Transcriptional regulation of osmotic stress tolerance in wheat (Triticum aestivum L.).

KEY MESSAGE: The current review provides an updated, new insights into the regulation of transcription mediated underlying mechanisms of wheat plants to osmotic stress perturbations. Osmotic stress tolerance mechanisms being complex are governed by multiple factors at physiological, biochemical and at the molecular level, hence approaches like "OMICS" that can underpin mechanisms behind osmotic tolerance in wheat is of paramount importance. The transcription factors (TFs) are a class of molecular proteins, which are involved in regulation, modulation and orchestrating the responses of plants to a variety of environmental stresses. Recent reports have provided novel insights on the role of TFs in osmotic stress tolerance via direct molecular links. However, our knowledge on the regulatory role TFs during osmotic stress tolerance in wheat remains limited. The present review in its first part sheds light on the importance of studying the role of osmotic stress tolerance in wheat plants and second aims to decipher molecular mechanisms of TFs belonging to several classes, including DREB, NAC, MYB, WRKY and bHLH, which have been reported to engage in osmotic stress mediated gene expression in wheat and third part covers the systems biology approaches to understand the transcriptional regulation of osmotic stress and the role of long non-coding RNAs in response to osmotic stress with special emphasis on wheat. The current concept may lead to an understanding in molecular regulation and signalling interaction of TFs under osmotic stress to clarify challenges and problems for devising potential strategies to improve complex regulatory events involved in plant tolerance to osmotic stress adaptive pathways in wheat.

Clinical profile and treatment outcomes of advanced neuroendocrine tumours in rural and regional patients: a retrospective study from a regional cancer centre in North Queensland, Australia.

BACKGROUND: Neuroendocrine tumours (NET) arise from neuroendocrine cells, which are widely distributed throughout the body. However, diagnosing NET is difficult due to nonspecific symptoms and the paucity of experience among health professionals. This retrospective study was carried out to improve our understanding about NET. This knowledge can be used for optimal utilisation and distribution of limited resources. AIM: To study the clinical profile, treatment and survival outcomes for advanced NET patients in Australian regional and remote settings. METHODS: We reviewed all adult patients who were diagnosed with NET between 1994 and 2012. Patients' data were extracted from electronic databases of The Townsville Cancer Centre. Remoteness was based on postcodes, with patients stratified as regional or rural North Queensland according to Australian Standard Geographical Classification (ASGC). Overall survival was studied using survival analysis. RESULTS: Data from 79 patients were included in the study. The median age at diagnosis was 60 years. A total of 48 patients (60.8%) was male and 31 (39.2%) female. The majority of the patients lived in rural areas (51, 64%) as compared to residing in regional areas (28, 36%). There were 34 deaths at the study cut-off point. Median overall survival of NET patients in rural areas is significantly less than those living in regional areas (1613 days vs. 2935 days, respectively), P = 0.03. CONCLUSION: Remoteness has an adverse impact on overall survival of NET patients. This outcome may be because of varied access to health services and/or lack of access to specialised scans and medical and surgical expertise.

Comparison of objective criteria and expert visual interpretation to classify benign and malignant hilar and mediastinal nodes on 18-F FDG PET/CT.

BACKGROUND AND OBJECTIVE: There is widespread adoption of FDG-PET/CT in staging of lung cancer, but no universally accepted criteria for classifying thoracic nodes as malignant. Previous studies show high negative predictive values, but reporting criteria and positive predictive values varies. Using Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) results as gold standard, we evaluated objective FDG-PET/CT criteria for interpreting mediastinal and hilar nodes and compared this to expert visual interpretation (EVI). METHODS: A retrospective review of all patients with lung cancer who had both FDG-PET/CT and EBUS-TBNA from 2008 to 2010 was performed. Scan interpretation was blinded to histology. Patients from 2008/2009 were used for the prediction set. The validation set analysed patients from 2010. Objective FDG-PET/CT criteria were SUVmax lymph node (SUVmaxLN), ratio SUVmaxLN/SUVmax primary lung malignancy, ratio SUVmaxLN/SUVaverage liver, ratio SUVmaxLN/SUVmax liver and ratio SUVmaxLN/SUVmax blood pool. A nuclear medicine physician reviewed all scans and classified nodal stations as benign or malignant. RESULTS: Eighty-seven malignant lymph nodes and 41 benign nodes were in the prediction set. All objective FDG-PET/CT criteria analysed were significantly higher in the malignant group (P < 0.0001). EVI correctly classified 122/128 nodes (95.3%). Thirty-four malignant nodes and 19 benign nodes were in the validation set. The new proposed cut-off values of the objective criteria from the prediction set correctly classified 44/53 (83.0%) nodes: 28/34 (82.4%) malignant nodes and 16/19 (84.2%) benign nodes. EVI had 91% accuracy: 33/34 (97.1%) malignant nodes and 15/19 (79.0%) benign nodes. CONCLUSIONS: Objective analysis of 18-F FDG PET/CT can differentiate between malignant and benign nodes but is not superior to EVI.

