of implants. In the present study, untreated ultrafine TiO2 particles ( anatase, diameter: 30-50 nm) and vanadium pentoxide (V2O5)- treated anatase particles were tested for their cyto- and genotoxic effects in V79 cells ( hamster lung fibroblasts). Cytotoxic effects of the particles were assessed by trypan blue exclusion, while genotoxic effects were investigated by micronucleus (MN) assay. In addition,

the generation of reactive oxygen species (ROS) was determined by the acellular method of electron spin resonance technique (ESR) and by the cellular technique of determination of thiobarbituric acid-reactive substances (TBARS). Our results demonstrate that V2O5-treated TiO2 particles induce more potent cyto- and genotoxic effects than untreated particles. Further, acellular and cellular radical formation was more pronounced with V2O5-anatase than untreated MK-4827 purchase anatase. Thus, data indicate that V2O5-treated TiO2 particles were

more reactive than natural anatase and capable of inducing DNA damage in mammalian cells through production of free radicals.”
“A simultaneous evaluation of presynaptic and postsynaptic dopaminergic positron emission tomography markers, the dopamine transporters and the dopamine D-2-like receptors, was performed in eight patients with parkinsonian phenotype of multiple system atrophy. Both presynaptic and postsynaptic markers were revealed to have declined in such a manner that they kept strong positive correlation throughout the striatum of all patients, suggesting that the degeneration process in the striatum may involve the entire structure of the dopaminergic synapse. In two L-3,4,dihydroxyphenyl-alanine-responsive cases, the balance of decline in two markers was relatively shifted to presynaptic dominant side.

Our aim was to analyze the results of laryngotracheal reconstruction as a treatment for complex laryngotracheal stenosis in adults, considering postoperative and long-term outcome.

Methods: Laryngotracheal reconstruction (laryngeal split with anterior and posterior interposition of a rib cartilage graft) has been used in our institution to manage glottic/subglottic stenosis restricted to the larynx; laryngotracheal reconstruction associated with cricotracheal resection has been used to treat glottic/subglottic/upper tracheal stenosis (extending beyond the second tracheal

ring). A retrospective study was conducted, including all patients with complex laryngotracheal stenosis treated surgically in our institution from January of 2002 until December of 2005.

Results: Twenty

patients (10 male Selleckchem OSI-027 and 10 female patients; average age, 36.13 years; age range, 18-54 years) were included. There were no deaths, and the postoperative complications were as follows: dysphonia, 25%; subcutaneous emphysema, 10%; tracheocutaneous fistula, 20%; wound infection, 15%; and bleeding, 5.0%. Eighty percent of the patients were completely decannulated after a mean of 23.4 months of follow-up (range, 4 -55 months).

Conclusions: Laryngeal split with anterior and posterior cartilage graft interposition as an isolated procedure or associated with a cricotracheal resection is a feasible and low-morbidity alternative for complex laryngotracheal stenosis treatment.”
“Objective: Lung ischemia-reperfusion injury selleck chemical is associated with impaired gas exchange DNA-PK inhibitor from increased edema formation and surfactant inactivation. Surfactant replacement therapy is believed to improve gas exchange and lung function, but its effect on inflammation is less well understood. We therefore examined the effects

of exogenous surfactant on inflammatory and apoptotic factors in the lung in a rat model of lung ischemia-reperfusion injury.

Methods: The left lung in rats was subjected to ischemia for 120 minutes and reperfusion for as long as 240 minutes. Sham-treated animals underwent sham surgery and mechanical ventilation for equivalent times. Rats received porcine surfactant or saline solution intratracheally either before or just after ischemia. Lungs were analyzed histopathologically and for expressions of inducible nitric oxide, cytokines, and caspase-3.

Results: Lung ischemia-reperfusion injury resulted in worse lung histopathologic characteristics than in sham-operation animals. At 2 hours of reperfusion, lung ischemia-reperfusion injury animals showed increased pulmonary caspase-3 expression. Moreover, lung ischemia-reperfusion injury resulted in inducible nitric oxide expression at all time points. Exogenous surfactant resulted in less inflammatory cell infiltration and edema in the lungs relative to saline-treated animals.

The presence of multiple chemosensory pathways might enable bacteria to tune their tactic responses to different environmental conditions.”
“Background and Aims: Time of onset of antipsychotic action is still a debated matter.

We aimed to replicate and extend previous findings that early response can predict subsequent non-response. Methods: Bcl-2 inhibitor 86 acutely psychotic patients treated with haloperidol were studied. Results: A PANSS reduction <= 16% at 1 week predicts non-response at 3 weeks of treatment (specificity 92%, sensitivity 82%). Conversely, a PANSS reduction >= 23% at 1 week of treatment predicts response at 3 weeks, with a specificity of 84% and a sensitivity of 86%. Conclusion: Our results confirm that an early response to antipsychotic treatment accurately predicts the treatment effectiveness and extends it to a prediction performed as early as 1 week. Copyright (c) 2012 S. Karger AG, Basel”
“Objective: Mounting evidence indicates that low levels of n-3 polyunsaturated fatty acids (PUFAs) play a role in the pathophysiology

of a large number of psychiatric disorders. In light of the suboptimal n-3 PUFAs intake due to poor dietary habits among substance abusers and the strong associations between aggression, anxiety and substance use disorders we examined if insurance of adequate intakes of n-3 PUFAs with supplementation would decrease their anger and anxiety scores.

