e., clinician-led. Well-matched healthy individuals were also scanned to control for non-specific changes over a 3-week period.

After 3 weeks of anti-psychotic treatment, significant grey matter volume increase in the right caudate, superior and inferior frontal gyrus, precentral gyrus, and left inferior parietal lobule was noted. However, after 8 weeks of anti-psychotic treatment, volume increase in the right thalamus and bilateral cerebellum was observed. Significant grey matter reduction was detected in the left medial frontal gyrus at both 3- and 8-week intervals.

Early increase in striatal volume change occurs as early as 3 weeks after anti-psychotic treatment, whilst thalamic volume increase

is apparent later, MK-2206 solubility dmso by

8 weeks of treatment. We speculate that drug-mediated neuroplasticity may provide a biomarker for clinical LY3009104 clinical trial recovery.”
“Objective: The goal of this study was to quantify the net increase in resource use associated with complications after isolated mitral valve surgery.

Methods: Deidentified patient-level claims data on a random sample of mitral valve operations performed in the United States from January 1, 2006, to December 31, 2007, were obtained from the National Inpatient Sample (n = 16,788). Patients with major concomitant cardiac procedures were excluded from the analysis for a net sample size of 6297 patients. Risk-adjusted median total hospital costs and length of stay were analyzed by major complications, including pneumonia, sepsis, stroke, renal failure requiring hemodialysis, cardiac tamponade, myocardial infarction, gastrointestinal bleed, and venous thromboembolism.

Results: There were a total of 1323 complication events that occurred in 1089 patients. The most common complication was pneumonia (n = 346, 5.5%), which was associated with a $29,692 increase

in hospital costs and a 10.2-day increase in median length of stay (P < .001). The most costly complication was cardiac tamponade, which resulted in an increase in hospital cost of $56,547 and an increase in length of stay of 19.3 days (P < .001). There was a stepwise association between the hospital costs and length of stay and the number of complications per Lapatinib purchase patient (P < .001). There was also a significant association between the discharge location and the occurrence of a complication, with 25% more patients who underwent routine home discharge when there were no complications (P < .001).

Conclusions: In patients undergoing isolated mitral valve surgery, postoperative complications were associated with significant increases in mortality, hospital costs, and length of stay, as well as with discharge location. With growing national attention to improving quality and containing costs, it is important to understand the nature and impact of complications on outcomes and costs.

Optimizing the texture of the implant and its position in the scrotum may improve outcome. However, patients should be counseled about possible adverse implications in terms of physical exercise or sexual activity.”
“We Selleck ARS-1620 examined event-related brain potential (ERP) modulations during the anticipation and processing of unpleasant pictures under instructions to cognitively decrease and increase negative emotion. Instructions to decrease and increase negative emotion modulated the ERP response to unpleasant pictures in the direction of emotional intensity beginning around 400 ms and lasting several seconds. Decrease, but not increase, instructions also elicited enhanced

frontal negativity associated with orienting and preparation prior to unpleasant picture CB-839 onset. Last, ERP modulation by unpleasant pictures began around 300 ms, just

prior to regulation effects, suggesting that appraisal of emotion occurs before emotion regulation. Together, the current findings underscore the utility of ERPs in illuminating the time course of emotion modulation and regulation that may help to refine extant theoretical models.”
“Human brain imaging has provided much information about pain processing and pain modulation, but brain imaging in rodents can provide information not attainable in human studies. First, the short lifespan of rats and mice, as well as the ability to have homogenous MTMR9 genetics and environments, allows for longitudinal studies of the effects of chronic pain

on the brain. Second, brain imaging in animals allows for the testing of central actions of novel pharmacological and nonpharmacological analgesics before they can be tested in humans. The two most commonly used brain imaging methods in rodents are magnetic resonance imaging (MRI) and positron emission tomography (PET). MRI provides better spatial and temporal resolution than PET, but PET allows for the imaging of neurotransmitters and non-neuronal cells, such as astrocytes, in addition to functional imaging. One problem with rodent brain imaging involves methods for keeping the subject still in the scanner. Both anesthetic agents and restraint techniques have potential confounds. Some PET methods allow for tracer uptake before the animal is anesthetized, but imaging a moving animal also has potential confounds. Despite the challenges associated with the various techniques, the 31 studies using either functional MRI or PET to image pain processing in rodents have yielded surprisingly consistent results, with brain regions commonly activated in human pain imaging studies (somatosensory cortex, cingulate cortex, thalamus) also being activated in the majority of these studies. Pharmacological imaging in rodents shows overlapping activation patterns with pain and opiate analgesics, similar to what is found in humans.

