\n\nMethods: Sixty-two patients with medication-resistant AVH were randomized

over three conditions: rTMS targeted at the area of maximal hallucinatory activation calculated from individual fMRI scans during AVH, rTMS directed at the left TP, and sham treatment. Repetitive TMS was applied during 15 sessions of 20 min each, at 1 Hz and 90% of the individual motor threshold. The severity of AVH and other psychotic symptoms were monitored during treatment and 3-month follow-up, with the Auditory selleck chemical Hallucination Rating Scale, the Positive and Negative Syndrome Scale, and the Psychotic Symptom Rating Scales.\n\nResults: The effects of fMRI-guided rTMS and left TP rTMS on the severity of AVH were comparable to those of sham treatment. No differences in severity of general psychotic symptoms were found among the three treatment click here conditions.\n\nConclusions: Low-frequency rTMS administered to the left TP or to the site of maximal hallucinatory activation is not more effective for medication-resistant AVH than sham treatment.”
“During recent decades the prevalence of IgE-mediated (atopic) allergic diseases in Western Europe and the USA has been increasing dramatically. It has been suggested that one possible cause is the presence in the environment of chemicals that may act as adjuvants, enhancing immune and allergic

responses. Certain commonly used phthalate plasticizers such as butyl benzyl phthalate BMS-754807 nmr (BBP) have been implicated in this way. In the current experiments, the impact of BBP, applied by a physiologically relevant exposure route, on the vigour of immune responses induced in BALB/c strain mice has been examined. Mice were immunized via subcutaneous injection with the reference allergen ovalbumin (OVA) and received concurrent topical treatment with doses of BBP that induced significant changes in liver weight. The generation of specific anti-OVA IgE and IgG1 antibodies was measured by passive

cutaneous anaphylaxis and by enzyme-linked immunosorbant assays, respectively. Topical administration of BBP was without impact on anti-OVA IgE antibody responses, regardless of whether BBP was applied locally or distant to the site of OVA immunization. However, same-site treatment with high-dose BBP (100 mg) did result in a modest elevation in anti-OVA IgG1 antibody production, a subclass of antibody used as a surrogate marker of IgE responses. Taken together with human exposure data, these results suggest that the doses of phthalate encountered in the home environment are unlikely to be a major factor contributing to the increased incidence of asthma and allergy in the developed world. Copyright (C) 2008 John Wiley & Sons, Ltd.”
“One of the two principal hypotheses put forward to explain the primary magnetoreception event underlying the magnetic compass sense of migratory birds is based on a magnetically sensitive chemical reaction.

(C) 2012 Elsevier B.V. All rights reserved.”
“MAHONY PH, MYERS JA, LARSEN PD, POWELL DMC, GRIFFITHS RE Symptom-based categorization of in-flight Geneticin inhibitor passenger medical incidents. Aviat Space Environ Med 2011; 82:1131-7.\n\nIntroduction: The majority of in-flight passenger medical events are managed by cabin crew. Our study aimed to evaluate the reliability of cabin crew reports of in-flight medical events and to develop a symptom-based categorization system. Methods: All cabin crew in-flight

passenger medical incident reports for an airline over a 9-yr period were examined retrospectively. Validation of incident descriptions were undertaken on a sample of 162 cabin crew reports where medically trained persons’ reports were available for comparison using a three Round Delphi technique and testing concordance using Cohen’s Kappa. A hierarchical symptom-based categorization system was designed and validated. Results: The rate was 159 incidents per 10(6) passengers carried, or 70.4/113.3 incidents per 10(6) revenue passenger kilometres/miles, respectively. Concordance between cabin crew and medical

reports was 96%, with a high validity rating (mean 4.6 on a 1-5 scale) and high Cohen’s Kappa (0.94). The most common in-flight medical events were transient loss of consciousness (410/0), nausea/vomiting/diarrhea (19.5%), and breathing difficulty (16%). Discussion: Cabin crew records provide reliable data regarding in-flight passenger medical incidents, complementary to diagnosis-based systems, and GSK3326595 solubility dmso click here allow the use of currently underutilized data. The categorization system provides a

