Interval gastric cancer: A call to attentiveness and action.

INTRODUCTION AND AIMS: Endoscopy is the most effective method for identifying gastric adenocarcinoma (GAC). Interval gastric cancer (IGC) is GAC that is diagnosed 2-3 years after a normal endoscopy. Its characteristics are unknown in the Colombian environment. The clinical, histopathologic, and endoscopic characteristics were evaluated, along with the presentation rate, proton pump inhibitor (PPI) use, and IGC survival rate, and compared with other types of GAC. METHODS: A retrospective, analytic study was conducted on a prospective cohort. It evaluated 513 patients with GAC treated at our institution, within the time frame of January 2012 and June 2018. The patients had endoscopic diagnosis of GAC and endoscopy within the past three years that was negative for tumor. RESULTS: A total of 513 patients diagnosed with GAC were evaluated. Forty-two of the patients had IGC (8.2%): 9 early lesions and 33 advanced lesions (79%). The IGCs were smaller (31 vs. 41 mm; P < .01), as well as flatter and more depressed (P < .01). There was no association with PPI use, but there was an association with a history of gastrectomy and anastomosis (P = .02), as well as the absence of red flags (P < .003). The most frequent locations were the gastric body (52%) and the antrum (26%). Overall two-year survival was similar between IGC and GAC (37.1 vs. 39.3%, P = .72). CONCLUSION: A total of 8.2% of recently diagnosed GAC were cases of IGC. The presence of anastomosis and the absence of red flags were related to IGC. Overall survival was poor and there were no differences from the other types of GAC detected.

Impact of intraoperative colonoscopy on anastomotic leakage detection and prevention in colorectal anastomosis for rectal cancer.

INTRODUCTION AND AIM: The value of leakage testing during colorectal resections to identify anastomotic leaks or bleeding has not been established. Our aim was to compare the impact of intraoperative colonoscopy (IOC) versus insufflation with a syringe, as leakage testing in lower anterior resection (LAR) for rectal cancer, with respect to the incidence of postoperative leakage (PL). MATERIALS AND METHODS: A retrospective study utilizing a prospective database of 426 patients with rectal cancer that underwent elective LAR, within the time frame of January 2015 and December 2019, was conducted. The anastomotic leak test was chosen by the surgeon. The incidence of postoperative leakage was compared between patients that underwent IOC and those that had the syringe leak test, utilizing the logistic regression analysis. Propensity score matching was included. RESULTS: There were no significant differences in the clinical characteristics or morbidity and mortality rates between the two groups. Four patients were excluded, leaving a patient total of 422. Seventy patients with IOC were compared with 352 that had the syringe leak test. The incidence of postoperative leakage was 5.7% in the IOC group and 12.2% in the control group (p = 0.001). After propensity score matching (n = 221), balancing the characteristics between the groups, the incidence of postoperative leakage was 5.7% in the IOC group and 13.9% in the syringe leak test group (p = 0.001). CONCLUSION: IOC was shown to be a safe method for evaluating the integrity of colorectal anastomosis and was associated with a higher percentage of protective stoma use, appearing to reduce the risk for PL.

Comparative Analysis of the Biosimilar and Innovative G-CSF Modulated Pathways on Umbilical Cord Blood-Derived Mononuclear Cells.

Biosimilars of granulocyte colony-stimulating factor (G-CSF) have been routinely introduced into clinical practice. However, not functional genomics characterization has been performed yet in comparison with the innovator G-CSF. This study aimed to evaluate the transcriptomic changes in an in vitro model of umbilical cord blood cells (UBC) exposed to G-CSF for the identification of their modulated pathways. Umbilical cord blood cells-derived mononuclear cells (MNCs) were treated with biosimilar and innovator G-CSF for further gene expression profiling analysis using a microarray-based platform. Comparative analysis of biosimilar and innovator G-CSF gene expression signatures allowed us to identify the most commonly modulated pathways by both drugs. In brief, we observed predominantly upmodulation of transcripts related to PI3K-Akt, NF-kappaB, and tumor necrosis factor (TNF) signaling pathways as well as transcripts related to negative regulation of apoptotic process among others. In addition, hematopoietic colony-forming cell assays corroborate the G-CSF phenotypic effects over UBC-derived MNCs. In conclusion, our study suggests that G-CSF impacts UBC-derived cells through the modulation of several signaling pathways associated with cell survival, migration, and proliferation. The concordance observed between biosimilar and innovator G-CSF emphasizes their similarity in regards to their specificity and biological responses.

