Scar tissue was removed and the gap between the rostral and caudal stumps was filled with pieces of respiratory (2WDC and 4WDC groups) or olfactory (2WDT and 4WDT groups) lamina propria (Fig. 7A, right). A piece of hemostatic sponge (Hemospon, Technew, São Paulo—SP, Brazil) was placed over the transplantation site to ensure blood homeostasis. Again, muscle and skin layers were sutured and post-operatory care was maintained

as previously described. Approximately 18 weeks after spinal cord injury, the viability of grafted tissue was demonstrated http://www.selleckchem.com/products/ABT-263.html by the presence of fusiform-shaped OECs immunoreactive for p75NTR, S-100 and GFAP at the site of spinal cord transection (Fig. 8C). RLP control grafts continued to be devoid of OECs, as confirmed by the lack of cells expressing the three markers used in the lesion area (Fig. 8D). learn more Hindlimb motor function was assessed using the BBB locomotor rating (Basso et al., 1996).

This scale is qualitative, widely used and designated to assess the functional recovery of hindlimbs after lesions in thoracic spinal cord. The score of this scale ranges from 0 (no hindlimb movement) to 21 (normal movement of the hindlimbs). In this study, BBB assessment was accomplished preoperatively (naive) and postoperatively after the SCI (at days 5, 20, 35, 50, 65, 80 post-injury for the AC and AT groups; at days 5, 20, 35, 50, 65, 80, 95 post-injury for the 2WDC and 2WDT groups; and at days 5, 20, 35, 50, 65, 80, 95, 110 post-injury for the 4WDC and 4WDT groups). For each test, rats were placed in an open-field (60 × 30 × 40 cm) for 5 min. The test session was recorded with a video camera (Sony Handycam DCR-SR88, São Paulo—SP, Brazil) to allow later analysis by a blinded Phenylethanolamine N-methyltransferase observer. The scores of the left and right hindlimbs were averaged and taken as the BBB score of each animal. At the end of behavioral analysis, rats were anesthetized as described above. An

incision was made at the T12 vertebrae level to expose the spinal cord below the SCI site. After a laminectomy, FG retrograde tracer (2% dextran tetramethylenerhodamine, Biotium Inc., Hayward—CA, USA) was injected using a stereotaxic apparatus (Insight, Ribeirão Preto—SP, Brazil) coupled to a 1 μL Hamilton syringe (Hamilton Company, Reno—NV, USA). Three injections of FG (0.05 μL, 1 min duration each) were made at midline (0.5, 0.8 and 1.5 mm deep) and 1 mm laterally (0.5, 0.8 and 1.2 mm deep) in each side of this spinal cord level (Steward et al., 2006). Post-operatory care was done as previously described. One week after the retrograde tracing injections, rats received an overdose of pentobarbital (100 mg/kg body weight, i.p., Cristália, São Paulo—SP, Brazil) and were transcardially perfused with saline solution and buffered 4% paraformaldehyde (pH 7.4) using a peristaltic pump (30 mL/min, Milan Equipamentos Científicos, Colombo—PR, Brazil).

The depth of penetration of the PBL in the double gel construct was slightly greater in the presence of fibroblasts in the lower gel layer (262 ± 10 μm vs 228 ± 13 μm; mean ± SEM, n = 3–5) but the difference was not statistically significant. Since the effects of fibroblasts on PBL migration were reduced when they were remote from

the surface, we tested whether this applied when double gels were overlaid with EC. The double gel separated the EC and fibroblasts by about 800 μm and the overall gel thickness was slightly but significantly reduced by the presence Antiinfection Compound Library concentration of fibroblasts (Fig. 6A). Under these conditions, fibroblasts induced a small but significant increase in PBL transendothelial migration (Fig. 6B), but had no effect on the initial adhesion (data check details not shown), number of PBL entering the gel, or the depth to which they penetrated (Fig. 6C,D). Taken together, the above results suggest that fibroblasts can have effects on adhesion to EC and transmigration remotely, but effects on subsequent migration in tissue are dependent on direct contact and/or modification of matrix density. In principle, the effects of fibroblasts noted above might be greater or less for different subsets of the PBL. In that case, studies of mixed populations

