Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance

<p>Abstract</p> <p>Background</p> <p>Organic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>OCT1 (<it>SLC22A1</it>) and OCT3 (<it>SLC22A3</it>) mRNA expression was measured in primary human HCC and corresponding non neoplastic tumor surrounding tissue (TST) by real time PCR (n = 53). Protein expression was determined by western blot analysis and immunofluorescence. Data were correlated with the clinicopathological parameters of HCCs.</p> <p>Results</p> <p>Real time PCR showed a downregulation of <it>SLC22A1 </it>and <it>SLC22A3 </it>in HCC compared to TST (p ≤ 0.001). A low <it>SLC22A1 </it>expression was associated with a worse patient survival (p < 0.05). Downregulation was significantly associated with advanced HCC stages, indicated by a higher number of T3 tumors (p = 0.025) with a larger tumor diameter (p = 0.035), a worse differentiation (p = 0.001) and higher AFP-levels (p = 0.019). In accordance, <it>SLC22A1 </it>was less frequently downregulated in tumors with lower stages who underwent transarterial chemoembolization (p < 0.001) and liver transplantation (p = 0.001). Tumors with a low <it>SLC22A1 </it>expression (< median) showed a higher <it>SLC22A3 </it>expression compared to HCC with high <it>SLC22A1 </it>expression (p < 0.001). However, there was no significant difference in tumor characteristics according to the level of the <it>SLC22A3 </it>expression.</p> <p>In the western blot analysis we found a different protein expression pattern in tumor samples with a more diffuse staining in the immunofluorescence suggesting that especially OCT1 is not functional in advanced HCC.</p> <p>Conclusion</p> <p>The downregulation of OCT1 is associated with tumor progression and a worse patient survival.</p

Perceiving What Is Reachable Depends on Motor Representations: Evidence from a Transcranial Magnetic Stimulation Study

Background: Visually determining what is reachable in peripersonal space requires information about the egocentric location of objects but also information about the possibilities of action with the body, which are context dependent. The aim of the present study was to test the role of motor representations in the visual perception of peripersonal space. Methodology: Seven healthy participants underwent a TMS study while performing a right-left decision (control) task or perceptually judging whether a visual target was reachable or not with their right hand. An actual grasping movement task was also included. Single pulse TMS was delivered 80 % of the trials on the left motor and premotor cortex and on a control site (the temporo-occipital area), at 90 % of the resting motor threshold and at different SOA conditions (50ms, 100ms, 200ms or 300ms). Principal Findings: Results showed a facilitation effect of the TMS on reaction times in all tasks, whatever the site stimulated and until 200ms after stimulus presentation. However, the facilitation effect was on average 34ms lower when stimulating the motor cortex in the perceptual judgement task, especially for stimuli located at the boundary of peripersonal space. Conclusion: This study provides the first evidence that brain motor area participate in the visual determination of what is reachable. We discuss how motor representations may feed the perceptual system with information about possibl

Muscles in “Concert”: Study of Primary Motor Cortex Upper Limb Functional Topography

BACKGROUND: Previous studies with Transcranial Magnetic Stimulation (TMS) have focused on the cortical representation of limited group of muscles. No attempts have been carried out so far to get simultaneous recordings from hand, forearm and arm with TMS in order to disentangle a 'functional' map providing information on the rules orchestrating muscle coupling and overlap. The aim of the present study is to disentangle functional associations between 12 upper limb muscles using two measures: cortical overlapping and cortical covariation of each pair of muscles. Interhemispheric differences and the influence of posture were evaluated as well. METHODOLOGY/PRINCIPAL FINDINGS: TMS mapping studies of 12 muscles belonging to hand, forearm and arm were performed. Findings demonstrate significant differences between the 66 pairs of muscles in terms of cortical overlapping: extremely high for hand-forearm muscles and very low for arm vs hand/forearm muscles. When right and left hemispheres were compared, overlapping between all possible pairs of muscles in the left hemisphere (62.5%) was significantly higher than in the right one (53.5% ). The arm/hand posture influenced both measures of cortical association, the effect of Position being significant [p = .021] on overlapping, resulting in 59.5% with prone vs 53.2% with supine hand, but only for pairs of muscles belonging to hand and forearm, while no changes occurred in the overlapping of proximal muscles with those of more distal districts. CONCLUSIONS/SIGNIFICANCE: Larger overlapping in the left hemisphere could be related to its lifetime higher training of all twelve muscles studied with respect to the right hemisphere, resulting in larger intra-cortical connectivity within primary motor cortex. Altogether, findings with prone hand might be ascribed to mechanisms facilitating coupling of muscles for object grasping and lifting -with more proximal involvement for joint stabilization- compared to supine hand facilitating actions like catching. TMS multiple-muscle mapping studies permit a better understanding of motor control and 'plastic' reorganization of motor system

