Tariot et al65 assessed the efficacy, safety, and tolerability of carbamazepine in the treatment of agitation and aggression associated with severe dementia in a placebocontrolled trial. Clinical Global Impression (CGI) ratings showed global improvement, in 77% of the patients taking carbamazepine and 21 % of those taking placebo. The mean daily dose of carbamazapine at week 6 was 304 mg/day (SD=119) with a mean serum level of 5.3 ug/mL. The drug was generally well tolerated. Divalproex sodium with an average dose at week 6 of 826 mg/day (375–1.375 mg/day with an average level of 45 μg/mL) has been shown superior to placebo (reduced agitation on the Inhibitors,research,lifescience,medical CGI in 68% of patients on valproate vs 52% on placebo; P=0.06).

Side effects were generally rated as mild. These data suggest that anticonvulsants might, be a helpful strategy in the treatment of agitation and aggression in dementia. Inhibitors,research,lifescience,medical However, further placebo-controlled trials are required to explore the clinical efficacy and tolerability of these compounds, particularly of the new generation of anticonvulsants. Because aggressive patients do not always respond to medication (single drug or in combination), one-to-one nursing in a quiet room is sometimes Alvocidib datasheet indicated.

Sleep disturbances Sleep disturbances in AD patients are characterized by fragmented sleep or disruption in the day–night sleep Inhibitors,research,lifescience,medical cycle.8 They appear to become progressively worse as the disease progresses, although

the severity of this disturbance varies considerably among individual patients. Apart from the neurodegenerative disease process itself, various other factors Inhibitors,research,lifescience,medical may influence the quality of sleep including physical or environmental conditions and drug side effects. Pharmacological conditions and drug side effects. Pharmacologically, chloralhydrate Inhibitors,research,lifescience,medical (250–1000 mg/24 hours), new nonbenzodiazepine hypnotics, such as Zolpidem (5–10 mg at night), an imidazopyridine derivative, zopiclonc (3.75–7.5 mg at night), a cyclopyrrolone-dcrivative, and low-potency neuroleptics (eg,melperone 25–75 mg at night) have been found effective.20 Trazodone, a sedative antidepressant agent with anxiolytic properties and minor anticholinergic effects improves sleep disorders (25–75 mg). However, some patients may develop hypotension. Anxiety Anxiety occurs in 50% to 80% of patients with AD.7,9,13 However, in contrast to agitation, aggression, psychosis, and depression, anxiety has been less well studied in patients with Thiamine-diphosphate kinase dementia. Anxiety and depression coexist and overlap with various symptoms, such as agitation and the awareness of the cognitive deficiencies with resulting helplessness. The etiology and pathophysiology of anxiety in AD is not well understood. There is evidence that, anxiety is associated with loss of serotonergic neurons in AD. Antidepressants enhancing serotonergic activity, particularly SSRIs, may improve depression and anxiety.

As with transcriptomics and proteomics, the analytical tools employed in metabolomics can yield massive data sets. The main obstacle in metabolomics studies is that the discovery phase is most commonly undertaken by mass spectrometry (MS) [5,6,7,8,9] or nuclear magnetic resonance (NMR) spectrometry [10,11]. MS and NMR are among the most important

emerging technologies in metabolomics, offering the shortest route toward metabolite identification and quantification [12]. NMR has demonstrated great potential, essentially due to the high measurement reproducibility and the high throughput of analysis [13,14]. However, one major problem in metabolomics studies by NMR is the Inhibitors,research,lifescience,medical relatively poor sensitivity of the technique. Furthermore, the number of MS researchers is much larger than that of NMR researchers trained to acquire metabolomics data [15]. In parallel, capillary electrophoresis (CE) [16], gas chromatography (GC) [17], and high performance Inhibitors,research,lifescience,medical liquid chromatography (HPLC) [18,19,20] separation techniques coupled to online MS detection can provide higher levels of sensitivity. Many important endogenous metabolites exist at very low concentrations in biological systems. Metabolomics could enable mapping of perturbations of early biochemical changes in diseases and hence provide an opportunity Inhibitors,research,lifescience,medical to develop predictive biomarkers that could result