might yield averaged results which hide or underestimate the specific effects. We thus evaluated separately the behaviours of the main subsets within the PBL, using flow cytometry to identify them in the various collected fractions. We found in the two-filter model that fibroblasts promoted transendothelial PAK6 migration similarly for CD4 and CD8 subsets of T-cells, and that hold-up of T-cells by fibroblasts after they had migrated through EC

was also similar for these subsets (data not shown). When EC were cultured on filters over gels, we assessed B-cells as well as the CD4 and CD8 populations of T-cells (Supplemental Fig. 1). Migration through the EC in unstimulated co-cultures was higher for all three cell types when compared to mono-cultures (Fig. 7A), while no subset was affected by co-culture in the cytokine stimulated cultures (Fig. 7B). In contrast, while fibroblasts inhibited entry of the CD4 and CD8 T-cells into the underlying gel, B-cells penetrated gels containing fibroblasts nearly as well as empty gels (Fig. 7C,D). Similar observations were made in constructs formed in the absence of endothelial monolayers, where fibroblasts decreased T-cell, but not B-cell, penetration of the gel (data not shown). For the CD4 and CD8 T-cells, we also compared the behaviour of the naïve, effector memory or central memory cells. Overall, memory T-cells preferentially migrated across EC mono- and co-cultures compared to naïve T-cells (data not shown).

As shown in Fig. 2, rates of recanalization in the PROACT II study were quite similar to those obtained in the sonothrombolysis with TCCS and rtPA study. The PROACT II study randomized patients with MCA main stem or M2 branch occlusions within a 6-h time window for intra-arterial thrombolysis with pro-urokinase. The sonothrombolysis with TCCS and IV rtPA study randomized patients with proximal MCA main stem occlusions without residual flow (including patients with additional ipsilateral internal carotid artery occlusion) within a 3-h time window for 1 h of continuous insonation. As shown in Fig. 3, comparable

outcome results after 3 months (3–4 months in PROACT II) were obtained for the sonothrombolysis selleck chemical with TCCS and IV rtPA group and the pro-urokinase treatment group. The strong tendency toward a worse outcome for patients in the IV rtPA group without sonothrombolysis compared with those in the PROACT II control group may indicate that patients in the Lübeck randomized study may have been more severely affected than those in the PROACT II study. The lack of a temporal bone window is one main limitation of sonothrombolysis. Research studies have revealed that the frequency of an insufficient temporal sound

window for TCCS can vary from 8% [12] to 27% [13]. On the other hand, also the interventional therapy may not be applicable for all patients. A common limitation of interventional therapy is the lack of patency of the proximal carotid artery. www.selleckchem.com/products/SNS-032.html Data from the own register of MCA-M1 occlusions have revealed the presence of an additional proximal occlusion of the internal carotid artery in 23% of patients (unpublished data). A meta-analysis conducted by Tsivgoulis et al. [3] on sonothrombolysis with transcranial US (TCCS or TCD) included over 400 patients. They found that in comparison to patients with P-type ATPase rtPA treatment alone, patients who underwent sonothrombolysis had a 3 times higher chance for complete recanalization and a 2 times higher chance

for non-disability after 3 months. There was no evidence for increased risk of cerebral bleeding with US treatment. When the thrombolytic effect of “diagnostic” transcranial US was clinically observed for the first time, no experimental data on the effect of high-frequency, low-energy PW US on thrombolysis were available at the time. However, during the 1990s (after much time had passed since the first description of the thrombolytic effect of US in the late 1970s [14]), in vitro studies using high-frequency (1 MHz) and high-energy (spatial peak temporal average intensity [ISPTA] of 2 W/cm2) US demonstrated improved US-mediated binding of rtPA to fibrin, as well as reversible disintegration of fibrin without thrombolytics [15].

Therefore, it was considered that the amount of accumulation of bisphosphonate within bone after each single intermittent dose was more than that obtained with continuous administration. It was considerable that the amount of risedronate accumulation is higher in the 75 mg once-monthly group than in the 2.5 mg once-daily group after each single 75 mg once-monthly group treatment. Therefore, each administration of risedronate 75 mg once-monthly, which has a larger accumulation Talazoparib in bone, is possibly associated with more diffusion in bone than 2.5 mg once-daily administration. Therefore,

it may be possible that this difference of distribution in bone between daily and monthly risedronate administration causes the difference in the prevention of bone fracture, but further research is required to obtain more data. With regard to safety, the frequency of overall AEs, gastrointestinal AEs (which are typical AEs during bisphosphonate therapy), serious AEs, and the number of subjects for whom treatment was discontinued due to AEs, were comparable