means for tracking passenger medical incidents internationally and an evidence base for cabin crew first aid training.”
“The stimulant designer drug mephedrone is a derivative of cathinone – a monoamine alkaloid found in khat – and its effect resembles that of 3,4-Methylenedioxymethamphetamine (MDMA). Abuse of mephedrone has been documented since 2007; it was originally a legal high’ drug, but it has now been banned in most Western countries. Using cDNA-expressed CYP enzymes and human liver microsomal preparations, we found that cytochrome P450 2D6 (CYP2D6) was the main responsible enzyme for the in vitro Phase I metabolism of mephedrone, with some minor contribution from other NAPDH-dependent enzymes. Hydroxytolyl-mephedrone and nor-mephedrone were formed in vitro, and the former was purified and identified by nuclear magnetic resonance (NMR). In four forensic traffic cases where mephedrone was detected, we identified hydroxytolyl-mephedrone and nor-mephedrone again; as well as 4-carboxy-dihydro-mephedrone, which has been previously described; and two new metabolites: dihydro-mephedrone and 4-carboxy-mephedrone. Fragmentation patterns for all detected compounds were determined by a UPLC-QTOF/MSE system, and a fragmentation pathway via a conjugated indole structure was proposed for most of the metabolites.

thaliana PLD gene transcript level. As indicators of membrane damage, electrolyte leakage and malondialdehyde contents increased significantly and peaked at hour 36 and then decreased when A. thaliana callus was treated by leukamenin E. The contents of osmotic

adjustment components proline and soluble sugar also shared similar trends. These results demonstrated that the specific mechanism of the A. thaliana response to leukamenin E was linked to PLD.”
“Introduction: Acute hypercapnic respiratory failure (AHRF) is a serious condition observed in some patients with sleep apnea-hypopnea syndrome (SANS). The objective of the present study was to study the clinical characteristics of SAHS patients who develop AHRF and their prognosis.\n\nPatients and method: A total of 70 consecutive AC220 SAHS patients who survived an AHRF episode and 70 SANS patients paired by age with no previous history of AHRF were prospectively studied and followed up for 3 years.\n\nResults: The deterioration of lung function due to obesity or concomitant chronic obstructive pulmonary diseases (COPD) was common in SAHS patients with AHRF. In the multivariate analysis, the risk factors associated with AHRF were baseline PaO2. the theoretical percentage value of the forced vital capacity, alcohol consumption,

and benzodiazepines. The mortality during follow up was higher among patients who had AHRF than in the control group. The main cause of death was respiratory, and the PND-1186 clinical trial coexistence of COPD was identified as a mortality risk factor.\n\nConclusions: The development of AHRF in SANS

patients is associated with a deterioration in lung function and with alcohol and benzodiazepine consumption. The patients had a higher mortality after the Selleck Acalabrutinib AHRF episode, mainly a respiratory cause. New studies are required that evaluate the different available therapeutic options in these patients. (C) 2010 SEPAR. Published by Elsevier Espana, S.L. All rights reserved.”
“The monitoring of insect pests in fields of forage maize is difficult because plants are tall and grow at a high density. We investigated the effectiveness of colored sticky traps and appropriate conditions for monitoring insect pests in forage maize fields. Large numbers of the maize orange leafhopper, Cicadulina bipunctata Melichar (Hemiptera: Cicadellidae), and the small brown planthopper, Laodelphax striatellus Fallen (Hemiptera: Delphacidae), were collected during the experimental period with yellow and blue sticky traps placed in summer crop forage maize fields. A greater number of insects were trapped in yellow traps relative to blue traps. Traps located at a lower height (40 cm above the ground) attracted larger numbers of C. bipunctata, whereas L. striatellus did not demonstrate a height-dependent preference. These results indicated that yellow-colored sticky traps located at low height are effective for collecting C. bipunctata and L. striatellus simultaneously.

