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ObjectiveGATA6 is a master regulator of pancreatic differentiation and a key regulator of the classical phenotype in pancreatic ductal adenocarcinoma (PDAC). Low GATA6 expression is associated with poor patient outcome.GATA4is the second most expressed GATA factor in the pancreas. The aim was to assess whether, and how, GATA4 contributes to PDAC phenotype and to analyze the association of expression with clinical outcome.DesignWe analyzed PDAC transcriptomic data, stratifying cases according toGATA4andGATA6expression, and identified differentially expressed genes and pathways. A multicenter TMA study to assess GATA4 and GATA6 expression in PDAC samples (n=745) from patients undergoing tumour resection was performed using immunohistochemistry with antibodies of validated specificity. GATA4 and GATA6 levels were dichotomized into high/low categorical variables; association with outcome was assessed using univariable and multivariable Cox regression models.ResultsSubtype classification using transcriptomic data revealed thatGATA4mRNA is enriched in classical, compared to basal-like tumours. We classified samples in 4 groups as high/low forGATA4andGATA6. Reduced expression ofGATA4did not have a major transcriptional impact. However, concomitant low expression ofGATA4enhanced the transcriptomic effects ofGATA6low expression. Reduced expression of both proteins in tumours was associated with the worst patient survival.GATA4andGATA6expression significantly decreased in metastases and negatively correlated with basal markers.ConclusionsOur analyses uncover a cooperative interaction betweenGATA4andGATA6to maintain the classical PDAC phenotype and provide compelling clinical rationale for assessing their expression as biomarkers of poor prognosis.SUMMARY BOXWhat is already known about this subject?-Patients with classical-type PDAC have a better outcome-Retrospective analyses suggest that classical-type PDAC is more sensitive to 5-FU-based chemotherapy-GATA6 is a surrogate biomarker of classical tumours and its expression is associated with better survival-GATA4 and GATA6 have overlapping and unique functions during pancreatic and gastrointestinal developmentWhat are the new findings?-Tumours displaying only low GATA4 expression have a transcriptomic profile similar to those with preserved expression of both transcription factors-Combined low expression of GATA4 and GATA6 has the highest transcriptomic impact-In a large multicenter tissue microarray study, patients with tumours showing low expression of both GATA4 and GATA6 have the worst overall survival-Low expression of GATA4 and GATA6 is an independent predictor of survival in patients with resectable PDAC-GATA4 levels are down-regulated in liver metastases and are negatively correlated with basal markers such as KRT5/6, KRT14, and TP63How might it impact on clinical practice in the foreseeable future?-The combined assessment of GATA4 and GATA6 expression may improve prognostic stratification of patients with PDAC-Prospective studies should confirm whether GATA4 and GATA6 expression is also predictive of response to chemotherapy in PDAC patients

We sought to evaluate the relative value of pure tone audiometry (PTA), extended high-frequency audiometry (EFA) and transiently evoked otoacoustic emissions (OAE) and distortion products when monitoring acute acoustic trauma (AAT).Controlled prospective clinical study.Tertiary referral center.Seventy one active duty soldiers in the same age with normal hearingForty one soldiers suffered assault-rifle-induced acute acoustic traumas with hearing loss and tinnitus. Thirty soldiers served as a control group.Pure tone threshold changes detected by PTA and EFA, amplitude and reproducibility changes in transiently evoked OAE, distortion products, and tinnitus analysis based on a visual analog scale.Assault rifle-induced AAT caused unilateral temporary threshold shifts (TTS) in PTA and bilateral TTS in EFA. Two frequency regions with the largest threshold shifts were identified: one between 3 and 6 kHz and another between 11 and 14 kHz. The reproducibility of transiently evoked OAEs revealed changes related to the acoustic trauma in the 3- to 5-kHz frequency window. The amplitudes of the low stimulation level distortion products at 6 kHz were correlated with the audiometric AAT-induced TTS.Acute acoustic trauma-induced audiometric TTS are predominantly confined to 2 specific frequency regions. PTA and EFA are both necessary to identify the full extent of acute acoustic trauma. PTA and EFA revealed that the TTSs were correlated to with distortion product OAE amplitude shifts at 6 kHz and changes in the reproducibility of transiently evoked OAE in the 3- to 5-kHz frequency window. PTA remains the most important measurement to monitor AAT. It may be useful to complement it with EFA, focusing on the 11 to 14 kHz frequency range. If used, OAE should be analyzed in the frequency range of 3 to 6 kHz.

