Of those, 2,334 had NAFLD After 179 months of follow-up, the ove

Of those, 2,334 had NAFLD. After 179 months of follow-up, the overall mortality was 20% (N=467). Five most common causes of death in NAFLD were cardiovascular-respiratory diseases (41.5%),

solid organ malignancies excluding liver (21.0%), diabetes mellitus 32 (5.3%), and chronic liver diseases (3.17%). NFS was found to be independently associated with mortality: adjusted hazard ratio (aHR) = 1.361 (p<0.0001). After additional adjustment for age, the association of NFS with overall mortality remained significant (aHR=1.146, p<0.0001). Furthermore, in a series of survival analyses with different thresholds for NFS ranging from -5 to 5, we determined the best possible thresholds for NFS for the association with overall mortality. These survival analyses showed that NFS remained associated with mortality between a score of -1.80 (aHR=1.276, p=0.0498), and 1.25 (aHR=1.607, p=0.0203). The most significant JQ1 supplier association of NFS with mortality was found for a NAFLD Fibrosis score of 0.75 (aHR=1.775, p=0.0004). CONCLUSIONS: The well-established NAFLD Fibrosis Score is associated with overall mortality even after adjustment

for age. The threshold for NFS that would return the outcome with best association with mortality in NAFLD cohort is 0.75 which is close to 0.68 suggested by the authors for ruling-in fibrosis in NAFLD patients. Disclosures: Zobair M. Younossi – Advisory Committees or Review Panels: Merck, Vertex, Tibotec/J and J; Consulting: Loperamide Gilead Sciences The following

people have nothing to disclose: Maria Stepanova, Linda Henry, James N. Cooper, Shirley K. Kalwaney, Chapy Venkatesan, Alita Mishra Purpose: The aims of learn more this study were to determine the influence of excessive alcohol consumption on hepatocarcinogenesis and the risk factors for hepatocellular carcinoma (HCC) and to elucidate the utility of non-invasive predictive procedures for liver fibrosis, such as the FIB4-index, in the prediction of HCC in a large population of Japanese fatty liver patients without viral hepatitis. Methods: This was a retrospective cohort study conducted at a public hospital. Study subjects included 6,621 patients with non-alcoholic fatty liver disease (NAFLD) and 946 patients with alcoholic fatty liver disease (AFLD; daily alcohol consumption >70 g) diagnosed by ultrasonography. The median follow-up period was 5.9 years. The primary endpoint was onset of HCC. Evaluation was performed using Kaplan-Meier methodology and Cox proportional hazards analysis. Results: In NAFLD patients, there were 19 (0.29%) cases of newly diagnosed HCC, and the cumulative rates of NAFLD-related HCC were 0.05% at year 4, 0.21% at year 8, and 0.63% at year 12. In contrast, in AFLD patients, there were 18 (1.9%) cases diagnosed with HCC, and the cumulative rates of AFLD-related HCC were 0.67%, 1.89%, and 2.6%, respectively. The annual incidence of HCC was 0.05% and 0.22%, respectively.

1) 7, 8 In the current issue of Hepatology, the study by Fu et al

1).7, 8 In the current issue of Hepatology, the study by Fu et al.9 presents work describing a new Gemcitabine solubility dmso subset of CD4+ T cells: CD4+ cytotoxic T cells (CTL) in HCC. The authors evaluated CD4+ CTLs in a large series of patients with HCC and chronic hepatitis B virus (HBV) infection, and found clinically important correlations between CD4+ CTL, survival, and recurrence rates in patients with HCC. CD4+ T cells are a diverse and growing group of distinct cell subsets with different function and cytokine secretion patterns. These different CD4+ T-cell subsets:

T helper 1 (TH1), TH2, TH17, and Tregs, carry out specialized immunoregulatory functions to either enhance or inhibit immune responses. In the study by Fu et al. we learn that in addition to the more established subsets of CD4+ T cells, CD4+ CTLs also play a role in HCC immunopathogenesis. CD4+ CTLs are a population of T cells that express granzyme and perforin that are effectors in mediating the cytotoxic activity on target cells.10 CD4+ CTLs kill target tumor cells by way of HLA Class II molecules and they are also found in the circulation only in disease states including autoimmune disease or viral infections.11 The study www.selleckchem.com/products/BKM-120.html by Fu et al. provides the first report of decreased CD4+ CTLs frequency within the liver tumor tissue compared to nontumor liver regions in patients with HBV-related HCC.