in earlier intervention and provide valuable insights into the mechanisms of diseases. The primary goal of metabolomics analysis is the unbiased relative quantification of every metabolite in a biological Inhibitors,research,lifescience,medical system. Organic acids and amino acids represent metabolite classes of high significance because these metabolites are involved in a multitude of biochemical pathways and fluxes and are thus important for the diagnosis/evaluation of

a number of critical metabolic states. However, these metabolite classes can be difficult to separate from each other and matrix components because of their polar nature. In this review, we introduce various separation methods, such as CE, GC, and HPLC, for the determination Inhibitors,research,lifescience,medical of endogenous highly polar metabolites in biological samples. 2. Non-Target and Target Metabolomics Metabolomics is a promising and approach aimed at facilitating our understanding of the dynamics of the biological composition in living systems. Metabolomics is classified into non-targeted or targeted metabolomics. Non-targeted metabolomics seeks to assign as many compounds as possible by BI 6727 mw either de novo analyte identification or ideally, utilizing reference standards to achieve the highest level of confidence. Changes in the metabolites can be mapped to specific pathways, thereby providing mechanistic information of the process under study. Targeted metabolomics measures analytes that have been selected a priori, on the basis of known biology and chemistry.

4 per 1 000 inhabitants per year of acutely ill patients with chest pain or suspected acute myocardial infarction was found. In a previous study [1] we presented data from three EMCCs after gathering information on every situation that was triaged as a red response, according to the JNK inhibitor clinical trial Norwegian Index of Medical Emergencies. The study showed that 90% of the red responses were medical problems with a large variation of symptoms, the remainder being accidents. Severity of illness was classified retrospectively,

and showed Inhibitors,research,lifescience,medical that 70% of the patients were not in a life-threatening situation. The aim of the present analyses was to obtain representative data on the epidemiology of acute chest pain outside the hospitals in Norway, by a more detailed investigation of the data from our EMCC study. Methods Three EMCCs, located at Haugesund, Stavanger and Innlandet hospitals, were involved in the study, with the three Inhibitors,research,lifescience,medical corresponding districts covering 816 000 inhabitants (18% of the total Norwegian population). Data were collected Inhibitors,research,lifescience,medical prospectively from October 1 to December 31 2007. Variables All 19 EMCCs in Norway use a software system called Acute Medical Information System (AMIS) to record all incoming cases. Usage of the AMIS results in an electronic form with registration of each incident

(not the individual patient). The AMIS form contains information about the incident, the patient (or patients, if more than one patient is involved in the incident) and all available logistics, including date, time of day, and to where the patients are transported (“left at scene”, home, casualty clinic,

hospital). Prehospital response time is also registered, Inhibitors,research,lifescience,medical defined as the time period from when the caller calls 113 until the nearest available ambulance reaches the patient [9,10]. Based on the immediate available information, the EMCC operator (usually a specially trained Inhibitors,research,lifescience,medical nurse) gives the incident one clinical criteria code and one response level according to the Index [6]. The Index is based on ideas from the Criteria Based Dispatch system in the US [11], and was first published in 1994. It categorises clinical PD184352 (CI-1040) symptoms, findings and incidents into 39 chapters, and each chapter is subdivided into a red, yellow and green criteria based section, correlating to the appropriate level of response. Red colour is defined as an “acute” response, with the highest priority, and will trigger the transmission of a radio alarm to both the primary care doctor on-call and the ambulance service. Yellow colour is defined as an “urgent” response, with a high, but lower priority, where the patient should be examined as soon as the doctor-on-call is available. Green colour is defined as a “non-urgent” response, with the lowest priority. Chapter 10 in the Index covers the symptom “Chest pain”, and usage of the red response section will result in the code A10 – Chest pain (A for “acute”).

subtilis (data of both organisms were taken from [5]), S. cerevisiae [30], Hansenula polymorpha and two Pseudomonas strains. On average, the metabolic flux ratio analysis with Flux-P runs about three to five times faster than the manual analysis.