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P &lt; 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P &lt; 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

IMPACT OF LACTATION STAGE AND MILK PRODUCTION ON MILK FAT FATTY ACIDS RATIO Animal Production research centre nitra, slovak republic

ABSTRACT Milk fat is, from a nutritional point of view, of the negative value because of the prevalent content of saturated fatty acids with high atherogenic index. intake of milk fat in the diet is important because of the content of monounsaturated fatty acids, acting favorably against cardiovascular diseases and especially of essential fatty acids: linoleic, alpha-linolenic and conjugated linoleic acid (clA), which is found only in meat and milk of ruminants. the analysis of relations of fatty acids in milk fat to qualitative-production parameters of milk shows that the correlations of fatty acids with lactation stage and qualitative-production parameters of milk are quite weak in dairy cows with stable type of nutrition in form of whole-the-year feeding mixed feed ration in lowland agricultural area. Coefficients r&gt;0.3 for the values of lactation sum were observed at monounsaturated fatty acids (MUFAsc), r = 0.467 for days, 0.307 for milk, 0.353 for fat, and 0.340 for protein total production. the most important fatty acids, as far as their content is concerned, c12:0, c14:0, c16:0, c18:0, c18:1n9, the ratio of which is higher than 5 % in milk fat and they represent together about 75 % of milk fat, show no significant relations either to sum or to daily production parameters or to the content of basic components in milk. With the exception of c16:0, palmitic acid (30.93 ± 4.81 % in milk fat), which has negative relation to daily milk (r = -0.404) and protein (r = -0.345) production. this acid has positive relation to the content of fat in milk (r = 0.444) and negative relation to the content of lactose in milk (r = -0.311). clA showed negative correlation with daily fat production (r = -0.407) and content of fat in milk (r = -0.269) and F/P index (r = -0.420)

The raw milk quality from organic and conventional agriculture. Acta univ. agric. et silvic

Abstract ČUBOŇ, J., FOLTYS, V., HAŠČÍK, P., UBREŽIOVÁ, I., KRÁČMAR, S.: The raw milk quality from organic and conventional agriculture. Acta univ. agric. et silvic. Mendel. Brun., 2008, LVI, No. 5, pp. 25-3

Metabolic and electrophysiological validation of functional MRI

OBJECTIVES—Although functional MRI is widely used for preoperative planning and intraoperative neuronavigation, its accuracy to depict the site of neuronal activity is not exactly known. Experience with methods that may validate fMRI data and the results obtained when coregistering fMRI with different preoperative and intraoperative mapping modalities including metabolically based (18)F-fluorodeoxyglucose PET, electrophysiologcally based transcranial magnetic stimulation (TMS), and direct electrical cortical stimulation (DECS) are described.
METHODS—Fifty patients were included. PET was performed in 30, TMS in 10, and DECS in 41 patients. After coregistration using a frameless stereotactic system, results were grouped into overlapping (<1 cm distance), neighbouring (<2 cm), or contradictory (>2 cm).
RESULTS—Comparing fMRI with PET, 18 overlapping, seven neighbouring, and one contradictory result were obtained. In four patients no comparison was possible (because of motion artefacts, low signal to noise ratio, and unusual high tumour metabolism in PET). The comparison of TMS and fMRI showed seven overlapping and three neighbouring results. In three patients no DECS results could be obtained. Of the remaining 38 patients, fMRI hand motor tasks were compared with DECS results of the upper limb muscles in 36patients, and fMRI foot motor tasks were compared with DECS results of the lower limb on 13 occasions. Of those 49 studies, overlapping results were obtained in 31 patients, and neighbouring in 14.On four occasions fMRI did not show functional information (because of motion artefacts and low signal to noise).
CONCLUSIONS—All validation techniques have intrinsic limitations that restrict their spatial resolution. However, of 50 investigated patients, there was only one in whom results contradictory to fMRI were obtained. Although it is not thought that fMRI can replace the intraoperatively updated functional information (DECS), it is concluded that fMRI is an important adjunct in the preoperative assessment of patients with tumours in the vicinity of the central region.