The relative reductions of CD4+ CTLs within the tumor compared to nontumor areas demonstrate the immunosuppressive state of the tumor microenvironment within HCC. The finding of a CD4 T-cell subset with CTL features not only adds to the complexity of the immune infiltrate in HCC but also provides insight into the plasticity of CD4+ T cells in tumor immunity. HCC is a common, often lethal, complication that while most often emerges in the setting of cirrhosis it can occur even in the

absence of cirrhosis in chronic HBV. Most patients present with advanced tumors when treatment options are limited, despite the vigorous and early screening recommended in the American Association for the Study of Liver Diseases (AASLD) practice of guidelines.12 Early detection of HCC development is a difficult clinical challenge. Current clinical practice for HCC screening includes alpha-fetoprotein (AFP) monitoring and liver ultrasound that have limited sensitivity, as AFP levels do not reliably correlate with disease, survival, or recurrence. This substandard sensitivity underlines the need for a biomarker that is able to detect early stage HCC, tumor progression, and/or recurrence after surgical treatment. Thus, it is not unexpected that biomarker discovery is a hot topic in HCC research. Several biomarkers are under investigation in HCC, including glycipan-3, des-gamma-carboxyprothrombin, and micro-RNAs; however, none of these are sufficiently sensitive and/or specific to warrant clinical utility. The data of Fu et al.

pylori More effective identification, elimination and/or managem

pylori. More effective identification, elimination and/or management of risk factors will remain essential strategies

for reducing the incidence of peptic ulcer complications. In conclusion, the majority of patients with BPU present without dyspeptic symptoms. In contrast, even after healing of the ulcer, patients HSP inhibitor with a history of uncomplicated ulcers and ulcer symptoms have a significantly augmented symptom response to a standardized nutrient challenge test compared to patients with BPU. Lack of dyspeptic symptoms in patients with life-threatening BPU may reflect failure of augmented visceral sensation and result in them presenting later with complications rather than earlier with their primary disease. The data suggest that differences in the processing of upper gastrointestinal visceral afferents may play an important role in the clinical presentation of patients with complicated peptic ulcer. Based on our data it might be speculated that mechanisms that are involved

in the manifestation of symptoms in patients with functional dyspepsia may actually prevent the manifestation of ulcer complications as ulcers manifest check details with symptoms that trigger health care seeking and treatment before complications occur. This research has been funded by a project grant from the National Health and Medical Research Council of Australia, Grant Number 508110. Dr Montri Gururatsakul was supported by a NHMRC Postgraduate Masitinib (AB1010) Medical Scholarship. The authors would like to thank Dr Nancy Briggs for her help with Statistical analysis. No conflicts of interest exist. This

paper was presented in part as an oral presentation at Digestive Disease Week 2007, Washington, DC, May 2007. Gururatsakul M, Adam B, Liebregts T, Holloway RH, Talley NJ, Holtmann G. Differing clinical manifestations in complicated and uncomplicated peptic ulcer disease: Abdominal visceral sensory function may be a key. Gastroenterology 2007: 212: A43. “
“Madrid, Spain Adenoma and polyp detection rates (ADR and PDR, respectively) are important indicators of endoscopy quality, particularly in colorectal carcinoma screening. To assess the influence of the endoscopist’s experience on the ADR and PDR. In this study, 9635 colonoscopies were screened during a 5-year period. Only 5738 were finally analyzed due to exclusion criteria. The endoscopists were separated in three groups of experience according to the number of colonoscopies performed in the past (yearly and total). The number of polyps and adenomas, as well as the size and histology of these polyps were recorded. The ADR and PDR were similar regardless of the experience of the endoscopist, but those with more experience clearly found more polyps of less than 10 mm (P = 0.01) and of less than 3 mm (P < 0.0001). Most of the differences were due to a higher number of flat polyps detected by the experienced group.