This study assessed whether the intramuscular infusion of a combination cell product represents a viable, effective, and lasting therapeutic modality to improve perfusion in severely ischemic limbs.

Methods: Patients with limb ischemia (n = 26) received an intramuscular (gastrocnemius) infusion of the combination cell product in the most ischemic leg and a placebo product in the (less ischemic) JQ1 cost contralateral leg. Clinical follow-up (months 0.5, 1, 2, and 4 postinfusion) included evaluation of pain-free walking time, ankle-brachial index, perfusion scintigraphy, and quality of life survey.

Results: No adverse events occurred after infusion. Efficacy assessment indicated that after cell infusion there was a

significant improvement in walking time and ankle-brachial index. In addition, technetium-99m-tetrofosmin scintigraphy demonstrated a significant increase of perfusion in the treated limbs compared with the respective control legs.

Conclusions: This phase II clinical trial shows that the use of a combination cell therapy is safe and effective in increasing blood flow in the ischemic legs of patients with limb ischemia.

(J Thorac Cardiovasc Surg 2012;144:377-82)”
“alpha(2)-Adrenergic see more agonists simulate norepinephrine (NE) action on alpha(2) receptors of sympathetic neurons to mediate feedback inhibition of NE release. These agents are used as valuable adjuncts for management of hypertension and for anesthesia. Their action, equivalent to NE on alpha 2 adrenergic receptors, raises the question whether alpha 2 agonists may also target NE transporters (NETs),

another major control mechanism for noradrenergic neurotransmission. We thus investigated the effect of alpha(2) agonists on transport of the NE analog, I-131-metaiodobenzylguanidine (MIBG). Results from this investigation showed that xylazine and dexmedetomidine dose-dependently blocked [H-3]nisoxetine binding in neuron-like SK-N-SH cells. Furthermore, the agents acutely suppressed cellular MIBG uptake in a dose-dependent manner. This effect was uninfluenced by the alpha 2 antagonist yohimbine, but was completely reversed by drug removal. There was no change in membrane NET density by the agents. Moreover, saturation analysis showed that xylazine and dexmedetomidine significantly increased Km without affecting V-max, indicating competitive learn more inhibition of MIBG transport. Thus, the alpha(2) adrenergic agonists xylazine and dexmedetomidine, acutely suppress NET function through competitive inhibition of substrate transport, likely by direct interaction on a region that over-laps with the nisoxetine binding site. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“We developed streamlined, automated purification protocols for the production of milligram quantities of untagged recombinant human cyclophilin-A (hCypA) and untagged human proliferating cell nuclear antigen (hPCNA) from Escherichia coli, using the AKTAxpress(TM) chromatography system.

Here, we investigated whether such an increase also occurs in other brainstem nuclei. six pairs of male Sprague-Dawley rats were exposed to CIH or sham treatment for 10 h/day for 35 days, with 02 level oscillating between 24% and 7% every 3 min. Brainstem sections were immunohistochemically processed for dopamine-beta-hydroxylase, a marker for norepinephrine. Noradrenergic terminal varicosities were counted MEK162 in the center of the trigeminal motor nucleus (Mo5) and the interpolar part of the spinal trigeminal sensory nucleus

(Sp5). In the Mo5, noradrenergic varicosities tended to be 9% more numerous in CIH- than sham-treated rats, and in the Sp5 they were 18% more numerous in CIH rats (184 +/- 9 vs. 156 +/- 8 per 100 x 100 mu m counting box; p = 0.03, n = 18 section pairs).These data suggest that CIH elicits sprouting of noradrenergic terminals in multiple motor and sensory regions of the lower brainstem. This may alter motor and cardiorespiratory outputs