It is thought that TI induced a short term reduction in ventilatory efficiency, which appeared to be countered by a series of compensatory mechanisms that include increased ventilation rates, and maintenance of the primary stress response. TI remains one of the most enigmatic areas of biology for all taxa and further research into its underlying psychological, physiological

and neurological processes is recommended. (C) 2011 Elsevier BM. All rights reserved.”
“Nausea and vomiting in pregnancy is a continuum that ranges from mild discomfort to significant morbidity. Systematic assessment with the use of the Pregnancy-Unique Quantification this website of Emesis/Nausea (PUQE) index and timely treatment using evidence-based protocols can decrease the time that many women spend using treatment recommendations that are inadequate. This article reviews the epidemiology

of nausea and vomiting in pregnancy, use of the PUQE index, and the evidence for specific nonpharmacologic and pharmacologic treatment regimens. A protocol for clinical management is presented. J Midwifery Womens Health 2009; 54: 430-444 (C) 2009 by the American College of Nurse-Midwives.”
“DeLong, J. M., Hodges, D. M., Prange, R. K., Forney, C. F., Toivenon, P. M. A., Nutlin-3 price Bishop, M. C., Elliot, M. L. and Jordan, M. A. 2011. The unique fatty acid and antioxidant composition of ostrich fern (Matteuccia struthiopteris) fiddleheads. Can. J. Plant Sci. 91: 919-930. The purpose of this study was to investigate the health-promoting composition of ostrich fern (Matteuccia struthiopteris) fiddlehead tissue by focussing on its fatty acid and antioxidant content and antioxidant activity. The curled crosiers (fiddleheads)

were harvested following emergence and before 10 cm growth from eight or nine sites in eastern Canada during 2008 and 2009. The crosiers were then refrigerated or kept on ice until cleaned, subsequently frozen in liquid nitrogen, and then stored at -85 degrees C. All tissue samples (except those used for ascorbate analysis) were freeze-dried, ground in a ball mill and stored at -80 degrees C until analyzed. The current study showed that fiddlehead tissue had an unusual BVD-523 cell line fatty acid composition including gamma-linolenic, dihomo-gamma-linolenic, arachidonic and eicosapentanoeic acids. The concentration of the antioxidant compounds ascorbic acid [3.0 mu mol g(-1) dry weight (DW)], alpha- and gamma-tocopherol (314 and 80.8 mu g g(-1) DW, respectively) and alpha- and beta-carotene (43.8 and 122 mu g g(-1) DW, respectively) and the xanthophyll pigments violaxanthin (225 mu g g(-1) DW), zeaxanthin (127 mu g g(-1) DW) and lutein (238 mu g g(-1) DW) ranged from high to very high for green plant tissue. The phenolic compound content (51.6 mg gallic acid equiv.

Here we provide an overview of techniques that may

be used to produce and characterize reasonably well-defined CHOS fractions. We also present possible medical applications of CHOS, including tumor growth inhibition and inhibition of T(H)2-induced inflammation in asthma, as well as check details use as a bone-strengthener in osteoporosis, a vector for gene delivery, an antibacterial agent, an antifungal agent, an anti-malaria agent, or a hemostatic agent in wound-dressings. By using well-defined CHOS-mixtures it will become possible to obtain a better understanding of the mechanisms underlying these bioactivities.”
“Acute aortofemoral graft occlusion is often effectively treated with endovascular therapy but a substantial proportion of patients experience failure or complications of this therapy, and most of them require definitive surgery for the underlying inflow, outflow, or graft disease. selleck chemical We describe a case of an aortofemoral graft occlusion that was successfully treated with the Trellis thrombectomy-thrombolysis system (Covidien, Dublin, Ireland). Subsequent stenting of the graft obviated the need for a definitive

graft revision surgery. The Trellis system combines mechanical and local pharmacologic lysis of the thrombus, with more rapid and more effective thrombus dissolution and theoretically less risk of systemic dispersion of the thrombolytic agent and less bleeding. (C) 2010 Wiley-Liss, Inc.”
“Aim:\n\nThe aim of this prospective study was to compare diagnosis, severity of trauma

and treatment of traumatic injuries to the primary dentition in two groups of children, the first recommended for treatment by general Volasertib practitioners and the second referred for treatment by a specialist paediatric dentist.\n\nMaterials and methods:\n\nA total of 323 children with traumatic injuries, 184 boys and 139 girls aged 7-83 months, participated in the study. All the children had first presented at a Public Dental Service clinic where they were examined by general dentists who decided, based on the severity of the trauma, to assign each child to one of the following two groups: Group A – recommended for treatment at the general practise (166 children with 257 traumatized incisor teeth). Group B – recommended for referral to a specialist in paediatric dentistry (157 children with 261 traumatized incisor teeth). Even in Group A, the specialist controlled the treatment decisions. The clinical diagnose and follow-up followed the recommendations presented by Andreasen & Andreasen.\n\nResults:\n\nThe distribution of trauma by age was similar in both groups, with about 60% occurring between 1 and 3 years. More injured teeth were extracted in children in Group B (n = 111) than in Group A (n = 33). A higher percentage of intruded primary incisors were recorded in Group B (24%) compared with Group A (16%).