Human papilloma virus genotypes in dysplasia and epithelial hyperplasia of oral cavity using the luminex xmap technology. A multicenter study.

BACKGROUND: Oral cancer associated with high risk (HPV-HR) human papilloma virus (HPV) has been increasing. HPV-HR has been associated with epithelial dysplasia, however, little information exists on its frequency in epithelial hyperplasia lesions. The aim of this study is to compare HPV genotypes in dysplastic and hyperplastic lesions of oral cavity. MATERIAL AND METHODS: Two hundred and fifty oral lesions: 131 dysplasia and 119 hyperplasia from two regions of Colombia were evaluated. One hundred seventy-four coming from urban area and 104 from a high risk population to oral cancer from a rural area. HPV was identified by qPCR and Twenty-four HPVs genotypes were evaluated by Luminex® technology. Logistic regressions were performed to establish the associations between HPV infections with oral dysplasia. RESULTS: Twenty-eight percent (70/250) of the samples were positives for any HPV and HPV-HRs were more frequently than low risk HPVs. HPV-16 was the most detected genotype (16%) followed by HPV-31, 53, 18 and 45. HPV, HPV-HRs and HPV-16 were only associated with dysplasia in urban area; OR 3.28 (CI 95% 1.49-7.17), OR 7.94 (CI 95% 2.97-21.2) and OR 5.90 (CI 95% 2.05-17). Individuals in rural area showed more HPV and HPV-HRs infection in hyperplasic lesions than urban population. The majority of HPV+ lesions had multi-type of HPV (52/70) and the urban individuals showed more genotypes than rural population. CONCLUSIONS: HPV-.HRs are frequently found in hyperplastic and dysplastic epithelial lesions. HPV-HRs and HPV-16 were associated with dysplasia in urban population. Rural high risk population and urban population differ in the frequency and variety of HPV genotypes.

Pharmacokinetics and antinociceptive effects of the soluble epoxide hydrolase inhibitor t-TUCB in horses with experimentally induced radiocarpal synovitis.

This study determined the pharmacokinetics, antinociceptive, and anti-inflammatory effects of the soluble epoxide hydrolase (sEH) inhibitor t-TUCB (trans-4-{4-[3-(4-Trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid) in horses with lipopolysaccharide (LPS)-induced radiocarpal synovitis. A total of seven adult healthy mares (n = 4-6/treatment) were administered 3 µg LPS into one radiocarpal joint and t-TUCB intravenously (i.v.) at 0 (control), 0.03, 0.1, 0.3, and 1 mg/kg in a blinded, randomized, crossover design with at least 3 weeks washout between. Two investigators independently assigned pain scores (at rest, walk and trot) and lameness scores before and up to 48 hr after t-TUCB/LPS. Responses to touching the joint skin to assess tactile allodynia, plasma, and synovial fluid (SF) t-TUCB concentrations were determined before and up to 48 hr after t-TUCB/LPS. Blood and SF were collected for clinical laboratory evaluations before and up to 48 hr after t-TUCB/LPS. Areas under the curves of pain and lameness scores were calculated and compared between control and treatments. Data were analyzed using repeated measures ANOVA with Dunnett or Bonferroni post-test. p < .05 was considered significant. Data are mean ± SEM. Compared to control, pain, lameness, and tactile allodynia were significantly lower with 1 mg/kg t-TUCB, but not the other doses. For 0.1, 0.3, and 1 mg/kg t-TUCB treatments, plasma terminal half-lives were 13 ± 3, 13 ± 0.5, and 24 ± 5 hr, and clearances were 68 ± 15, 48 ± 5, and 14 ± 1 ml hr-1  kg-1 . The 1 mg/kg t-TUCB reached the SF at high concentrations. There were no important anti-inflammatory effects. In conclusion, sEH inhibition with t-TUCB may provide analgesia in horses with inflammatory joint pain.