and the transmission of cardiorespiratory and motor reflexes in CIH rats and, by implication, in OSA patients. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Transporters, such as multidrug resistance P-glycoproteins (MDR), multidrug resistance-related proteins (MRP) and organic anion transporters (OATs), are involved in xenobiotic metabolism, particularly the cellular uptake or efflux of xenobiotics (and endobiotics) or their metabolites. The olfactory epithelium is exposed to both inhaled xenobiotics and those coming from systemic circulation. click here This tissue has been described as a pathway for xenobiotics to the brain via olfactory perineural

space. Thereby, olfactory transporters and xenobiotic metabolizing enzymes, dedicated to the inactivation and the elimination of xenobiotics, have been involved in the toxicological protection of the brain, the olfactory epithelium itself and the whole body. These proteins could selleck screening library also have a role in the preservation of the olfactory sensitivity by inactivation and clearance of the excess of odorant molecules from the perireceptor space. The goal of the present study was to increase our understanding of the expression and the localization of transporters in this tissue. For most of the studied transporters, we observed an opposite mRNA expression pattern (RT-PCR) in the olfactory epithelium compared to the liver, which is considered to be the main metabolic organ. Olfactory epithelium mainly expressed efflux transporters (MRP, MDR). However, a similar pattern was observed between the olfactory epithelium and the olfactory bulb. We also demonstrate distinct cellular immunolocalization of the transporters in the olfactory epithelium. As previously reported, Mrp1 was mainly found in the supranuclear portions of supporting cells.

In all, future studies are needed to better understand the health and functional consequences of body composition among the oldest old.”
“Heterochromatin at pericentric satellites, characterized by a specific chromatin signature and chromocenter organization, is of paramount importance for genome function. Re-establishment of this organization after fertilization takes place in the context of genome-wide epigenetic reprogramming. We review how the asymmetry

in histone variants and post-translational modifications between paternal and maternal genomes and their respective pericentric heterochromatin domains evolve during early cleavage stages in mouse. We draw a parallel between these data and the burst of pericentric ML323 solubility dmso satellite transcription that occurs concomitantly with the dynamic reorganization of the pericentric domains into

chromocenters in two-cell stage embryos. Based on this new angle, we propose that a crucial developmental transition at the two-cell stage allows chromocenter formation by involving non-coding selleck inhibitor satellite transcripts to trigger specific chromatin changes.”
“Mice deficient in the recognition molecules, close homolog of L1 (CHL1) and tenascin-C, show improved and reduced functional recovery, respectively, after spinal cord injury compared with wild-type littermates. In this study, we addressed the question whether the differential functional outcome was paralleled by differences in blood-spinal cord barrier (BSCB) repair in the two mouse strains. We conducted spinal cord compression injuries in knock-out and wild-type mice. BSCB permeability was assessed by measuring the Evans blue spread within the spinal cord tissue at 14-21 days after injury. Results show that CHL1 reduces and tenascin-C enhances BSCB permeability, suggesting a correlation between functional outcome and BSCB repair. NeuroReport 23:479-482 (C) 2012 Wolters Kluwer Health

vertical bar Lippincott Williams & Wilkins.”
“In a functional magnetic resonance imaging experiment, expectancy Cues signaling emotional stimuli were used to study the personality trait of novelty seeking. BOLD responses to emotional expectancy were positively correlated with novelty-seeking scores in the medial prefrontal cortex. This correlation was strongest for the sub-dimension Wortmannin research buy of exploratory excitability. (C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Background. Resistance training programs have been found to improve muscle strength, physical function, and depressive symptoms in middle-aged and older adults. These programs have typically been provided in clinical facilities, health clubs, and senior centers, which may be inconvenient and/or cost prohibitive for some older adults. The purpose of this study was to investigate the effectiveness of an automated telemedicine intervention that provides real-time guidance and monitoring of resistance training in the home.

Methods.

05) with a z-average molecular weight (M(z)) of 433 kDa (stoichiometry 5 7). There was no evidence of reversible self-association for an IgG1-Fc molecule in A5N by itself or in a mixture

containing fluorescently labeled IgG1-Fc and PbA, indicative of PbA self-assembly being mediated through its peptide arms. Self-association increased with pH, NaCl concentration, and anion size (I(-) > Br(-) > Cl(-) > F(-)) but could be inhibited using soluble Trp-, Phe-, and Leu-amide salts (Trp > Phe > Leu). We propose that in the presence of salt (i) anion binding renders PbA self-association competent by neutralizing the peptidyl arginyl and lysyl amines, (ii) self-association occurs via aromatic and hydrophobic interactions between the ..xxCTRWPWMC..xxx..CTRWPWMCxx.. motifs, and (iii) at >10 mg/mL, PbA predominantly exists as heptameric clusters.”
“Inflammasomes MK-4827 nmr are cytosolic protein complexes that stimulate the activation of caspase-1, which