The same holds for the calculation of the flux distribution in netFlux. Hence, a complete 13C-based MFA (including file upload to the BKM120 price server) performed with Flux-P requires about 4 min instead of 12 to 20 min needed for a manual analysis. As metabolic flux experiments do not only produce a single data set that has to be analyzed, but often 20, 50 or even 150 data sets, this means that the time spent for the data analyses for Inhibitors,research,lifescience,medical an experiment is now only about 1:20 h, 3:20 h,

or 10 h instead of up to 6:40 h, 16:40 h, or 50 h, respectively. Furthermore the manual analysis requires the full attention of an (experienced) Inhibitors,research,lifescience,medical human user, hence it is expensive in the sense that it can easily consume a whole man-week of work. In contrast, the automatic analysis workflows run autonomously in the background, possibly overnight, so that the researcher can focus on other tasks in the meantime. For analysis Inhibitors,research,lifescience,medical procedures that do not involve human interaction, it is easy to see that the automation of the in silico experiment using workflow technology increases the speed of the analyses without influencing the results at all. However, workflow realizations of usually interactive analysis processes do not necessarily impact the quality of the results: it is often possible Inhibitors,research,lifescience,medical to identify quantifiable criteria in the human expert’s analysis behavior, and apply these for at least heuristic user interaction emulation. The quality of the calculated metabolic flux ratios and intracellular fluxes was investigated Inhibitors,research,lifescience,medical by a systematic comparison with the results of the manual analysis. In general, calculated ratios and reaction rates, automatically and manually calculated, coincided quite well. As an example a comparison of automatically and

manually calculated flux distributions and metabolic flux ratios are shown in Figure 5 and Figure 6. For the estimation of the E. coli and B. subtilis flux distributions, data from 1-13C and U-13C-labeling experiments were available Olopatadine and combined for the analysis (using the workflow shown in Figure 4A). These comprehensive datasets resulted in flux distributions with very high congruency (linear correlation coefficients above 0.99). Moreover, we checked if the data analysis workflow is consistent by repeating the analysis of several datasets 20 times. In all calculations both metabolic flux ratios and fluxes were almost identical with only minor differences in the metabolic flux ratios that did not impact the net flux distribution. Figure 6 Consistency of metabolic flux ratio analysis calculated with Flux-P. H. polymorpha metabolic flux ratios (unpublished data) calculated manually with FiatFlux and with Flux-P show high congruency.

Pharmacoeconomic studies are health economic studies used increasingly by insurance companies, governments, and other providers of health services to decide whether to adopt a new drug. Because the efficacy of anti-AD drugs is not very great, the

issue of cost effectiveness was raised as soon as these drugs were approved for marketing. For example, in a study of donepezil’s effect on health care cost and utilization, potential savings derived from decrease in medical cost were found to be neutralized by increase in the direct cost due to the high cost of medication.12 Nevertheless, there is a trend indicating that these Inhibitors,research,lifescience,medical treatments have the potential to offer cost savings,12-14 but these trends are mostly expressed as economic models rather than real-life studies. For example, in some studies,13,15 tacrine reduced the cost of caring for an AD patient by reducing cost of both institutionalization and home care. Finally, in a recent. Canadian study, it was found that

rivastigmine delayed the transition to more severe stages of AD. As severity of Inhibitors,research,lifescience,medical illness is related to higher costs, the consequence of this delay is cost savings.16 The main limitation of pharmacoeconomic studies is that they are very rarely designed a priori to address pharmacoeconomic questions. Most often, they arc pivotal Inhibitors,research,lifescience,medical phase 3 drug trials, to which secondary measurements addressing pharmacoeconomics are added. Hence, they suffer from Inhibitors,research,lifescience,medical all the limitations of controlled trials (selected patient populations, restricted outcome measurements and laboratory instead of real life clinical care). Whose costs

are we measuring? In the final analysis, whether a treatment, intervention, or service is cost-effective depends very much on who is paying for it.17 Too often, “novel, innovative” interventions and services result in cost shifting rather than saving resources or providing better care. For example, this website depending on the organization of health care and the insurance status of the patient, the transfer of a patient from home to institutionalization may decrease the family out-of-pocket expenses and increase the insurer expenses, who now has to cover Inhibitors,research,lifescience,medical the cost of institutionalization. Similarly, a drug that delays institutionalization might increase (-)-p-Bromotetramisole Oxalate the expenses of the local authorities, which are often covering the cost of day-care centers, and decrease the cost of the private or governmental insurance agency that covers the cost of a nursing home. Finally, indirect cost related to the care provided for free by a healthy spouse or child has monetary meaning only if the caregiver can obtain gainful employment instead of being a caregiver. This is particularly relevant in AD where most of the caregivers are spouses who are often, but not always, retired. In this case, quality of life rather than cost is the relevant variable, but pricing the quality of life of a demented individual or even of an elderly caregiver is a daunting task.