Comparison of two tourniquet application times for regional intravenous limb perfusions with amikacin in sedated or anesthetized horses.

Regional limb perfusion (RLP) in horses has proven to be a simple and effective technique for the treatment of synovial and musculoskeletal infections in the distal portion of the limbs. The ideal tourniquet time needed to achieve therapeutic synovial concentrations remains unknown. The pharmacokinetic effects of general anesthesia (GA) versus standing sedation (SS) RLP on synovial amikacin concentrations are not completely understood. This study investigated the pharmacokinetic effects of RLP under general anesthesia (GA) versus standing sedation (SS) on synovial amikacin concentration following 20 or 30 min tourniquet time. Using 1 g of amikacin RLP was performed in two groups of six horses (GA and SS). A pneumatic tourniquet was applied proximal to the carpus and maintained for 20 or 30 min. Two weeks later, the opposite treatment (20 or 30 min) was randomly performed in the opposite limb of horses in each group (GA and SS). Synovial fluid samples were collected from the metacarpophalangeal (MCP) and radiocarpal (RC) joints. Amikacin was quantified by a fluorescence polarization immunoassay. Regardless of the group, no significant difference in the synovial amikacin concentrations was noted between 20 and 30 min RLP. Mean synovial concentrations of amikacin in the standing sedated horses were significantly higher in the MCP joint at 30 min (P = 0.003) compared to horses under general anesthesia. No significant difference was noted for the RC joint.

Effect of emptying the vasculature before performing regional limb perfusion with amikacin in horses.

REASONS FOR PERFORMING STUDY: Emptying the vasculature with an Esmarch bandage before i.v. regional anaesthesia is commonly performed in human patients to prevent leakage of the solution under the tourniquet but there is no evidence for its efficacy in horses for antimicrobial i.v. regional limb perfusion (IV-RLP). OBJECTIVES: To determine the effect on synovial fluid concentration of amikacin of emptying the vasculature before performing IV-RLP. STUDY DESIGN: Crossover experiment. METHODS: Eight clinically healthy horses underwent 2 IV-RLP with amikacin in a randomised, crossover design. Horses received an IV-RLP with amikacin with or without exsanguination before applying a pneumatic tourniquet at the level of the forearm. Blood was collected from the jugular vein (before tourniquet removal) and synovial fluid from the radiocarpal and metacarpophalangeal joints (5 min after tourniquet removal and at 24 h) for amikacin determination. The procedure was video recorded to assess horse movement. RESULTS: There was no difference in amikacin concentrations in the plasma or synovial fluid from the radiocarpal joint between groups. There was a higher concentration of amikacin in the synovial fluid from the metacarpophalangeal joint immediately after tourniquet removal in the group with exsanguination of the limb prior to IV-RLP (mean ± s.d.: no exsanguination 49.7 ± 53.7 µg/ml, exsanguination 257.4 ± 149.7 µg/ml, P = 0.04). Horse movement did not differ significantly between groups. CONCLUSIONS: Emptying the vasculature with an Esmarch bandage before IV-RLP can improve amikacin concentrations in the metacarpophalangeal joint of horses with no effect on the levels of amikacin in the radiocarpal joint.

The effect of a hay grid feeder on feed consumption and measurement of the gastric pH using an intragastric electrode device in horses: a preliminary report.

REASONS FOR PERFORMING STUDY: Obesity and gastric ulceration are highly prevalent in horses. Management modifications for preventing squamous gastric ulceration include frequent feeding and free access to pasture; however, these practices may predispose horses to obesity. OBJECTIVES: To compare the percentage of hay consumed, intragastric pH and horse activity between feeding from the ground and a hay grid feeder. STUDY DESIGN: Crossover experimental study. METHODS: A pH electrode was inserted into the stomach to record the intragastric pH for 48 h. Horses received 1% of their body weight in grass hay twice a day. Horses were assigned to be fed from the ground or a commercial hay grid feeder for 24 h and then switched to the opposite protocol for an additional 24 h. Horses were continuously video-recorded and the percentage of time spent eating or drinking, walking or standing, and lying down were calculated. Two point data were compared by paired t test and pH over time was compared by repeated measures ANOVA. RESULTS: Horses consumed significantly greater amounts of grass hay when fed on the ground compared with a hay grid feeder (n = 9; P<0.001). There were no significant differences between the groups for mean intragastric pH values (n = 6; P = 0.97), mean intragastric pH over time (n = 6; P = 0.45) the length of time the pH was below 4.0 (n = 6; P = 0.54), and the percentage of time horses spent eating or drinking (n = 9; P = 0.52), walking or standing (n = 9; P = 0.3), or lying down (n = 9; P = 0.4). Within each group horses spent more time eating during the day compared with the night (n = 9; hay grid feeder P = 0.003; ground feeding P = 0.007). CONCLUSIONS: The hay grid feeder studied may be used to reduce the amount of hay ingested by horses without reducing the time horses spend eating.