in turn induces the secretion of the inflammatory cytokines Interleukin-1 beta (IL-1 beta) and IL-18. Recent studies have indicated that the inflammasome known as the NOD-like-receptor-family, pyrin domain-containing 3 (NLRP3) inflammasome recognizes several RNA viruses, including the influenza and encephalomyocarditis viruses, whereas the retinoic acid-inducible gene I (RIG-I) inflammasome may detect https://www.selleckchem.com/products/anlotinib-al3818.html vesicular stomatitis virus. We demonstrate that measles virus (MV) infection induces caspase-1-dependent IL-1 beta secretion in the

human macrophage-like cell line THP-1. Gene knockdown experiments indicated that IL-1 beta secretion in MV-infected THP-1 cells was mediated by the NLRP3 inflammasome but not the RIG-I Cell press inflammasome. MV produces the nonstructural V protein, which has been shown to antagonize host innate immune responses. The recombinant MV lacking the V protein induced more IL-1 beta than the parental virus. THP-1 cells stably expressing the V protein suppressed NLRP3 inflammasome-mediated IL-1 beta secretion. Furthermore, coimmunoprecipitation assays revealed that the V protein interacts with NLRP3 through its carboxyl-terminal domain. NLRP3 was located in cytoplasmic granular structures in THP-1 cells stably expressing the V protein, but upon inflammasome activation, NLRP3 was redistributed to the perinuclear region, where it colocalized with the V protein. These results indicate that the V protein of MV suppresses NLRP3 inflammasome-mediated IL-1 beta secretion by directly or indirectly interacting with NLRP3.”
“More than 5 million deaths a year are attributable to tobacco smoking, making it the largest single cause of preventable death worldwide. The primary addictive component in tobacco is nicotine. Its addictive power is exemplified by the fact that by far most attempts to quit smoking fail.

Complete gradual cessation of smoking and solid-fuel use by 2033 could avoid 26 selleck kinase inhibitor million deaths from COPD and 6.3 million deaths from lung cancer; interventions of intermediate magnitude would reduce deaths by 6-31% (COPD) and 8-26% (lung cancer). Complete cessation of smoking and solid-fuel use by 2033 would reduce the projected annual tuberculosis incidence

in 2033 by 1.4-52% if 80% DOTS coverage is sustained, 27-62% if 50% coverage is sustained, or 33-71% if 20% coverage is sustained.

Interpretation Reducing smoking and solid-fuel use can substantially lower predictions of COPD and lung cancer burden and would contribute to effective tuberculosis control in China.

Funding International Union Against Tuberculosis and Lung Disease.”
“There is increasing evidence that impairment of mitochondrial function and oxidative damage are contributing factors to the pathophysiology EPZ-6438 of Parkinson’s disease (PD). Studies have reported decreased levels of the mitochondrial electron transport chain carrier, coenzyme Q(10) (CoQ(10)) in plasma and platelets from PD patients. Although a deficit in peripheral CoQ10 has been reported no studies have assessed the CoQ(10) status of the PD brain. In this study we investigated the CoQ(10) status of the substantia nigra, cerebellum, cortex and striatum brain regions of both PD patients and age-matched controls. The results of this study indicate a significant reduction (p = 0.007) in CoQ(10) concentration

in the cortex region of the brain. In conclusion, the results of this study indicate evidence of a deficit in brain CoQ(10) status may be involved in the pathophysiology of PD. (c) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Background Children with Down’s syndrome have a greatly increased risk of acute megakaryoblastic and acute lymphoblastic leukaemias. Acute megakaryoblastic leukaemia in Down’s syndrome is characterised by a somatic mutation in GATA1. Constitutive activation of the JAK/STAT (Janus kinase and signal transducer and activator of transcription) pathway

occurs in several haematopoietic malignant diseases. We tested the hypothesis that mutations in JAK2 might be a common molecular event in acute lymphoblastic leukaemia associated with Down’s syndrome.