Method: Substance abusers (n=22) were assigned to either 3 g of n-3

PUFAs, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or soybean oil in identically looking capsules. The Selleckchem VX-661 trial was double-blind, Navitoclax clinical trial randomized and lasted 3 months. Anger and anxiety scales were administered at baseline and once a month thereafter. Blood samples were collected at baseline and at the end of the trial.

Results: Patients’ dietary intakes of n-3 PUFAs fell below recommended levels. Assignment to n-3 PUFA treatment was accompanied by significant decreases in anger and anxiety scores compared to placebo assignment. These changes were associated with increases in plasma levels of both EPA and DHA but an increase in EPA was more robustly correlated with low end-of-trial anxiety scores and an increase in DHA was more robustly correlated with low end-of-trial anger scores.

Conclusion: These pilot data indicate that ensuring adequate n-3 PUFA intake via supplementation benefits substance abusers by reducing their anger and anxiety levels. The strong correlations between an increase in plasma EPA and lower anxiety scores and between an increase in plasma DHA and lower anger scores suggests a need for the further exploration of the differential responses to these two n-3 PUFAs in different psychiatric conditions. Published by Elsevier Inc.”
“Primary varicella-zoster virus (VZV) infection in humans produces varicella (chickenpox), after which the virus becomes latent in ganglionic neurons.

This case raises an important ethical issue of human life expectancy and the appropriateness of high-risk surgery on a centenarian.(J Vase Surg 2011;53:216-8.)”
“Lindane

(gamma-hexachlorocyclohexane), a persistent organo-chlorine insecticide widely used in developing countries, has a negative effect as a polluting agent of soil and surface waters. Plants can be used for remediation of organic pollutants and their efficiency can be enhanced by introduction of heterologous genes. Mammalian cytochrome P4502E1 (CYP2E1), an important monooxygenase is involved in the degradation of a wide selleck chemical range of xenobiotics including environmental pollutants/herbicides and pesticides. Here, we report the development of transgenic tobacco plants expressing human CYP2E1 and the

efficacy of plants for remediation of lindane. Transgenic tobacco plants with CYP2E1 showed enhanced tolerance to lindane when grown in hydroponic medium and soil compared to control plants. Remediation of (14)C-labeled lindane from hydroponic medium was higher in transgenic plants compared to that of control plants, with the best performing line showing 25% BIBW2992 chemical structure higher removal of lindane from solution than control plants. Similar results were seen in plants grown in soil spiked with lindane. The present study has shown that transgenic plants expressing CYP2E1 gene have potential use for remediation of lindane from contaminated solutions and soil.”
“Objective: Diabetic peripheral neuropathy is a major complication of diabetes mellitus (DM) and is the leading cause of foot ulceration and lower extremity amputations (LEAs). The

purpose of this systematic review is to evaluate current evidence regarding the prognostic value of the Semmes Weinstein monofilament examination (SWME) in predicting foot ulceration and LEA in Bcl-w patients with DM.

Methods: The MEDLINE/PubMed database was searched through November 2009 for articles pertaining to diabetic foot and SWME with no language or publication date restrictions. Prognostic studies with original data assessing the predictive value of SWME for foot ulceration or LEA in patients with DM were included in the selection. Data were systematically extracted and analyzed by two independent investigators. Absolute risks and relative risks were determined for each study.

Results: Of the 863 studies identified, nine articles were relevant, involving 11,007 patients with DM. Six studies were identified that assessed the prognostic value of SWME regarding diabetic foot ulceration. The relative risk for patients with a positive SWME result versus those with a negative result ranged from 2.5 (95% confidence interval [CI], 2.0 to 3.2) to 7.9 (95% CI, 4.4 to 14.3) in the identified studies with follow up between 1 and 4 years. Three of the studies assessed the risk of LEA with a positive SWME result. The relative risk for LEA ranged from 1.7 (95% CI, 1.1 to 2.6) to 15.1 (95% CI, 4.3 to 52.

Methods and Results: The antagonistic activity of JA was tested in vitro; it exhibited strong inhibition against

some important phytopathogens and postharvest pathogens. Crude antibiotic production was extracted with methanol from the precipitate by adding 6 mol l(-1) HCl to the bacillus-free culture broth. The crude extract was run on Diamonsil C-18 column (5 mu m, 250 x 4.6 mm) in HPLC system to separate the antibiotics. Major antibiotics were classified into three lipopeptide families according to electrospray ionization-mass spectrometry analysis. Subsequently, the classification of antibiotics was confirmed with typical collision-induced dissociation Torin 2 fragments.