in the two treatment groups. The frequency of AEs associated with gastrointestinal symptoms was similar between treatment groups. There was no notable difference in baseline demographics, complications, and medical history between subjects who http://www.selleckchem.com/products/bgj398-nvp-bgj398.html had developed AEs associated with gastrointestinal symptoms and those who had not. AEs associated with gastrointestinal symptoms developed most frequently during the period from the

initial administration to Day 30; the frequency of new onset of gastrointestinal symptoms tended to decrease thereafter in each of the treatment groups (data not presented). One of the AEs, diarrhea, was remarkable as its frequency was higher in the 75 mg once-monthly group than in the 2.5 mg once-daily group. However, the number of subjects who discontinued due to diarrhea did not differ significantly between the two treatment groups (4 and 5 subjects in the 2.5 mg once-daily and 75 mg once-monthly groups, respectively) and its severity was mild or moderate. Influenza-like illness associated with Carteolol HCl both IV and oral bisphosphonates is transitory and self-limiting and usually does not recur after subsequent drug administration. This influenza-like illness is referred to as APR [28]. In the current study, AEs potentially associated with APRs only occurred in the 75 mg once-monthly group; the incidence was low, severity was mild or moderate, and these events were not considered to be clinically important. In the multinational (ex-Japan) phase III study, AEs potentially associated with APRs occurred at a similarly low rate as in our study; 1.4% (9/650) of subjects treated with risedronate 150 mg once-monthly and 0.2% (1/642) of subjects treated with 5 mg once-daily [7].

Characteristics of interest for our study population of 81 children and adolescents are shown in Table II. The minimum and maximum ages of the participants GSK-3 phosphorylation were 0.70 and 20 years, respectively. There were 10 patients with single kidney and 7 with a kidney transplant. The primary diseases that resulted in a kidney transplant were nephropathic cystinosis (4 cases), kidney dysplasia (2 cases), and autosomal recessive polycystic kidney disease (1 case). Five patients with Wilms tumor, 1 with mesoblastic nephroma, and 1 with Langer Giedion syndrome had single native kidneys after a unilateral nephrectomy performed for clinical

care. The values of mGFR and the 14 corresponding eGFR values are shown in Table III. The mean mGFR for the 81 subjects was 77.9 ± 38.8 mL/min/1.73 m2. The median and IQR (P25, P75) were 77.8, 52.0, and 96.0 mL/min/1.73 m2, respectively. The numbers of patients with mGFR ≥90, 60–89, 30–59, and <30 mL/min/1.73 m2 were 25, 31, 17, and 8, respectively. The calculated eGFR values were highly correlated (P < 0.001) with the mGFR value. However, 3 equations based on Scr alone, 1 based on Scys, and all 4 based on combinations of both demonstrated no significant difference from the mGFR values (P > 0.05).

These same 8 equations also had lower bias compared with the others selleck compound in the Bland-Altman analysis. Table IV lists the performance of the selected 8 equations determined by calculating accuracy, bias, and precision. All had low bias, but 3 multivariate Thiamine-diphosphate kinase equations based on a combination of Scr and Scys, Schwartz et al4 and 11 and Chehade et al18 had the highest accuracy with approximately 60% of P15 and 80% of P30. Fig 1 shows the agreement between eGFR and mGFR for these 3 multivariate equations. There was good agreement across the GFR range from low to high, especially

for equations of Schwartz et al.4 and 11 On the basis of the results mentioned previously, the 3 multivariate equations had the best performance among all eGFR equations. We analyzed their applicability in 10 patients with a single kidney, 7 with kidney transplant, and 11 short stature patients with height Z-score ≤−2.5 ( Table V). From the Wilcoxon test, there was no significant difference between eGFR and mGFR in patients with single kidney, kidney transplant, and short stature (P ≥ 0.05). The values of the 3 equations also showed acceptable bias and precision in the Bland-Altman analysis. Accurate assessment of GFR is essential for interpreting the symptoms, signs, and laboratory abnormalities that may indicate kidney disease, for monitoring side effects of therapeutic drug use, and for detecting and managing CKD and assessing its prognosis, among others.