Methods this website JAK2 DNA mutational analysis was done on diagnostic bone marrow samples obtained from 88 patients with Down’s syndrome-associated acute lymphoblastic: leukaemia; and 216 patients with sporadic acute lymphoblastic: leukaemia, Down’s syndrome-associated acute megakaryoblastic leukaemia, and essential thrombocythaemia. Functional consequences of identified mutations were studied in mouse haematopoietic progenitor cells.

Findings Somatically acquired JAK2 mutations were identified in 16 (18%) patients with Down’s syndrome-associated acute lymphoblastic leukaemia. The only patient with non-Down’s syndrome-associated leukaemia but with a JAK2 mutation had an isochromosome 21q.

125 or 0.25 mg/kg, i.p.). Mice injected with SB 222200 had significantly enhanced hyperactivity when challenged with cocaine or a low dose of SKF 82958 (0.125 mg/kg, i.p.) compared to control mice. Brains of mice administered vehicle or SB 222200 for 5 days were harvested after a 7-day drug-free period for dopamine D1 receptor quantification by radioligand binding. [(3)H] SCH 23390 homogenate binding studies showed a 19.7% increase in dopamine D1 receptor density in the striatum of SB 222200 treated mice. These data suggest that repeated blockade of NK-3 receptors enhances subsequent dopamine-mediated behaviors

possibly resulting from dopamine D1 receptor up-regulation in the striatum. (C) 2009 Elsevier Ltd. All rights reserved.”
“Geminiviruses selleck replicate single-stranded DNA genomes through double-stranded intermediates that associate with cellular histone proteins. Unlike RNA viruses, they are subject to RNA-directed methylation pathways that target viral chromatin and likely lead to transcriptional

gene silencing (TGS). Here we present evidence that the related geminivirus proteins AL2 and L2 are able to suppress this aspect of host defense. AL2 and L2 interact with and inactivate adenosine AZD1080 molecular weight kinase (ADK), which is required for efficient production of S-adenosyl methionine, an essential methyltransferase cofactor. We demonstrate that the viral proteins can reverse TGS of a green fluorescent protein (GFP) transgene in Nicotiana

benthamiana when overexpressed from a Potato virus X vector and that reversal of TGS by geminiviruses check details requires L2 function. We also show that AL2 and L2 cause ectopic expression of endogenous Arabidopsis thaliana loci silenced by methylation in a manner that correlates with ADK inhibition. However, at one exceptional locus, ADK inhibition was insufficient and TGS reversal required the transcriptional activation domain of AL2. Using restriction-sensitive PCR and bisulfite sequencing, we showed that AL2-mediated TGS suppression is accompanied by reduced cytosine methylation. Finally, using a methylation-sensitive single-nucleotide extension assay, we showed that transgenic expression of AL2 or L2 causes global reduction in cytosine methylation. Our results provide further evidence that viral chromatin methylation is an important host defense and allow us to propose that as a countermeasure, geminivirus proteins reverse TGS by nonspecifically inhibiting cellular transmethylation reactions. To our knowledge, this is the first report that viral proteins can inhibit TGS.”
“Introduction: Alcohol and nicotine both alter learning, locomotion, and anxiety, yet no study has directly examined the interactive effects of these drugs across these behaviors within subjects. Such a comparison would determine if the drugs produce independent effects on each behavior.

However, on incubation of recombinant H2A with chemically synthesized bio-50-AMP, H2A was observed to be rapidly labeled with biotin in the absence of enzyme. Nonenzymatic biotinylation of a truncated apocarboxylase (BCCP87) has been previously reported (Streaker and Beckett, Protein Sci 2006; 15: 1928-1935), though at a much slower rate than we observe for H2A. The specific attachment sites of nonenzymatically biotinylated recombinant H2A at different time points were identified using mass spectrometry, and were found to consist of a similar pattern of biotin attachment as seen buy Bromosporine in the presence of HCS, with preference for lysines in the highly basic N-terminal region of the histone. None of the lysine sites

within H2A resembles the biotin attachment consensus sequence seen in carboxylases, suggesting a novel mechanism for histone biotinylation.”
“The inbred Roman low- (RLA-I) and high-avoidance (RHA-I) rats used in this study were initially selected and bred for extremely poor vs. rapid acquisition of active two-way avoidance behavior in the shuttle. box. As a result of the selection for divergent avoidance acquisition, clear behavioral differences have been found between RHA and RLA rats in a variety