Comparative lung distribution of radiolabeled tobramycin between nebulized and intravenous administration in a mechanically-ventilated ovine model, an observational study.

BACKGROUND: Ventilator-associated pneumonia is common and is treated using nebulized antibiotics. Although adequate pulmonary biodistribution is important for antibiotic effect, there is a lack of data for both intravenous (IV) and nebulized antibiotic administration during mechanical ventilation. OBJECTIVE: To describe the comparative pulmonary regional distribution of IV and nebulized technetium-99m-labeled tobramycin (99mTc-tobramycin) 400 mg in a mechanically-ventilated ovine model. METHODS: The study was performed in a mechanically-ventilated ovine model. 99mTc-tobramycin 400 mg was obtained using a radiolabeling process. Computed tomography (CT) was performed. Ten sheep were given 99mTc-tobramycin 400 mg via either an IV (five sheep) or nebulized (five sheep) route. Planar images (dorsal, ventral, left lateral and right lateral) were obtained using a gamma camera. Blood samples were obtained every 15 min for 1 h (4 time points) and lung, liver, both kidney, and urine samples were obtained post-mortem. RESULTS: Ten sheep were anesthetized and mechanically ventilated. Whole-lung deposition of nebulized 99mTc-tobramycin 400 mg was significantly lower than with IV (8.8% vs. 57.1%, P<0.001). For both administration routes, there was significantly lower deposition in upper lung zones compared with the rest of the lungs. Dorsal deposition was significantly higher with nebulized 99mTc-tobramycin 400 mg compared with IV (68.9% vs. 58.9%, P=0.003). Lung concentrations of 99mTc-tobramycin were higher with IV compared with nebulized administration. There were significantly higher concentrations of 99mTc-tobramycin in blood, liver and urine with IV administration compared with nebulized. CONCLUSIONS: Nebulization resulted in lower whole and regional lung deposition of 99mTc-tobramycin compared with IV administration and appeared to be associated with low blood and extra-pulmonary organ concentrations.

A research pathway for the study of the delivery and disposition of nebulised antibiotics: an incremental approach from in vitro to large animal models.

BACKGROUND: Nebulised antibiotics are frequently used for the prevention or treatment of ventilator-associated pneumonia. Many factors may influence pulmonary drug concentrations with inaccurate dosing schedules potentially leading to therapeutic failure and/or the emergence of antibiotic resistance. We describe a research pathway for studying the pharmacokinetics of a nebulised antibiotic during mechanical ventilation using in vitro methods and ovine models, using tobramycin as the study antibiotic. METHODS: In vitro studies using a laser diffractometer and a bacterial-viral filter were used to measure the effect of the type and size of tracheal tubes and antibiotic concentration on the particle size distribution of the tobramycin 400 mg (4 ml; 100 mg/ml) and 160 mg (4 ml, 40 mg/ml) aerosol and nebulised mass delivered. To compare the regional drug distribution in the lung of two routes (intravenous and nebulised) of drug administration of tobramycin 400 mg, technetium-99m-labelled tobramycin 400 mg with planar nuclear medicine imaging was used in a mechanically ventilated ovine model. To measure tobramycin concentrations by intravenous and nebulised tobramycin 400 mg (4 ml, 100 mg/ml) administration in the lung interstitial space (ISF) fluid and blood of mechanically ventilated sheep, the microdialysis technique was used over an 8-h duration. RESULTS: Tobramycin 100 mg/ml achieved a higher lung dose (121.3 mg) compared to 40 mg/ml (41.3 mg) solution. The imaging study with labelled tobramycin indicated that nebulised tobramycin distributed more extensively into each lung zone of the mechanically ventilated sheep than intravenous administration. A higher lung ISF peak concentration of tobramycin was observed with nebulised tobramycin (40.8 mg/l) compared to intravenous route (19.0 mg/l). CONCLUSIONS: The research methods appear promising to describe lung pharmacokinetics for formulations intended for nebulisation during mechanical ventilation. These methods need further validation in an experimental pneumonia model to be able to contribute toward optimising dosing regimens to inform clinical trials and/or clinical use.

Prostate-Specific Membrane Antigen PET/CT Findings for Hepatic Hemangioma.