For the colour parameters crumb lightness (L*), chroma Protein Tyrosine Kinase inhibitor (C*) and hue angle (h), as expected, it was verified that wheat bran was the fibre source that had a greatest effect, due to its inherent colour Eqs. (1), (2) and (3). The increase in wheat bran reduced lightness and hue angle and increased chroma, that is, made crumb colour darker, with a more saturated colour, tending more to red (Fig. 1). equation(1) CrumbL∗=66.72−4.06WB+0.53WB2+0.47RS(R2=0.9631;Fcalc/Ftab=36.47;p<0.05) equation(2) CrumbC∗=16.66+0.49WB−0.36RS+0.24RS2−0.28LBG(R2=0.7765;Fcalc/Ftab=4.65;p<0.10) equation(3) Crumbh=78.93−4.01WB+0.54WB2−0.54RS2+0.49LBG(R2=0.9626;Fcalc/Ftab=26.29;p<0.05)

Resistant starch and LBG, considered white fibre sources, interfered less with crumb colour. Regarding lightness, resistant starch contributed to an increase in its

value, that is, tending to leave crumb lighter. LBG did not interfere with this colour parameter. For chroma, resistant starch and LBG contributed to a reduction in its value, that is, tending to leave crumb with a less saturated colour. For hue angle, the effect of these fibre sources depended on the concentration of the other sources present, as can be observed through the response surfaces generated by the model (Fig. 1). They show that, within the ranges studied, when resistant starch was used in amounts between 5-Fluoracil in vivo 4 and 16 g/100 g flour and the of amount of LBG was increased,

mainly in amounts above 1.5 g/100 g, the crumb of loaves trended more to yellow (higher h values). The values of crumb Flucloronide hue angle (h) were in the range between 73.67° and 87.62°. By these values, it can also be seen that the crumbs of all loaves were located predominantly in the first quadrant of the colour diagram, being between the axis +a (red) and +b (yellow). Comparing these results found for re-baked part-baked breads with those found for conventional breads (Almeida et al., 2013), we observed that the behaviour of wheat bran was the same for both. However, the behaviour of resistant starch and LBG changed. This could be because water migration during frozen storage and/or starch gelatinization during the two baking stages could be affected differently by the different fibre sources, having an effect on colour. The consumer profile of the panellists was the same as in our previous work (Almeida et al., 2013). The main parameters that influence food acceptance are appearance, aroma, taste and texture. If one of these factors does not meet expectance, the food will not be consumed, or, if consumed, will cause a negative response from consumers (Faridi & Faubion, 1990; Mohsenin, 1986). Through Table 2, it can be observed that the loaves produced had a good acceptance for these parameters. The consumers, in average, did not dislike any of the loaves in any of the attributes evaluated.

chem.qmul.ac.uk/iubmb/enzyme/), enzymes are classified into six main classes: oxidoreductases, transferases, hydrolases, lyases, isomerases and ligases. Hence, lipases are hydrolases. Aldol condensation, on the other hand, is carried out by lyases, aldehyde-lyases has been assigned the number 4.1.2 (Nomenclature Committee of IUBMB, 1992). However, lipases have now been shown to catalyze not only aldol condensation, but also the Mannich reaction, Michael addition, Morita–Baylis–Hillman reaction as well (Hult and Berglund, 2007, Kapoor and Gupta, 2012, Lai et al., 2010 and Li et al., 2008)! So, to start with we have a problem with

the classification. Khersonsky and Tawfik (2010) have made some suggestions in the regard. In many cases, these selleck chemical promiscuous reactions involve high catalytic efficiency which is in the same range as seen in

normal enzyme catalyzed reactions. Babtie et al. (2010) have discussed this and point out that rate accelerations (kcat/Km)/k2 of up to 1018-fold are known. In many other cases, protein engineering and directed evolution has been successfully used to induce catalytic promiscuity ( Khersonsky and Tawfik, 2010). Many of these reactions are industrially important. Large number of reports regarding catalytic promiscuity deal with reactions carried out with industrial preparations of lipases ( Busto et al., 2010 and Kapoor and Gupta, 2012). While catalytic promiscuity involves the active site of the enzyme, moonlighting RG7420 supplier by proteins can involve different parts of the enzyme molecule (Jeffery, 1999). The phenomenon of moonlighting constitutes a definite shift from the well-known one gene-one protein-one function paradigm. The different functions of a moonlighting protein can be displayed: Casein kinase 1 in two different locations in the cell (one can be even intracellular and another extracellular); by a change from the monomer to oligomer structure, in different cell