Many critical analyses have been published, eg, the recently published article by Tucker.10 The

current DSM and ICD process gives the image of precision and exactness. Indeed, we as psychiatrists have come to believe that we are dealing with clear and discrete disorders rather than arbitrary symptom clusters. We are now being taken at our own word by managed care companies that stipulate that if a patient’s symptoms fulfill current criteria for schizophrenia or recurrent depressive disorder, drug treatment must be given strictly according to the textbook. In fact, to quote Gary J. Tucker “at best, we are between Scylla and Inhibitors,research,lifescience,medical Charybdis – we no longer want to say that each patient is a unique individual, nor can we honestly say that every case clearly fits diagnostic criteria.”10 All of this apparent precision overlooks the fact that, as yet, we have no identified etiological agents for psychiatric disorders. Inhibitors,research,lifescience,medical In psychiatry, no matter how scientifically and precisely we use scales to evaluate the patient’s pathological symptoms, all Inhibitors,research,lifescience,medical we are really doing is simply pattern recognition. We are still only making

an empirical diagnoses and not etiological ones based on disruptions of structure of function. After these considerations I would like to briefly consider some more optimistic perspectives that I believe could positively influence psychiatric classification and nosology in the near future. New, exciting concepts and paradigms are looming on the horizon of psychiatric classification. New intellectual frameworks for psychiatry have been introduced, for example by Kandel,11 who proposes that the genes expressed Inhibitors,research,lifescience,medical in the

brain encode proteins that play important roles at specific stages of the development, maintenance, and regulation of the neural circuits that underlie behavior. Modern cognitive Doramapimod datasheet psychology is exploring language, perception, memory, motivation, and skilled movements in ways that are proving Inhibitors,research,lifescience,medical to be stimulating, insightful, and rigorous. The recent merger of cognitive psychology with neural science, to give birth to cognitive neuroscience, is proving to be one of the most exciting areas in biology. Through these and others hypotheses, psychiatry is searching for a new identity and a new Thiamine-diphosphate kinase nosological approach. ICD-10 and DSM-IV have offered psychiatrists worldwide consensual and more or less valid diagnostic hypotheses. But now, after years of extensive use, the time has come for a critical appraisal of both classifications. A renewed involvement of psychiatry with biology and neurology is not only scientifically important, but also epitomizes the scientific competence that should be the basis for the clinical specialty of psychiatry in the near future.

Two other ports were also placed, a 10-mm port 2 fingers below the right subcostal margin at a level between the xiphoid and the umbilicus, and a 5-mm port midway between the umbilicus and the anterior-superior iliac spine. As the patient had a large abdomen, all ports were inserted 2 to 3 fingers lateral to previously inserted port sites. The insufflation pressure was kept at 10 mm Hg. Standard laparoscopic nephrectomy was successfully completed. The specimen was removed by lateral enlargement of the lower port incision and the patient remained

stable throughout the procedure, which was 188 minutes in duration including the anesthesia time. Fetal cardiac activity was monitored throughout the procedure and Inhibitors,research,lifescience,medical patient and fetal stability were ascertained at Inhibitors,research,lifescience,medical the end of the procedure. Postoperatively, she was given a maintenance dose of isoxsuprine for 3 days and fetal cardiac activity was monitored at regular intervals. She was discharged on the fifth postoperative day (Figure 1). The remainder of the pregnancy was uncomplicated. She had a normal vaginal delivery at term, giving birth to a healthy female child weighing 2850 g. Figure 1 Photograph of the patient on the fifth postoperative day. Scars of previous surgery (right laparoscopic ureterolithotomy) can also be seen. Discussion When pyonephrosis complicates pregnancy, maternal ill health makes management

difficult, Inhibitors,research,lifescience,medical and necessitates careful consideration of risks of both the disease Inhibitors,research,lifescience,medical and the intervention to http://www.selleckchem.com/erk.html mother and fetus. Cystoscopy and retrograde stent insertion can be performed under local anesthesia, but are associated with a small miscarriage rate.2 USG-guided PCN can be safely performed during pregnancy to maintain the drainage