BackgroundLiving-related liver transplantation has become an excellent treatment method for patients with end-stage liver disease. The anatomical variation is the corner stone for donor and recipient safety.Aim of the studyTo evaluate the impact of anatomical variations of the donor's liver on the p

Background & Aims: Secretions from the exocrine and endocrine pancreas may modulate interdigestive motility. To test this hypothesis in humans, we investigated interdigestive cycling in patients with chronic pancreatitis (CP) as a model of impaired pancreatic function. Methods: Antroduodenal motility, pancreatic enzyme output, and pancreatic polypeptide release were monitored for two consecutive interdigestive cycles in 13 controls and 9 patients with CP. Results: Interdigestive enzyme output was severely impaired in patients with CP (>80% decrease); however, secretory cycling was still evident in most patients. All parameters describing interdigestive motility were similar in controls and patients with CP (duration of the migrating motor complex [MMC] was 107 ± 19 minutes in patients with CP vs. 114 ± 15 minutes in controls). The time between cyclic peaks of enzyme secretion (76 ± 4 minutes vs. 101 ± 4 minutes in controls) and pancreatic polypeptide (63 ± 4 minutes vs. 106 ± 7 minutes in controls) was shortened in patients with CP, and peaks were no longer temporally related to the MMC. Only 56% of phase III activity fronts were associated with a concomitant secretory peak in patients with CP compared with 92% in healthy subjects. Conclusions: CP not only decreases pancreatic secretion but interrupts the coordination among interdigestive cyclic phenomena. Our findings in several animal and human models refute the concept that pancreatic mechanisms exert a major regulatory influence on interdigestive motor activity.

BACKGROUND: In tuberculosis (TB), the risk of exposure is determined mainly by the proximity to and the hours of direct contact with an infectious patient. We describe the contact investigation after detection of an infectious form of TB in a military camp using an Interferon-g-Release-Assay (IGRA, QuantiFERON-TB Gold In Tube [QTF-GIT]) eight weeks after detection of the index case. INDEX PATIENT: The index patient presented with fever, cough and weight loss in the military hospital six weeks after entering the camp. TB was suspected and anti-tuberculous therapy given immediately. Subsequently, TB was microbiologically confirmed. METHODS: Four exposure groups were formed a priori based on the proximity and the hours of direct contact to the index case. 168 (95.5%) agreed to be investigated: - Group A: sharing the same dormitory (15 persons) - Group B: same platoon, but not sharing the dormitory (20 persons) - Group C: staff and patients of the military hospital (22 persons) - Group D: other three platoons and senior military staff (111 persons). RESULTS: 34 (20.2%) out of 168 contacts tested positive in the QFT-GIT assay. For the exposure groups, the respective QFT-GIT testing results were: group A, 14/15 (93%); group B, 4/20 (20%); group C, 5/22 (22.7%); and group D, 11/111 (9.9%). No secondary TB cases were identified. CONCLUSIONS: In our study, test results show a correlation with the risk of exposure, suggesting that IGRA may be useful for the assessment of TB infection in TB contacts. The high mobility of recruits reduced traceability of contacts. In this context, QFT-GIT allowed for an efficient screening of contacts at a single time point.

A simple implementation of modulation of the near-field optical signal of near-field probes based on the shear-force feedback system is demonstrated in a reflection-mode near-field optical microscope. The modulation exhibits a derivative type of dependence on the near-field signal and no sensitivity to topography. It is shown that the modulation image can be calculated directly from the derivative of the conventional near-field scattering image. This type of near-field modulation is an excellent way to reject far-field artifacts from the near-field signal.

New methods of assessment of enzyme activity - do they help to optimize enzyme treatment?, G. Adler et al fate of pancreatic enzymes in the human intestinal lumen in health and pancreatic insufficiency, P. Layer and G. Groger effect of exogenous pancreatic enzymes on gastrointestinal and pancreatic hormone release and gastrointestinal motility, P. Malfertheiner and J.E. Dominguez-Monoz enzyme treatment of exocrine pancreatic insufficiency in chronic pancreatitis, P.G. Lankisch pancreatic pain - is there a place for pancreatic enzymes in the treatment of pain in chronic pancreatitis?, I. Ihse et al acute pancreatitis - when is enzyme treatment indicated?, M.J. McMahon indication for pancreatic enzyme treatment in non-pancreatic digestive diseases, L. Gullo enzyme treatment after gastrointestinal surgery, H. Friess et al.