of tasks related to anxiety and conflict. In rats of these two strains/lines previous brain studies RepSox concentration have been performed, specifically in the striatum, the mesencephalic dopaminergic areas and the prefrontal cortex, as these brain areas are the classical ones for their critical role in sensitization and may play a role in the well-characterized anxiety response. In this study we analyzed, in RHA and RLA groups (N = 5 each), the density of NeuN neurons counterstained with toluidine blue in the cingulate cortex (subdivision 1) and the hippocampus (CA1, CA2 and CA3). A statistical difference

was found in the density of neurons of CA1 and CA2 (p = 0.047 in both) and in the total density of the hippocampus PF477736 (p = 0.009). Contrary to our expectations, significant strain differences for the density of neurons in the cingulate cortex were not found. The relationship between those differences in the hippocampus and the between-strain differences in anxiety and in learning processes depending on anxiety are discussed. (C) 2012 Elsevier Ireland Ltd. All rights reserved.”
“In addition to muscle disease, defects in processing and assembly of the dystrophin-glycoprotein complex (DGC) are associated with a spectrum of brain abnormalities ranging from mild cognitive impairment (MCI) to neuronal migration disorders. In brain, the DGC is involved in the organisation of GABA(A) receptors (GABA(A)Rs) and aquaporin-4 (AQP4)-containing protein complexes in neurons and glia, respectively. During development, defects in the glycosylation of alpha-dystroglycan that impair its ability to interact with the extracellular matrix (ECM) are frequently associated with cobblestone lissencephaly and mental retardation.

This strategy helps avoid complicated open arterial surgery in high-risk patients with associated multiple medical risk factors or hostile scarred groins. (J Vasc Surg 2013; 57: 421-6.)”
“The goal of this study was to identify promising new biomarkers of cadmium by identifying differentially expressed proteins in Paronychiurus kimi after exposure to cadmium. Through proteomic analysis of P. kimi using 1-D PAGE and nano-LC-MS/MS,

36 downregulated proteins and 40 upregulated proteins were found. Some of the downregulated and upregulated proteins were verified by LC-MS/MS analysis after 2-D PAGE. Downregulated proteins in response to cadmium exposure were involved in glycolysis and energy metabolism, chaperones, transcription, reproduction, and neuron growth. In contrast, proteins involved in glycolysis and energy production, neurogenesis, defense systems response find more to bacteria, and protein biosynthesis were upregulated in cadmium-treated collembolans. Cubulin may be a potential biomarker for

the detection of cadmium in P. kimi since this biomarker was able to low levels (3.5 mg/kg) of cadmium. The 14-3-3 zeta was also found to be a potential biomarker for the detection of medium levels (14 mg/kg) of cadmium. Collembolans may be an alternative tool to humans because many collembolans proteins show a high homology to human proteins.”
“Objective: Because PAK inhibitor of the prolonged healing time of diabetic foot ulcers, methods for identifying ways to expedite the ulcer healing process are needed. The angiosome concept delineates the body into three-dimensional blocks of tissue fed by specific source arteries. The aim of this study was to evaluate the benefit of infrapopliteal endovascular revascularization guided by an angiosome model of perfusion in the healing process of diabetic foot ulcers.

Methods: A total of 250 consecutive legs with

diabetic foot ulcers in 226 patients who had undergone infrapopliteal endovascular revascularization in a single center were evaluated. Patient records and periprocedural leg angiograms were reviewed. The legs were divided into two groups depending on whether direct arterial flow to the site of the foot ulcer based on the angiosome concept was ZD1839 supplier achieved (direct group) or not achieved (indirect group). Ulcer healing time was compared between the two groups. A propensity score was used for adjustment of differences in pretreatment covariables in multivariate analysis and for 1: 1 matching.

Results: Direct flow to the angiosome feeding the ulcer area was achieved in 121 legs (48%) compared with indirect revascularization in 129 legs. Foot ulcers treated with angiosome-targeted infrapopliteal percutaneous transluminal angioplasty healed better. The ulcer healing rate was mean (standard deviation) 72% (5%) at 12 months for the direct group compared with 45% (6%) for the indirect group (P<.001).