of pyonephrosis until delivery3; it may not be effective in all cases.4 Dovlatian and colleagues4 reviewed the records of 120 pregnant Inhibitors,research,lifescience,medical women with pyodestructive forms of pyelonephritis. Eighty-three women underwent PCN that was ineffective in 12 patients (14.5%) who ultimately required nephrectomy,4 which is the best option in total destruction of the kidneys.3 Furthermore, when inserted during early pregnancy, PCN has increased chances of either falling first out or becoming calcareous, which will necessitate multiple repeat nephrostomies throughout the pregnancy2 as in our case, thus increasing morbidity. Our patient was initially managed with prolonged PCN but it was not effective and got blocked very frequently, leading to morbidity and sepsis. The decision to operate on the patient and remove the kidney was difficult and was based on consideration of wishes and concerns of the mother and her family members, as well as the advantages and disadvantages of laparoscopic nephrectomy at this stage. Until recently, abdominal emergencies have been managed by open procedures. With increasing experience as well as technical advances in laparoscopic surgery, many surgeries are being performed in a minimally invasive fashion,5 even in pregnant patients.

As an important study limitation we have to say that we only compared two groups in the present study: an experimental group and a control group. Given a large placebo response in several samples, it could be that our results are only the consequences of a placebo effect. Thus, future studies should also add a placebo group to the experimental design. To compare the effectiveness of the wingwave method to CBT for example, researchers could further add another group which gets an intervention with the CBT. A comparison of EMDR and CBT in the treatment of PD was Inhibitors,research,lifescience,medical already done by Faretta (2012) and the results showed that both treatments Inhibitors,research,lifescience,medical are effective

for the resolution of a PD. However, EMDR treatment seems to have a faster progress in symptom reduction which is maintained over time. Another comparison could be conducted between EMDR and wingwave in the treatment of anxiety and analyses can potentially show if the wingwave method is

an improved alternative to EMDR. Sirtuin inhibitor Furthermore, future research could Inhibitors,research,lifescience,medical check, if there are time-dependent effects of the method. In the present study, participants received an intervention with the wingwave method 2 weeks after the first time of measurement and another 2 weeks later, participants completed the second time of measurement. Thus, it may be interesting to find out how stable the present results are over a longer period of time. To the best of our knowledge, the present study was the first one to investigate the effects of the wingwave method in reducing anxiety. The results from this pilot study seem promising Inhibitors,research,lifescience,medical to help people in the future to decrease rapidly their anxiety. We hope that this study will help to inform and motivate future research to further investigate this new method in the treatment

of anxiety. Conflict of Interest None declared.
The Inhibitors,research,lifescience,medical earliest studies of the corpus callosum (cc), the largest neural pathway connecting the two cerebral only hemisperes (Innocenti 1986), date back to 16th century. Considered for many centuries as the “seat of the soul” (Manzoni 1998), it took until the 18th century for Franz Joseph Gall and Johann Spurzheim to dissect alcohol-fixed brains and describe bundles of axons passing through the white matter and connecting the two hemispheres (Manzoni 2011). The cc is made up of myelinated and unmyelinated axons and glial cells (Innocenti 1986). Callosal axons originate from pyramidal neurons located in layers II/III and V of the cerebral cortex (Innocenti 1986) and use glutamate as neurotransmitter (Barbaresi et al. 1987), released in the cc by unmyelinated fibers at specific axon–glia synaptic junctions (Ziskin et al. 2007).

The greater frontal activation in inconsistent patients compared with consistent SZ may appear surprising, given that this region is often associated with higher cognitive functions and yet these patients showed poorer performance on the DD task. However, abnormal prefrontal cortex activation is one of the most replicated findings in SZ, with Inhibitors,research,lifescience,medical reports of hyper- and hypoactivation associated with fluctuating task difficulty and performance (Glahn et al. 2005). More activation in our inconsistent patients than consistent patients during the DD task may reflect inefficient processing

during task performance. Study limitations For the main fMRI contrasts done in this study we opted to match patients and HC based on performance which led us to exclude about a third of our patient Inhibitors,research,lifescience,medical population. This significantly limits the generalization of the results. The behavioral results from the inconsistent patients suggest that the task was too difficult and/or that the participants were not meaningfully engaged in the task. Inhibitors,research,lifescience,medical In future

imaging studies, these patients could be compared with HC using a parametric equivalent of the DD task. All SZ in this study were on stable doses of antipsychotic GSK2656157 medications, which may influence the BOLD fMRI signal (Roder et al. 2010). In addition, there was a trend level difference between the number of smokers Inhibitors,research,lifescience,medical in the consistent SZ group and the consistent HC group, and smoking negatively impacts the brain (Durazzo et al. 2006; Gallinat et al. 2007). However, two recent studies that took smoking into consideration found no group differences in DD between SZ and HC (MacKillop and Tidey 2011;