“Spiroplasma citri was associated with a disease of


“Spiroplasma citri was associated with a disease of Ku-0059436 solubility dmso safflower characterized by stunting, yellowing, phloem discoloration and local or general necrosis in the Fars province of Iran. It was identified by ELISA using a locally produced polyclonal antiserum,

by PCR with specific primers and isolation in culture medium. The 16S rDNA restriction fragment length polymorphism patterns of safflower isolates were identical with those of the other S. citri isolates. A known isolate of S. citri from periwinkle induced stunting, yellowing, phloem discoloration and wilting in safflower seedlings when transmitted by dodder under greenhouse conditions. A primer pair designed on the basis of S. citri buy GSK2126458 plasmid was more sensitive than those based on spiralin gene or 16S rDNA for the detection of S. citri. Based on the sequence of the spiralin gene, S. citri isolates from safflower as well as other Iranian isolates were variable and grouped into two genetic clusters with 91.9–92.9% identity between groups. This is the first report of association of S. citri with a safflower disease. “
“Root rot caused by Rhizoctonia bataticola is a serious threat in cotton. Field experiments

were conducted to study the influences of intercropping system in cotton with inorganic fertilizer and two bioinoculants (Azospirillum and Pseudomonas) on root rot incidence and yield of cotton. The results revealed that among the intercropping systems, cotton intercropping with Sesbania aculeata (1 : 1 ratio) recorded the highest rhizosphere colonization of Pseudomonas fluorescens in the year 2007 and 2008 and the lowest root rot incidence of 1.40, 2.49 and 3.90; 1.02, 2.22 and 5.98% at the vegetative, check details flowering and maturity stages in the year 2007 and 2008, respectively. From nutrient management practices, integration of Azospirillum and Pseudomonas with 50% recommended dose of NPK recorded

the highest rhizosphere colonization of P. fluorescens in both years and the lowest root rot incidence of 1.40, 2.32 and 3.36; 1.07, 2.01 and 5.25% at vegetative, flowering and maturity stages in 2007 and 2008, respectively. Cotton + S. aculeata recorded the maximum number of sympodial branches (23.5 and 20.62/plant in 2007 and 2008, respectively) and the highest seed cotton yield of 2010 and 1894 kg/ha. The highest cotton equivalent yield (CEY) of 2052 and 1895 kg/ha was recorded in cotton + onion system, which was closely followed by cotton + S. aculeata system that had the CEY of 2010 and 1894 kg/ha in 2007 and 2008, respectively. The increased CEY is due to increased cost of onion compared with S. aculeata. Combined application of 100% recommended dose of NPK and bioinoculants recorded the seed cotton yield of 2227 and 1983 kg/ha and CEY of 2460 and 2190 kg/ha in 2007 and 2008, respectively. The lowest root rot incidence and increased yield in cotton + S.

13 How this is related to the autophagic stress that we describe

13 How this is related to the autophagic stress that we describe herein is not fully known, but we can speculate that both phenomena are associated. Importantly, pharmacological inhibition of autophagy enhances the proapoptotic action of EFV. A complex relationship between autophagy and apoptosis has been suggested for several xenobiotics that induced both processes (imiquimod in basal cell carcinoma31 or oridonin in HeLa cells32) and, of note, in both cases the inhibition of autophagy promoted apoptosis which is in keeping with our results. Our understanding

of the role of autophagy in liver pathophysiology, especially regarding drug-induced hepatotoxicity, is limited.33, 34 However, sequestration of several subcellular compartments has been documented in hepatocytes under check details different conditions. Autophagy may play a role in three important aspects of hepatic physiopathology: organelle turnover, balance of nutrients and energy, and removal of misfolded/damaged proteins,33 and has been recently implicated in conditions such as liver ischemia-reperfusion injury, alcohol-related liver damage, hepatitis B/C infection, hepatocellular carcinoma, and nonalcoholic

liver disease.33, 34 Interestingly, hepatocytes were an early model for mitophagy following MPT and loss of ΔΨm. Recent data suggest that autophagy facilitates cell survival in various conditions of liver injury, including drug toxicity34; mitophagy was found to reduce hepatotoxicity and steatosis associated with