This is a rapid assay that is suitable for the analysis of cervical samples. The proportion of cancer samples with methylated E2BS1, E2BS2, and Sp1-binding site CpGs was 47%, whereas the vast majority of samples diagnosed as being within normal limits, low-grade squamous intraepithelial lesions (LSIL), or high-grade squamous intraepithelial lesions (HSIL) harbored unmethylated CpGs. Methylation levels varied PLX4032 in vivo widely, since some cancer

samples harbored up to 60% of methylated HPV16 genomes. A pyrosequencing approach was used as a confirmation test and highlighted that quantitative measurement of methylation can be achieved by HRM-PCR. Its prognostic value deserves to be investigated alone or in association with other biomarkers. The reliability of this single-tube assay offers great opportunities for the investigation of HPV16 methylation in other HPV-related cancers, such as head and neck cancers, which are a major public health burden.”
“Study aim: Many quality-of-life assessment tools are not feasible in palliative care settings because of the severe impairment of the physical, cognitive, and psychological status of patients. This study investigated whether comprehensive instruments can Vorinostat be replaced by a single item concerning the well-being of patients.\n\nMethods: From April to December 2008 patients receiving

palliative care in three different settings (palliative care unit, inpatient unit of the department

of radiotherapy, inpatient hospice) were asked to Buparlisib chemical structure answer the assessment tools Functional Assessment of Chronic Illness Treatment (FACIT-G), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30), Schedule for the Evaluation of the Individual Quality of Life (SEIQoL), and the Minimal Documentation System (MIDOS) including a single item on well-being. Correlations of sum and specific domain scores were used for correlational analysis.\n\nResults: Datasets of 72 patients were collected. The MIDOS single item on well-being correlated significantly with the QoL indexes of the EORTC (Spearman rank correlation r = -0.563) and FACIT-G (0.527). SEIQoL had low to moderate correlations with the other assessment tools. Subscales on physical functioning from the FACIT-G (r = 0.583) and the EORTC-QLQ-C30 (r = 0.385) had the highest correlation with the single item on well-being. Well-being correlated higher with nonphysical subscales of the QoL instruments for patients in the palliative care unit than in the radiotherapy department.\n\nConclusions: The single item is unable to completely replace comprehensive questionnaires, but it is useful to initiate communication on QoL and can be recommended as a substitute for physical-functional aspects of QoL assessment in the palliative care setting.

The focus was on genes related to cell-cell contacts. Furthermore, the effect of epidermal growth factor (EGF) on gene expression was studied. Most of the genes investigated here were down-regulated in migratory cells. Many of the alterations are expected to affect the permeability

of tight junctions. Also the nectin-afadin complex of adherens junctions was https://www.selleckchem.com/HIF.html modulated as well as the expression of both the chemokine receptor CXCR4 and the EGF receptor. Of note, restitution was not accompanied by the epithelial-mesenchymal transition (EMT). EGF treatment severely affected the expression of genes important for cell-cell contact and cell communication such as selected tight junction components, CXCR4, and TFF3. Many of these genes are known to be involved in EMT and metastasis. Of special note, most of the expression changes induced by EGF are in contrast to the changes observed in migratory cells. Copyright (C) 2010 S. Karger AG, Basel”
“We have previously demonstrated

that lipoplex, a complex of cationic liposomes and DNA, could be targeted to human hepatic cells in vitro and in vivo by conjugation with bio-nanocapsules (BNCs) comprising hepatitis B virus (HBV) surface antigen L protein particles. Because the BNC-lipoplex complexes were endowed with the human hepatic cell-specific infection https://www.selleckchem.com/products/MK-1775.html machinery from HBV, the complexes showed excellent specific transfection efficiency in human hepatic cells. In this study, we have found that polyplex (a complex of polyethyleneimine (PEI) and DNA) could form stable complexes with BNCs spontaneously. The diameter and zeta-potential of BNC-polyplex complexes are about 240 nm and +3.54 CA4P cell line mV, respectively, which make them more suitable for in vivo use than polyplex alone. BNC-polyplex complexes with an N/P ratio (the molar ratio