Wing et al. 2012; but see Ahn et al. 2011). Performance on the RBANS was significantly impaired in consistent and inconsistent SZ compared with consistent HC. These cognitive deficits could contribute to differences in activation across a wide variety of tasks, including the Inhibitors,research,lifescience,medical present DD task. DD may also be influenced by a person’s financial status. Given the financial circumstances of patients with chronic illness, this may be a psychological factor influencing behavior unrelated to symptoms associated with SZ. Finally, our small sample sizes did not allow us to pursue meaningful correlations with relevant factors, such Farnesyltransferase as cognitive and clinical measures. Conclusions Our results point to disruption of several neural networks during decision making, including executive, reward, default mode, and emotional, and suggest processes that are disturbed during decision making in SZ. In the face of matched behavior, executive and reward networks were less activated, while regions of the DMN that are usually deactivated during a task were more activated.

044 and 0.460 respectively, paired t-test, Figure 4). Interestingly,

TGFB1 BGJ398 ic50 expression showed step-wise increase from polyp, to normal, to tumour (P=0.016, ANOVA). Further analysis (Post-Hoc Tukey test) pointed out significant differences in expression between tumours and polyps (P=0.029), but not between tumours and TAN (P=0.345) and between polyps and TAN (P=0.914) (Figure 4). Figure 4 TGFB1 and its receptors expression in CRC tumour & normal tsssue The relationship between TGFB1, TGFBR1 and TGFBR2 was further investigated using Pearson correlation. Inhibitors,research,lifescience,medical No violation of the assumption of normality, linearity and homogenecity was ensured before conducting further analysis. There was positive correlation between all the variables in both tumour and TAN colorectal tissues with high expression level of the ligand Inhibitors,research,lifescience,medical associated with high expression of the receptors (Table 3). The relation of TGFB1 and its receptors expression levels and the clinico-pathological parameters were examined using ANOVA and t-test (Figure 4). Although high level of TGFB1 was documented in tumours compared to normal colorectal tissues, we noticed an association of TGFB1 down-regulation and lymphovascular invasion (P=0.035). Both TGFBR1 and TGFBR2 were under-expressed in proximal colon, however, the difference was only significant for TGFBR2 (P=0.003). TGFBR1 showed reduced expression Inhibitors,research,lifescience,medical in association with advanced disease clinicopathological

parameters like tumour size, poor differentiation, advanced nodal stage, advanced Dukes’ stage and tumour invasion and metastasis

Inhibitors,research,lifescience,medical (Table 3), However, these associations were only significant in relation to bowel wall involvement (P<0.001), and raised CEA serum level (P=0.045). Down-regulation of TGFBR2 was significantly associated with increased bowel wall involvement (P=0.006), in colon cancer compared to rectal cancer (P=0.031) and in association with perineural (P=0.030) and lymphovascular Inhibitors,research,lifescience,medical invasion (P=0.012). No significant differences were identified in CEACAM5 expression levels in tumour compared to TAN colorectal tissues (P=0.981, t-test). In addition, no enough significant correlations were found between CEACAM5 expression and the CEA serum level (r=-134, n=79, P=0.240). Higher expression of CEACAM 5 was associated with moderately differentiated tumours (P=0.016) and local (P=0.002) and lymphovascular invasion (P=0.019) (Kruskal-Wallis and Mann-Whitney tests, Table 3). Neoadjuvant therapy and colorectal cancer genes expression In the cohort of rectal cancer patients (n=58) we analysed the differences in gene expression in patients who had neoadjuvant chemoradiation (n=25) compared to those who did not (n=33) using t-test. Univariate analysis of variance was further conducted to test for interaction effect and to control for confounding factors. We demonstrated decrease expression of CDH17 (P=0.020) and CEACAM5 (P=0.032) and increase expression of CXCL12 (P<0.001), CXCR4 (P=0.004) and MUC2 (P=0.