buy BMS-354825 acute ethanol exposure,35 confer resistance to injury from menadione-induced oxidative stress,36 and promote survival of HepG2 cells against ginsenoside Rk1-induced apoptosis.37 Failure of this adaptive mechanism may lead to autophagic cell death. Our results add weight to this hypothesis, because Ponatinib ic50 the mitochondrial degradation detected in our model occurs as a rescue mechanism that promotes hepatic cell survival, as shown by the fact that its pharmacological inhibition leads to increased EFV-induced cell damage. Nevertheless, when a massive autophagic response is induced the degradation capacity of the cell is exceeded, and “autophagic stress” is produced. Finally, there is growing evidence of a complex role of autophagy in viral infections including HIV38 and HBV/HCV,34 which is of special relevance in the light of our results. Hepatitis coinfections are very common among HIV patients and greatly enhance the hepatic toxicity of EFV.1, 2 In addition, there is evidence of autophagy induced by several protease inhibitors.39, 40, 41 Moreover, HIV patients usually receive concurrent medications that may be potentially hepatotoxic.1 All of this provides a picture of autophagic signaling/induction in which complex interactions take place between EFV and concomitant conditions which may ultimately influence liver function.

The fossil record provides only a limited amount of certain kinds

The fossil record provides only a limited amount of certain kinds of evidence (primarily hard tissues such as skeletons and shells, and ichnites such as tracks), limiting the power of interpretations of behaviour. Palaeontologists have only a tiny amount of the data that would be available to an ethologist

studying an extant organism. Some kinds of palaeontological data are readily available, but costly or time consuming to acquire or may damage the specimens (e.g. histological thin sections of bone, or synchotron scanning of fossils). Furthermore, PI3K Inhibitor Library all fossils specimens are subject to the filter of taphonomy that can potentially profoundly alter the available data, presenting misleading pictures of the evidence (e.g. lamellibranch shells having suffered drilling from predators transport further than do intact ones, Lever et al., 1961). Detailed studies or exceptional specimens can potentially reveal much information (e.g. the potential to separate out at what time various tracks

were laid down relative to one another – Milner, 2005, evidence for transport of material – Voorhies, 1969, and to distinguish between trample marks or bite marks – Fiorillo, 1984) and support for a conjecture. However, these must be put in the context of the specimens, a correct understanding and appreciation of behaviour, and framed as a specific hypothesis. They Tyrosine Kinase Inhibitor Library cell line must also be formulated in an appropriate manner that does not immediately lead to a false premise being created. Given the limitations of palaeontological data, we would advocate that formulated hypotheses need not be testable in the present based on the then available data, but at least have the capacity to be tested on the basis of future finds or analyses. Here we outline some previous problems affecting hypotheses about palaeobehaviours. We do not intend to overtly criticize the studies cited as examples, but rather draw attention to potential pitfalls

that may have been previously overlooked. Note that not all of these examples may ultimately be incorrect; however, they are not supported by the data as suggested: (1)  False dichotomy or premise. Mutually exclusive hypotheses are useful as they allow Glycogen branching enzyme the evidence for only a single concept to be used to infer the state of another. However, such relationships must truly be antagonistic, or a false dichotomy is created and evidence for one hypothesis incorrectly used as evidence against another. For example, Taylor et al. (2010) showed that Senter’s (2007) claim of a dichotomy between sexual selection and feeding envelope increase in sauropod dinosaur necks was false. Thus Senter’s arguments in favour of sexual selection did not rule out a functional role.

In the frontal group (n = 19), 1 subject had persistent forehead

In the frontal group (n = 19), 1 subject had persistent forehead numbness (1 year

postoperatively), 1 subject had asymmetric eyebrow elevation, and 1 subject appreciated residual function of the corrugator supercilii. In the temporal group (n = 19), 10 subjects experienced temporal hollowing, 2 subjects experienced intense pruritis, and 1 subject experienced temporal hair loss/thinning. In the occipital group (n = 11), 1 patient experienced neck stiffness (1 year postoperatively). Interestingly, only 2 of the adverse events were specifically cited to last for greater than 1 year, which would lead some readers to assume that the other events lasted for less than 1 year and resolved when in fact some of these adverse events may actually be ongoing. Other complications of the intervention noted in the literature include cutaneous hypersensitivity, neck

weakness, and facial nerve injury.[6] Midostaurin mw LY294002 molecular weight The author attributes some of the improvement in the sham surgery group at 1 year after surgery to the placebo effect. To expand on the power of sham procedures, the author references a sham intervention placebo effect noted in an acupuncture trial involving 37 subjects who received either 16 real or sham acupuncture treatments over 3 months. These subjects experienced similar reductions in migraine frequency regardless of receiving sham or actual acupuncture.[26] It is interesting that the author references