types or even with a change in ligand or substrate concentrations (Jeffery, 2009). While few examples of moonlighting involve different catalytic activities, in larger number of cases the different activities encompass non-catalytic functions like repressor, growth factor, receptor, inhibitor, chaperone and regulator activities (Jeffery, 1999, 2009). Apparently new enzymes continue to evolve. Atrazine chlorohydrolase (which degrades herbicide atrazine) has evolved (from melamine hydrolase) between 1950 and 1990 (Janssen et al., 2005). Directed evolution, of course, is being extensively used to obtain enzymes which tailored specificity (Arnold and Georgiou, 2003a and Arnold and Georgiou, 2003b). All the different phenomena and observations discussed in this section have a common message: old classification and old way of reporting data on enzyme catalyzed reactions may not be adequate. In some cases, a little tweaking of guidelines may work. Eventually, we would need to evolve new guidelines (see also Tipton et al., 2014).

Organoids as pure epithelial cultures lack tumor stroma and vasculature. In that respect, PDTX models are more physiologically

relevant and allow drug tests that target host–tumor interactions. Regarding tumor heterogeneity, organoids therefore fall in between purely clonal cancer cell lines and PDTX. Ambivalent is the requirement of matrigel which makes organoid culture more labor intense than culturing cell lines in 2D and adds a complicating parameter to potential drug screens. Then again, the laminin-rich and collagen IV-rich matrigel functions as a basement membrane substitute which, given its tumor origin [39], may be physiologically relevant. Also, organoid culture is considerably easier than maintaining PDTX. Currently available human (cancer) organoid lines are limited to the intestine. However, given recent advances buy FDA approved Drug Library in organoid cultures of several mouse tissues (stomach, liver, pancreas, and others [40, 41 and 42]) it seems merely a question of time and effort before equivalent human (cancer) organoids can be cultivated as well. A future collection of organoids that is representative of the respective cancer group, could DZNeP datasheet help patient stratification as well as oncogenic therapeutics. HC is inventor on several patent applications related to organoid culture. Papers of particular interest, published within the period of review, have been highlighted as: • of special

interest We thank Dr. M. van de Wetering for providing organoid pictures. Funding was provided by KWF/PF-Hubr 2007-3956.

“
“Current Opinion in Genetics & Development 2014, 24:82–91 This review comes from a themed issue on Cancer genomics Edited by David J Adams and Ultan McDermott For a complete overview see the Issue and the Editorial Available online 26th February 2014 0959-437X/$ – see front acetylcholine matter, © 2013 The Authors. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.gde.2013.12.004 Cancer is a disease caused by changes to the DNA, whereby the cancer genome is shaped by the interplay of processes of DNA damage and repair, cellular selection and clonal expansions [1 and 2]. Tumour evolution is classically thought of as a series of clonal expansions that are each triggered by new driver mutations conferring a selective advantage [3 and 4], hence ‘new’ cells undergo Darwinian evolution, very much like how species develop [5 and 6]. Over the past decades, we have learnt much about how cancers develop from studying their genomes, most notably through the introduction of massively parallel sequencing. Comparison of cancer samples from different sites or different time points is increasingly painting a picture of cancers undergoing branching evolution, resulting in competition between different subclones [7, 8, 9, 10, 11, 12 and 13]. In solid tumours, this picture is further complicated by a topological component [8 and 14], with potentially different selection forces operating at different locations of the tumour.

3). Total proteins were extracted from the first expanded leaves of salt-treated seedlings of T349 and Jimai 19. The profiles of wheat leaf proteins were established at a pI range of 3.5 to 10.0 and with a molecular

see more mass range of 13 to 110 kDa ( Fig. 4). Compared with Jimai 19, 17 protein spots (S1-1 to S1-17) were up-regulated in T349 ( Fig. 5), and all of these proteins were identified by mass spectrometry ( Table 3). The significant differences between Jimai 19 and T349 leaves corresponded to their different protein responses to salt stress. The functional classification analysis according to gene ontology (GO) annotations and PubMed references revealed that the proteins were clustered into several categories. Those 17 differential proteins were involved in osmotic stress, oxidative stress, photosynthesis, and lipid metabolism. Osmotic stress-related proteins include methionine synthase (S1-11) and glyceraldehyde-3-phosphate dehydrogenase (GPD) (S1-6). Oxidative stress-related proteins include NADP-dependent malic enzyme (S1-12), glutathione transferase (S1-3) and 2-cys peroxiredoxin (S1-10). Photosynthesis-related