of the amine group of PEI to the phosphate group of DNA) of 40 showed excellent transfection efficiency in human hepatic cells. When acidification of endosomes was inhibited by bafilomycin A1, the complexes showed higher transfection efficiency than polyplex itself, strongly suggesting that the complexes escaped from endosomes by both fusogenic activity of BNCs and proton sponge activity of polyplex. Furthermore, the cytotoxicity is comparable to that of polyplex of the same N/P value. Thus, BNC-polyplex complexes would be a promising gene delivery carrier for human liver-specific gene therapy. (C) 2012 Elsevier Ltd. All rights reserved.”
“Atherosclerosis (AS) causes cardiovascular disease, which leads to fatal clinical end points like myocardial infarction or stroke, the most prevalent causes of death in developed countries. An early, noninvasive method of detection and diagnosis of atherosclerotic lesions is necessary to prevent and treat these clinical end points.

\n\nMethods: This analysis is based on the prospective database of the Swiss Association of Laparoscopic and Thoracoscopic Surgery. All patients undergoing emergency laparoscopic appendectomy for acute appendicitis from 1995 to 2006 were included. The following outcomes were assessed for each of the 12 years: conversion rates, intraoperative complications, surgical postoperative complications, general postoperative complications, rate of reoperations, and length of hospital stay. Unadjusted and risk-adjusted multivariable analyses were performed. Statistical significance was set at a level of P < 0.05.

All statistical tests were 2-sided.\n\nResults: Data from 7446 patients undergoing laparoscopic appendectomy for acute appendicitis were prospectively collected. Over the period of observation, the conversion rate decreased significantly from 2.2% to 1.2% (P(trend) < 0.001), as did intraoperative GSK923295 chemical structure complications (from 3.1% to 0.7%; P(trend) < 0.001), surgical postoperative complications (from 6.1% to 1.9%; P(trend) < 0.001), general postoperative complications (from 4.9% to 1.5%; P(trend) < 0.001), and rates of reoperations (from 3.4% to 0.7%; P(trend) < 0.001). Average postoperative length of hospital stay also significantly decreased

from 4.9 to 3.5 days (P(trend) < 0.001).\n\nConclusions: Our investigation provides compelling evidence that intraoperative complications, surgical and general postoperative complications, conversion rates, rates of reoperations, and average length of hospital stay have

significantly decreased over the check details past decade in patients undergoing surgery for acute appendicitis. The present trend analysis is the first one in the literature encompassing more than a decade and reporting clinical outcomes after laparoscopic appendectomy for acute appendicitis, which represents an important quality control.”
“Objective: Psychomotor impairment has been described in hypertyrosinemia types II and III (HT III). Only recently cognitive deficits have also been reported selleck chemical in hypertyrosinemia type I (HT I). The pathogenic mechanisms responsible are unknown. Since implementation of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC, Nitisinone (Swedish Orphan International)) in the treatment of HT I, plasma tyrosine elevation is a common finding as known from the other hypertyrosinemias.\n\nPatients and methods: With elevated tyrosine as suspected pathogenic factor in the development of cognitive deficits, we here investigated tyrosine in the cerebrospinal fluid (CSF) and serotonergic and dopaminergic neurotransmitter levels in three patients with HT I during long-term treatment with Nitisinone. In addition, Nitisinone concentrations in plasma and CSF were measured. We also assessed psychomotor and cognitive development by standardized test systems and brain morphology by magnetic resonance imaging.

The average follow-up was 30.1 months. The average period from the original arthroplasty to the arthrodesis was 49.8 months. Results: Thirteen of the ZD1839 manufacturer 17 ankles were considered radiographically healed after the first attempt in an average time of 3.7 months and 3 after repeat arthrodesis.