a sham procedure placebo effect for acupuncture, which has weak evidence for migraine prevention, to support the high placebo effect for another procedure with weak evidence such as surgical deactivation Glutathione peroxidase of migraine headache trigger sites. The author also suggests that the subjects in the sham surgery group provided exaggerated preoperative data to increase their chance of selection, which would also improve outcomes in the placebo group. This is a great argument to nullify any control group in any study if there is gain to be made by promoting the actual intervention. The author then attempts to oversimplify and discredit the trigeminovascular theory of migraine by claiming that the literature is unclear whether migraines are caused by cortical neuronal hyperexcitability, cortical spreading depression, peripheral activation/sensitization, central activation/sensitization, abnormal modulation of brain nociceptive systems due to dysfunction of the periaqueductal gray matter, or changes in the meningeal vasculature.[7] The reality is that these different mechanisms that the author attempts to single out as a potential cause of migraine are likely different events that occur in sequence leading up to a migraine. Migraine is a complex genetic disorder with susceptibility likely arising from one or more variants in the genetic code.

The sensitivity, specificity, positive predictive value, and nega

The sensitivity, specificity, positive predictive value, and negative predictive value of CT scan for the detection

of FB was 98.2%, 90.1%, 96.5%, and 94.7%, respectively. Conclusion: Pre-endoscopic CT scan is accurate and noninvasive diagnostic modality for the detection of ingested esophageal FB. Moreover, CT scan prior to endoscopic procedure is very useful to avoid unnecessary endoscopic procedure. Further studies are BAY 80-6946 needed about the advantages of pre-endoscopic CT scan for the evaluation of pre-endoscopic complication and for the planning of endoscopic removal method. Key Word(s): 1. Computed tomography; 2. endoscopy; 3. esophageal foreign body; 4. fish bone

Presenting Author: ZHIFANG JIA Additional Authors: JING JIANG, XUEYUAN CAO, DONGHUI CAO Corresponding Author: XUEYUAN CAO Affiliations: First Hospital of Jilin University, First Hospital of Jilin University, First MLN0128 Hospital of Jilin University, Objective: CD24 expression has been reported to mediate gastric carcinogenesis and correlate with poor prognosis. The aim of this study was to evaluate the role of SNPs of CD24 gene in susceptibility and prognosis of gastric cancer. Methods: Three loci of CD24 gene, P-534, P170 and P1527, were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 679 histologically-confirmed gastric cancer cases, 111 gastric atrophy cases and 976 tumor-free controls. CD24 expression was evaluated by a tissue microarray immunohistochemistry method in 131 gastric cancer specimens. Serum anti-Helicobacter pylori (H.pylori) IgG were detected by enzyme-linked Miconazole immunosorbent assay (ELISA). Results: All of the three loci

were in Hardy-Weinberg equilibrium in the control group. None of the three SNPs was observed to be associated with the risk of gastric cancer or gastric atrophy. And no SNPs were found to be correlated with the TNM stage, tumor differentiation, lymph node metastasis and overall survival of gastric cancer. Moreover, no difference of CD24 expression was found among the three genotypes of each SNP. Conclusion: SNPs of CD24 gene may not be correlated with the risk and prognosis of gastric cancer. However, more studies may be needed to confirm the conclusion. This work was supported by Norman Bethune Program of Jilin University [2013025], National Natural Science Foundation of China (81072369 and 81273065). Key Word(s): 1. Polymorphisms; 2. CD24 gene; 3. prognosis; 4.

This

This selleck products study showed that the area under the receiver operating characteristic curve for the total CK-18 prediction of a liver fibrosis stage ≥ F2 was 0.73, which is similar to the values reported for various assays based on multiple putative fibrosis biomarkers.9 This proves that a single good biomarker of liver epithelial

death (total CK-18) provides a fairly robust readout of liver fibrosis, which is a complex injury response presumably captured by the other assays. This suggests that an active liver injury (often subclinical) is the main force perpetuating liver fibrosis in most individuals and provides a reason for optimism because it supports the dynamic nature of fibrogenesis/fibrinolysis and the inherent reversibility of liver fibrosis. Like more complex assays, the total CK-18