proteins include Rubisco large subunit (RLS), Rubisco activase (S1-16) and chlorophyll a–b binding proteins (S1-9). Spots S1-7, S1-8, S1-13, S1-14, and S1-15 were all identified as Rubisco large subunits with different molecular masses and isoelectric points corresponding to their spot positions on the gel. Lipases (S1-17) Bacterial neuraminidase directly

catalyze the hydrolysis or synthesis of lipids. Spots S1-1, S1-2, S1-4, and S1-5 were identified as predicted proteins of barley. According to NCBI BLAST results, spot S1-1 (gi|326503994) Galunisertib purchase contains the region PLN00128, which is annotated as a succinate dehydrogenase (ubiquinone) flavoprotein subunit, and has 94% identity with the Triticum urartu protein succinate dehydrogenase (ubiquinone) flavoprotein subunit (sequence ID: gb|EMS46614.1|). Spot S1-2 (gi|326511988) contains the region MopB_Res-Cmplx1_Nad11, which is annotated as the second domain of the Nad11/75-kDa subunit of the NADH-quinone oxidoreductase, and has 98% identity with the T. urartu protein NADH-ubiquinone oxidoreductase 75 kDa subunit (sequence ID: gb|EMS48685.1|). Spot S1-4 (gi|326493416) contains the region PLN02300, which is annotated as lactoylglutathione lyase, and has 98% identity with the Aegilops tauschii protein lactoylglutathione lyase (sequence ID: gb|EMT08036.1|). Spot S1-5 (gi|326491885) contains the region WD40, a domain found in many eukaryotic proteins that cover a wide variety of functions, including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly. The coleoptile length, radicle length, and radicle number of the GmDREB1 transgenic wheat lines were significantly higher than those of the wild type, suggesting that the overexpression of the GmDREB1 gene improves the growth of wheat seedlings under saline conditions.

The rate of diagnosed VTE reported in this and earlier nursing home studies might underestimate the true extent of underlying disease. The reported prevalence of asymptomatic proximal

DVT (measured through ultrasound screening) was 18% in a study of patients nursed at home or in nursing homes.19 This rate is so substantial that if it approximates the true rate of underlying disease, diagnostic improvements might be expected to drive growth in DVT incidence for some time to come. Whereas residents AT13387 research buy who have VTE on admission must be managed therapeutically once they enter the nursing home, those who are at risk during residence can receive monitoring and possible interventions to prevent a VTE episode from occurring in the first place. Thus, a practical method for risk stratification, such as that proposed by Zarowitz et al,15 might be especially beneficial for LTC clinicians. A recent study in this journal of 376 residents

newly admitted or readmitted to 17 LTC facilities has shown that fully 85% of these residents met criteria for VTE prophylaxis (VTE-P) on admission.27 In the current study, we provide evidence of strong and independent association with incidence of VTE for 7 of the 20 VTE risk factors that we evaluated: stroke, acute infectious disease, congestive heart failure, obesity, hormone replacement therapy, megestrol therapy, and immobility. Although the risk for VTE has been found to increase with age, a surprising finding in the current study was the lack of evidence for age younger than

60 years as an independent predictor for VTE. Further, a large proportion ATM/ATR inhibitor clinical trial of younger residents had VTE; admission and incidence rates Thymidine kinase during residence for these younger residents were as high as or higher than those of the older age groups. These findings are likely attributable to the unique case-mix of younger nursing home residents. A closer examination of residents younger than 50 and 50 to 64 years reveals severe levels of disability, apparent with high rates of neurological disease, cardiovascular disease, diabetes, and cancer, and high overall VTE risk (multiple trauma, obesity, immobility, stroke, cancer, acute infectious disease, COPD, congestive heart failure, and megestrol use), which collectively might be acting to overcome the potential age-related risk reduction that would otherwise be observed in younger patients outside of the nursing home setting. Our study had several limitations. First, the study design does not permit delineation between new VTE events and recurrences of earlier VTE events that occurred before the start of data collection. Second, the MDS is a component of but does not encompass the full resident medical chart and may not have adequately captured emergent VTE, comorbid conditions, and VTE risk factors (eg, lower-limb orthopedic surgery).