Parametric spectral analysis of nonstationary fluctuations of excitatory synaptic currents.

We assessed on Monte-Carlo simulated excitatory post-synaptic currents the ability of autoregressive (AR)-model fitting to evaluate their fluctuations. AR-model fitting consists of a linear filter describing the process that generates the fluctuations when driven with a white noise. Its fluctuations provide a filtered version of the signal and have a spectral density depending on the properties of the linear filter. When the spectra of the non-stationary fluctuations of excitatory post-synaptic currents were estimated by fitting AR-models to the segments of current fluctuations, assumed to be stationary and independent, the parameter and spectral estimates were scattered. The scatter was much reduced if the time-variant AR-models were fitted using stochastic adaptive estimators (Kalman, recursive least squares and least mean squares). The ability of time-variant AR-models to accurately fit the current fluctuations was monitored by comparing the fluctuations with predicted fluctuations, and by evaluating the model-learning rate. The median frequency of current fluctuations, which could be rapidly tracked and estimated from the individual quantal events (either Monte-Carlo simulated or recorded from pyramidal neurons of rat hippocampus), rose during the rise phase, before declining to a lower steady-state level during the decay phase of quantal event, whereas the variance showed a broad peak. The closing rate of AMPA channels directly affects the steady-state median frequency, whereas the transient peak can be modulated by a variety of factors-number of molecules released, ability of glutamate molecules to re-enter the synaptic cleft, diffusion constant of glutamate in the cleft and opening rate of AMPA channels. In each case, the effect on the amplitude and decay time of mEPSCs and on the current fluctuations differs. Each factor thus leaves its own kinetic fingerprint arguing that the contribution of such factors can be inferred from the combined kinetic properties of individual mEPSCs.

On practical issues about interference in telecare applications based on different wireless technologies.

Telemedicine systems have been progressively paying more and more attention to wireless technologies for personal area network (PAN). Depending on the features of the system to be developed, different technologies need to be deployed. These technologies are supposed to coexist, even though many of them operate in the same 2.4-GHz band. In case of interference, there are safety mechanisms included in the standard. However, these mechanisms do not work exactly as expected in theory. This paper presents an experiment with a real Bluetoothbased ECG system and Zigbee temperature sensors in an environment where a WiFi network is operating. The main novelty of the paper is the real implementation and experiments of all three wireless technologies for both continuous and discrete medical signals. Conclusions and recommendations for reliable operation are given for all three involved technologies.

Seudoainhum secundario a tricotilomania. Reporte de caso y revisión de la literatura / Seudoanhum secundary to trichotillomania. Case report and review

Presentamos el caso de una paciente de 62 años, con cuadro clínico de tres meses de evolución consistente en aparición de surcos dolorosos en pulpejos de dedos de manos, asociados con áreas de alopecia bitemporal de bordes irregulares, con cabellos de diferente longitud, sin otros hallazgos al examen físico y que al interrogatorio se apreció como una paciente ansiosa, que permanentemente se manipula el cuero cabelludo. La biopsia de piel no mostró lesiones y en cuero cabelludo se observaron cambios de tricomalacia. Por las manifestaciones clínicas en dedos y por las áreas de alopecia secundarias, se diagnosticó como seudoainhum, secundario a tracción ejercida por el pelo, descartando previamente otras etiologías. El caso, resalta además, la importancia de la piel como marcador de enfermedad emocional.

Rapid change of quantal size in PC-12 cells detected by neural networks.