ELISA reliably differentiates advanced fibrosis from no fibrosis, but it is less discriminating at lower fibrosis stages; this reflects the dynamic nature of fibrosis and the fact that no available assay captures both sides of the fibrosis equation. Total CK-18 assays measure the predominant liver fibrosis stimulus (i.e., liver epithelial cell death), whereas other assays largely reflect Trichostatin A manufacturer various aspects of the resultant wound-healing response. The use of both stimulus and response assays might provide complementary/additive information that could perfect the noninvasive staging of fibrosis. In other words, combining an assessment of the strength of the fibrosis stimulus (CK-18) with an estimate of the intensity of the fibrogenic response (fibrosis markers or elastography) might permit individuals with given levels of liver cell death to be stratified into groups of hyporesponders, normoresponders, and hyperresponders with respect to wound healing. Additional power might be obtained by

the serial acquisition of such information from given individuals. Further research is needed to test and refine these concepts. Success offers exciting opportunities for personalizing liver disease management and facilitating the discovery of effective antifibrotic therapies. “
“Background and Aim: Endoscopic forceps biopsy (EFB) as the primary histological ifenprodil diagnosis of gastric epithelial neoplasia (GEN) is debated in the era of endoscopic resection (ER). Our aim was to investigate the diagnostic reliability of EFB in patients with GEN compared to ER specimens as the reference standard for the final diagnosis in a large consecutive series. Methods: This was a cross-sectional retrospective study at a tertiary-referral center. A total of 354 consecutive patients with 397 GENs underwent ER (endoscopic mucosal resection or endoscopic submucosal dissection).

Results:  On T1-weighted images of the porcine liver, the RF abla

Results:  On T1-weighted images of the porcine liver, the RF ablated lesions showed hyperintense

regions with hypointense rims, which histopathologically corresponded to sinusoidal congestion. The Gd concentrations in ablated regions in group A were significantly higher than those in non-ablated regions, while the concentrations in both regions in group B fell to nearly undetectable levels. In 27 of the 28 HCC nodules, the treated area consisted of a hypointense region, indicative of the tumor, and a surrounding hyperintense rim 2 h after ablation. Subsequently, a thin hypointense find more region was observed in the outermost layer 24 and 72 h after ablation. Conclusion:  Administration of Gd-EOB-DTPA in conjunction with RF ablation of HCC may be feasible for the assessment of an accurate ablative margin. “
“Instant oatmeal has been proposed as a good alternative to the standardized low-fat egg white test meal for gastric emptying studies. We aim to establish normal values of oatmeal-based

gastric emptying scintigraphy and test its Selleckchem Temsirolimus correlation with gastroparesis symptoms in the Chinese population. This study prospectively enrolled 60 healthy volunteers, 30 functional dyspepsia and 30 diabetes patients with gastroparesis symptoms. All participants were evaluated using the Gastroparesis Cardinal Symptom Index. Each participant ingested instant oatmeal mixed with 1 mCi of 99mTc diethylenetriaminepentacetic acid, and serial imaging was immediately

acquired for 3 h in the supine position using a left anterior oblique projection. Time-activity curves were generated and quantitative parameters were determined. Normal values were established from healthy volunteers and further applied in the symptomatic patients. All participants finished the test meal and tolerated the procedure well. All gastric emptying parameters were not significantly affected by age or gender. Values above the 95th not percentile of T1/2, gastric retention at 1, 2, and 3 h (85 min, 65%, 28%, and 8%, respectively) were indicative of delayed gastric emptying. Values below the 5th percentile of gastric retention at 0.5 and 1 h (40% and 15%, respectively) were indicative of rapid gastric emptying. The lower gastric retention limit at 0.5 and 1 h were 40% and 15%, respectively. Four (13.3%) diabetes and four (13.3%) functional dyspepsia patients had delayed emptying while three diabetes patients (10%) had rapid emptying. Gastric emptying parameters correlated best with vomiting (r = 0.621) and nausea (r = 0.566) in diabetes patients. We established normal values of oatmeal-based gastric emptying scintigraphy and observed good correlation with cardinal gastroparesis symptoms in the Chinese population. “
“Polycystic liver disease may complicate autosomal dominant polycystic kidney disease (ADPKD), a disease caused by mutations in polycystins, which are proteins that regulate signaling, morphogenesis, and differentiation in epithelial cells.