We report a case of a benign liver hemangioma with intense prostate-specific membrane antigen (PSMA) uptake on Ga PET/CT. A 77-year-old man with prostate adenocarcinoma underwent routine staging with PSMA PET/CT. This revealed an intensely PSMA-avid liver lesion. The known prostate adenocarcinoma was localized and had mild uptake. Diagnostic CT and MRI were characteristic of a hemangioma without interval growth over a 3-month period. PSMA PET/CT is becoming increasingly popular for staging in prostate cancer, and the presence of PSMA uptake in extra-prostatic tumors is being increasingly documented.

FDG PET/CT appearance of benign pilomatricoma.

A 56-year-old patient was referred for FDG PET/CT with a right preauricular lymph node fine-needle biopsy, suggesting poorly differentiated carcinoma and no obvious primary lesion. There was intense FDG uptake in the right preauricular nodule. The node was excised, and formal histology demonstrated a benign pilomatricoma rather than malignancy. Pilomatricoma is uncommon in adults and an unusual cause for marked FDG uptake, likely due to foreign body inflammation. Pilomatricoma can be either benign or malignant. The marked FDG uptake demonstrated in our patient with benign pilomatricoma also suggests that FDG PET cannot reliably grade this rare condition.

Optical differentiation between malignant and benign lymphadenopathy by grey scale texture analysis of endobronchial ultrasound convex probe images.

BACKGROUND: Morphologic and sonographic features of endobronchial ultrasound (EBUS) convex probe images are helpful in predicting metastatic lymph nodes. Grey scale texture analysis is a well-established methodology that has been applied to ultrasound images in other fields of medicine. The aim of this study was to determine if this methodology could differentiate between benign and malignant lymphadenopathy of EBUS images. METHODS: Lymph nodes from digital images of EBUS procedures were manually mapped to obtain a region of interest and were analyzed in a prediction set. The regions of interest were analyzed for the following grey scale texture features in MATLAB (version 7.8.0.347 [R2009a]): mean pixel value, difference between maximal and minimal pixel value, SEM pixel value, entropy, correlation, energy, and homogeneity. Significant grey scale texture features were used to assess a validation set compared with fluoro-D-glucose (FDG)-PET-CT scan findings where available. RESULTS: Fifty-two malignant nodes and 48 benign nodes were in the prediction set. Malignant nodes had a greater difference in the maximal and minimal pixel values, SEM pixel value, entropy, and correlation, and a lower energy (P < .0001 for all values). Fifty-one lymph nodes were in the validation set; 44 of 51 (86.3%) were classified correctly. Eighteen of these lymph nodes also had FDG-PET-CT scan assessment, which correctly classified 14 of 18 nodes (77.8%), compared with grey scale texture analysis, which correctly classified 16 of 18 nodes (88.9%). CONCLUSIONS: Grey scale texture analysis of EBUS convex probe images can be used to differentiate malignant and benign lymphadenopathy. Preliminary results are comparable to FDG-PET-CT scan.

Correlation of various published radionuclide glomerular filtration rate estimation techniques and proposed paediatric normative data.

OBJECTIVE: The aim of this study is to assess the comparability and interchangeability of the radionuclide glomerular filtration rate (GFR) using different published techniques, and propose normative data for paediatrics. METHODS: A total of 476 paediatric oncology patients aged 2-17 years, referred between January 2001 and December 2008 for GFR estimation, were reviewed for any potential cause of renal impairment. Sixty-nine patients met the stringent inclusion criteria, and were included in the study. GFR estimation was carried out using either technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) or chromium-51 EDTA (5¹Cr-EDTA). Multiple GFR results were calculated from the same blood sample data (counts/min/ml), according to previously published GFR estimation techniques using one to three blood samples. These techniques were slope-intercept, slope-only and half life. For slope-intercept techniques, GFR was normalized to body surface area or extracellular fluid volume. RESULTS: The GFR values obtained using different techniques were highly variant. The intraclass correlation (ICC) for different methods was moderate (ICC=0.56-0.66). A reliable empiric formula to allow conversion of GFR values from one technique to another could not be derived because of this variability, with some exceptions. 5¹Cr-EDTA yielded the same or lower variability than 99mTc-DTPA. The British Nuclear Medicine Society-recommended method had the lowest coefficient of variation, with a mean value of 116 (SD 22) normalized to 1.73 m² for 5¹Cr-EDTA using two samples. CONCLUSION: The GFR values obtained from different calculation techniques are not readily interchangeable or comparable, with some exceptions. For both 99mTc-DTPA and 5¹Cr-EDTA, the British Nuclear Medicine Society-recommended technique appears to be the most robust, with the least coefficient of variation.