The basic building block of synaptic transmission-the number of molecules released per vesicle (quantal size (QS)) often changes with stimulation, but there is no agreement about what factors regulate it. To throw more light on this problem spontaneous quantal release was recorded amperometrically in PC-12 cells. Amperometric current spikes, representing single vesicle release, were detected by thresholding and were separated from spurious events on the basis of their amplitude and time course using a pattern recognition system based on the principal component neural network methods. The frequency of current spikes, their amplitude, quantal size, rise time and decay time were typically non-stationary, even in the absence of stimulation. Their running values changed much more than those of memoryless stationary random data with the same probability density distribution. Irrespective of how much the quantal size, rise and decay times varied, their amplitude dependence remained constant, or changed with a very different time course. In conclusion, the quantal size is highly labile in PC-12 cells. The lability does not appear to result from the changes of fusion pore dynamics or the mechanism of release of vesicular content, but because of the preferential release of large vesicles.

Cytotoxic activity of five compounds isolated from Colombian plants.

Cytotoxic effect of five known compounds, khellin, berberine, lupeol, scopolin, rapanone, obtained from Colombian plants, were determined against human tumor cell lines as an indicator of the potential anticancer activity of these compounds. Berberine and rapanone presented interesting cytotoxicity.

Simulation and parameter estimation of dynamics of synaptic depression.

Synaptic release was simulated using a Simulink sequential storage model with three vesicular pools. Modeling was modular and easily extendable to the systems with greater number of vesicular pools, parallel input, or time-varying parameters. Given an input (short or long tetanic trains, patterned or random stimulation) and the storage model, the vesicular release, the replenishment of various vesicular pools, and the vesicular content of all pools could be simulated for the time-invariant and time-varying storage systems. From the input stimuli and either a noiseless or a noisy output, the parameters of such storage systems could also be estimated using the optimization technique that minimizes in the least square sense the error between the observed release and the predicted release. All parameters of the storage model could be evaluated with sufficiently long input-output data pairs. Not surprisingly, the parameters characterizing the processes near the release locus, such as the fractional release and the size of the immediately available pool and its coupling to the small store, as well as the state variables associated with the immediately available pool, such as its vesicular content and replenishment, could be determined with fewer stimuli. The possibility of estimating parameters with random inputs extends the applicability of the method to in vivo synapses with the physiological inputs. The parameter estimation was also possible under the time-variant, but slowly changing, conditions as well as for open systems that are part of larger vesicular storage systems but whose parameters can either not be reliably determined or are of no interest. The quality of parameter estimation was monitored continuously by comparing the observed and predicted output and/or estimated parameters with the true values. Finally, the method was tested experimentally using the rat phrenic-diaphragm neuromuscular junction.

Characterizing T-cell receptor gamma-variable gene in Aotus nancymaae owl monkey peripheral blood.

Gammadelta T lymphocytes have a heterodimeric complex formed by the association of gamma and delta chains as receptor. Proliferation of this lymphocyte population has been observed, when infection by several pathogens such as Mycobacterium tuberculosis and Plasmodium spp. occurs. The New World Monkey Aotus nancymaae has become a very good experimental model for the immunological and physiopathological study of these infectious agents. The A. nancymaae gamma-variable region was characterized from peripheral blood samples by using cDNA and genomic DNA polymerase chain reaction amplification, DNA sequencing, and dot-blot hybridization techniques. Seventeen different T-cell receptor gamma-variable (TCRGV) sequences were obtained. These sequences were distributed among TCRGV subsets 1, 2, or 3, according to human subset classification. Although no subset 4 amplification was obtained, this subset was detected by dot-blot hybridization. The presence of these 4 subsets resembles the behavior displayed by 'gammadelta-low species' (humans and mice), where high diversity among these lymphocytes can be observed. Homologies greater than 70% were found with respect to humans. Sequence convergence between human and A. nancymaae subsets 1 and 3 highlights Aotus as a promising model for studying these lymphocyte functions.

Wavelet analysis of nonstationary fluctuations of Monte Carlo-simulated excitatory postsynaptic currents.