Bone grafts were used in 16 patients. The median postoperative AOFAS score was 74.5. The mean Meary angle of the hindfoot was 5 degrees of valgus. Conclusion: Tibiotalar and tibiotalocalcaneal arthrodeses were effective salvage procedures for failed TAR. Massive cancellous allografts were a good alternative to compensate for the large bone defect after removal of the prosthesis and to preserve the leg length. Level of Evidence: Level IV, retrospective case series.”
“SETTING: The risk of pulmonary tuberculosis (PTB) may increase with increased use of anti-tumour necrosis factor (TNF) treatment in inflammatory arthritis. OBJECTIVE: To evaluate the impact of anti-TNF treatment on radiological manifestations of PTB. METHOD: Between January 2007 and December 2012, the chest radiographs (CXRs) of 23 consecutive patients with newly diagnosed PTB who underwent anti-TNF treatment were studied. Chest computed DMH1 tomography (CT) images were available for 14. To compare the radiological features

of PTB, the CXRs of 46 immunocompetent PTB patients with similar demographics were studied as controls, of whom 34 underwent chest CT. Two radiologists and one chest physician reviewed the chest images independently. RESULTS: Compared with the controls, fibronodular

lesions were less common on Alvespimycin chemical structure CXR in the anti-TNF group (P smaller than 0.001). In contrast, lymphadenopathy (P smaller than 0.001), pleural effusion (P = 0.015) and pericardial effusion (P = 0.02) were more common, while tree-in-bud appearance (P = 0.017) was less commonly depicted on chest CT in the anti-TNF group. Although there was no significant difference in zonal predilection and laterality of the lesions between the two groups, diffuse lesions (P = 0.004) on chest CT scans were more frequent in the anti-TNF group. CONCLUSION: Unusual presentations of PTB were more common in the CXRs and/or CT scans of patients who underwent anti-TNF treatment.”
“Following injury, platelets rapidly interact with the exposed extracellular matrix (ECM) of the vessel wall and the surrounding tissues. Hyaluronan (HA) is a major glycosaminoglycan component of the ECM and plays a significant role in regulating inflammation. We have recently reported that human platelets degrade HA from the surfaces of activated endothelial cells into fragments capable of inducing immune responses by monocytes.

Diets contained Selleckchem GDC-973 wheat flour as whole soft white, refined soft white, whole hard red, or refined hard red. Feeding was begun 10 days prior to carcinogen treatment and continued for 9 wk. Hard red-fed groups had significantly fewer ACF than soft white-fed groups (25-32% reduction, P = 0.013). However, state of refinement had no significant effect on ACF number. Cecal contents supernatant oxygen radical absorbance capacity and fecal bile acid concentration were significantly greater in whole wheat-fed groups than refined wheatfed groups and did not correlate with ACF number (increase of 21-22%, P smaller than 0.001 and 55-56%, P smaller than 0.001, respectively).

Consequently, wheat class, not state of refinement, appears to influence colon cancer risk, with hard red wheat protective relative to soft white wheat. Thus, epidemiological associations of reduced colon cancer risk with whole grain consumption may actually reflect different

wheat classes.”
“We derive a phase diagram buy Stem Cell Compound Library for amorphous solids and liquid supercooled water and explain why the amorphous solids of water exist in several different forms. Application of large-deviation theory allows us to prepare such phases in computer simulations. Along with nonequilibrium transitions between the ergodic liquid and two distinct amorphous solids, we establish coexistence between these two amorphous solids. The phase diagram we predict includes a nonequilibrium triple point where two amorphous phases and the liquid coexist. Whereas the amorphous solids are long-lived and slowly aging glasses, their melting can lead quickly to the formation of crystalline ice. Further, melting of the higher

density amorphous solid at low pressures takes place in steps, transitioning to the lower-density glass before accessing a nonequilibrium liquid from which ice coarsens.”
“De HSP inhibitor novo sequencing is an important computational approach to determining the amino acid sequence of a peptide with tandem mass spectrometry (MS/MS). Most of the existing approaches use a graph model to describe a spectrum and the sequencing is performed by computing the longest antisymmetric path in the graph. The task is often computationally intensive since a given MS/MS spectrum often contains noisy data, missing mass peaks, or post translational modifications/mutations. This paper develops a new parameterized algorithm that can efficiently compute the longest antisymmetric partial path in an extended spectrum graph that is of bounded path width. Our testing results show that this algorithm can efficiently process experimental spectra and provide sequencing results of high accuracy.”
“The intrauterine environment can impact the developing infant by altering the function of the placenta through changes to the epigenetic regulatory features of this tissue.