Conclusions: Three Flavopiridol kinds of antibiotics were isolated from B. subtilis JA and were identified to the lipopeptide families, surfactin,

iturin and fengycin. These compounds could function as biocontrol agents against a large spectrum of pathogens.

Significance and Impact of the Study: This study provided a reliable and rapid method for isolation and structural characterization of lipopeptide antibiotics from B. subtilis.”
“OBJECTIVE: In this case report, we present a patient with normal pressure hydrocephalus in whom a lumbar drainage trial yielded a false-negative result secondary to cervical spondylosis.

CLINICAL PRESENTATION: An 80-year-old woman presented with classic symptoms of normal pressure hydrocephalus as well as evidence of cervical myelopathy. Magnetic resonance imaging of the brain and spine showed enlarged ventricles and single-level cervical canal narrowing.

INTERVENTION: An initial lumbar drainage trial was performed, which revealed negative results. The patient then underwent cervical decompression and fusion. Despite this procedure, the patient’s symptoms continued to worsen. A repeat lumbar drainage trial was performed with positive results. Subsequently, a ventriculoperitoneal shunt was placed, resulting in significant improvement of her symptoms.

CONCLUSION: This case report illustrates how altered cerebrospinal

fluid flow dynamics may impact the accuracy of the lumbar spinal drainage trial in patients with normal pressure hydrocephalus.”
“Aims: To investigate the suitability of Hugh and Leifson’s medium (HLM) as the basis of a simple screening test to differentiate between Immunology & Inflammation inhibitor contaminants and Arcobacter spp. during their isolation from foodstuffs.

Methods and Results: Characterized Arcobacter spp. were obtained from recognized culture collections. Wild-type isolates of Arcobacter spp. and contaminants were obtained using published isolation protocols. Retail packs of red meats were used as the source of the isolates. Eighteen defined Arcobacter spp. gave no reaction on HLM, as did 10 local wild-type isolates. Overall 163 contaminants were studied for oxidative reactions on HLM and 86% of isolates demonstrated this property.

We report here an improved radiosynthesis and purification of [F-18]EF5 by utilizing an electroformed nickel (Ni) target for [F-18]F-2 production, and Oasis (R) HLB cartridges for on-line solid phase extraction of [F-18]EF5

prior to HPLC purification.

Methods: [F-18]F-2 was produced by deuteron bombardment of neon plus F-2 in an Ni target, and bubbled through the radiolabelling precursor solution. Purification was achieved by extracting the contents of the crude reaction mixture onto Oasis HLB cartridges, and subsequently eluted onto a semi-preparative HPLC column for further separation. Purified [F-18]EF5 was evaluated in small animal PET studies using HCT116 tumor xenografts in nude mice.

Results: The electroformed Ni target enabled recovery of >75% of the radioactivity from the cyclotron https://www.selleckchem.com/products/brigatinib-ap26113.html target, resulting in 16.2 +/- 2.2 GBq (438 +/- 58 mCi) of [F-18]F-2 available for the synthesis. Use of Oasis cartridges yielded a less complex mixture for purification. On average, 1140 +/- 200 MBq (30.8 +/- 5.4 mCi) of [F-18]EF5 were find more collected at EOS. Small animal PET imaging studies showed specific retention of [F-18]EF5 in tumors, with tumor-to-muscle ratios of 2.7 +/- 0.3 at aboutl 60 min after

injection.

Conclusion: A simple procedure has been developed for the routine synthesis of [F-18]EF5 in amounts and purity required for clinical studies. This new method avoids the need for TFA evaporation and also enables facile automation of the synthesis using commercially available radiosynthesis modules. (c). 2012 Elsevier Inc. All rights reserved.”
“Objectives: We reviewed the use of pediatric mechanical circulatory support before and after transplantation to examinine current results and future strategies.

Methods: All patients listed for transplantation from January 2000 to December 2010 who required either extracorporeal membrane oxygenation (ECMO) or ventricular assist device (VAD) support before (“”intention to transplant”) or

after transplantation were included. Indications for mechanical assistance, age, weight, duration of support, complications while on support, causes of death, learn more and overall actuarial survival were recorded.

Results: Thirty-seven patients were received VADs; 32 (86.5%) survived to transplantation. Postoperative hemorrhagic or thrombotic complications affected all of those under 15 kg. One patient in the survivor cohort demonstrated focal neurologic findings. Three (8.1%) had panel reactive antibody levels of 10% or more while on device support; all received transplants. ECMO as an intention to bridge to transplantation was used in 28 patients; 7 died, 7 were weaned, and 14 were bridged to transplantation. Nineteen patients required ECMO after transplantation; 3 additional patients had percutaneous VAD support for late rejection. There was a significant (P = .