Tracking spectral changes of rapidly varying signals is a demanding task. In this study, we explore on Monte Carlo-simulated glutamate-activated AMPA patch and synaptic currents whether a wavelet analysis offers such a possibility. Unlike Fourier methods that determine only the frequency content of a signal, the wavelet analysis determines both the frequency and the time. This is owing to the nature of the basis functions, which are infinite for Fourier transforms (sines and cosines are infinite), but are finite for wavelet analysis (wavelets are localized waves). In agreement with previous reports, the frequency of the stationary patch current fluctuations is higher for larger currents, whereas the mean-variance plots are parabolic. The spectra of the current fluctuations and mean-variance plots are close to the theoretically predicted values. The median frequency of the synaptic and nonstationary patch currents is, however, time dependent, though at the peak of synaptic currents, the median frequency is insensitive to the number of glutamate molecules released. Such time dependence demonstrates that the "composite spectra" of the current fluctuations gathered over the whole duration of synaptic currents cannot be used to assess the mean open time or effective mean open time of AMPA channels. The current (patch or synaptic) versus median frequency plots show hysteresis. The median frequency is thus not a simple reflection of the overall receptor saturation levels and is greater during the rise phase for the same saturation level. The hysteresis is due to the higher occupancy of the doubly bound state during the rise phase and not due to the spatial spread of the saturation disk, which remains remarkably constant. Albeit time dependent, the variance of the synaptic and nonstationary patch currents can be accurately determined. Nevertheless the evaluation of the number of AMPA channels and their single current from the mean-variance plots of patch or synaptic currents is not highly accurate owing to the varying number of the activatable AMPA channels caused by desensitization. The spatial nonuniformity of open, bound, and desensitized AMPA channels, and the time dependence and spatial nonuniformity of the glutamate concentration in the synaptic cleft, further reduce the accuracy of estimates of the number of AMPA channels from synaptic currents. In conclusion, wavelet analysis of nonstationary fluctuations of patch and synaptic currents expands our ability to determine accurately the variance and frequency of current fluctuations, demonstrates the limits of applicability of techniques currently used to evaluate the single channel current and number of AMPA channels, and offers new insights into the mechanisms involved in the generation of unitary quantal events at excitatory central synapses.

New solvent-producing Clostridium sp. strains, hydrolyzing a wide range of polysaccharides, are closely related to Clostridium butyricum.

Thirteen new Clostridium strains, previously isolated from soil and found to produce high amounts of solvents from glucose, hydrolyzed a great variety of alpha- and beta-glycans, including raw starch, xylan, pectin, inulin and cellulose. The sequences of the PCR-amplified DNA fragments containing the variable 3' part of one of the 16S rRNA genes were 99.5% identical. The macrorestriction pattern of two endonucleolytic digests of chromosomal DNA in the pulsed-field gel electrophoresis (PFGE) confirmed their high homogeneity on the DNA level. The complete 16S rRNA gene sequence of three selected strains was 99.8% identical to the 16S rRNA gene sequence from Clostridium butyricum and separates them from C. acetobutylicum. To the closely related four species of solventogenic clostridia a new group of strains has to be added, which has a great potential for the direct fermentation of biomass.

Isolation of the LEMMI9 gene and promoter analysis during a compatible plant-nematode interaction.

Plant-endoparasitic root-knot nematodes feed on specialized giant cells that they induce in the vascular cylinder of susceptible plants. Although it has been established that a number of plant genes change their expression pattern during giant cell differentiation, virtually no data are available about the mechanisms involved in that change. One possibility is differential promoter recognition by the transcription factor(s) responsible for the expression of specific genes. We have isolated and characterized a genomic clone from tomato containing the promoter region of LEMMI9, one of the few plant genes that have been reported to be highly expressed in galls (predominantly in giant cells). The analysis of transgenic potato plants carrying a LEMMI9 promoter-beta glucuronidase (GUS) fusion has demonstrated that the tomato promoter was activated in Meloidogyne incognita-induced galls in a heterologous system. We have located putative regulatory sequences in the promoter and have found that nuclear proteins from the galls formed specific DNA-protein complexes with the proximal region of the LEMMI9 promoter. The nuclear protein-binding sequence mapped to a region of 111 bp immediately upstream from the TATA box. This region contains a 12-bp repeat possibly involved in the formation of DNA-protein complexes, which might be related to the LEMMI9 transcriptional activation in the giant cells.