Improved algorithm with adaptive regularization for tomographic reconstruction of gas distributions using DOAS measurements.

Differential optical absorption spectroscopy (DOAS) is notably well suited for the retrieval of UV-absorbing trace gases present in the atmosphere. We combine multi-axis DOAS observations to perform a tomographic reconstruction of the distribution of gases emitted from different sources. We use a new algorithm based on a regularized minimization approach embedding key physical aspects of the solution to constrain the inversion. In this work, we take into account that the spatial sampling of the plume being scanned by the instruments is not homogeneous. Therefore, we introduce an adaptive approach with a locally tuned regularization weight according to the uncertainty levels introduced by the sampling scheme. We tested our approach on reconstructions of simulated gas distributions and different configurations applicable to multi-axis DOAS. Finally, our approach is applied to experimental data for the retrieval of the distribution of ${\rm NO}_2$NO2 within a plume cross section emitted from a group of stacks.

Effect of rMnSOD on survival signaling in pediatric high risk T-cell acute lymphoblastic leukaemia.

Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that defends against oxidative damage due to reactive oxygen species (ROS). A new isoform of MnSOD with cytotoxic activity was recently discovered in liposarcoma cells. Here, we tested the effectiveness of a recombinant form of this isoform (rMnSOD) on leukemic T cells, Jurkat cells, and lymphocytes. Our results confirm that leukemic T cells can internalize rMnSOD and that rMnSOD causes apoptosis of 99% of leukemic cells without showing toxic effects on healthy cells. Using light and electron microscopy, we determined that an rMnSOD concentration of 0.067 µM most effective on apoptosis induction. Western blot analysis showed that treatment with 0.067 µM rMnSOD resulted in high expression of the pro-apoptotic protein Bax and low expression of the anti-apoptotic protein Bcl-2 in leukemia cells. Concerning signal transduction pathway no influence was observed after treatment except for Jurkat cells showing a slightly decreased expression of ERK phosphorylation. These results suggest that rMnSOD may be an effective and non-toxic treatment option for T-cell leukemia.

A double-blind, placebo-controlled randomized trial to evaluate the efficacy of docosahexaenoic acid supplementation on hepatic fat and associated cardiovascular risk factors in overweight children with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Very little information is available on whether docosahexaenoic acid (DHA) supplementation has a beneficial effect on liver fat and cardiovascular disease (CVD) risk factors in children with nonalcoholic fatty liver disease (NAFLD). In a double-blind, placebo-controlled randomized trial we investigated whether 6-month treatment with DHA improves hepatic fat and other fat depots, and their associated CVD risk factors in children with biopsy-proven NAFLD. METHODS AND RESULTS: Of 58 randomized children, 51 (25 DHA, 26 placebo) completed the study. The main outcome was the change in hepatic fat fraction as estimated by magnetic resonance imaging. Secondary outcomes were changes in visceral adipose tissue (VAT), epicardial adipose tissue (EAT), and left ventricular (LV) function, as well as alanine aminotransferase (ALT), triglycerides, body mass index-standard deviation score (BMI-SDS), and insulin sensitivity. At 6 months, the liver fat was reduced by 53.4% (95% CI, 33.4-73.4) in the DHA group, as compared with 22.6% (6.2-39.0) in the placebo group (P = 0.040 for the comparison between the two groups). Likewise, in the DHA group VAT and EAT were reduced by 7.8% (0-18.3) and 14.2% (0-28.2%), as compared with 2.2% (0-8.1) and 1.7% (0-6.8%) in the placebo group, respectively (P = 0.01 for both comparisons). There were no significant between-group changes for LV function as well as BMI-SDS and ALT, while fasting insulin and triglycerides significantly decreased in the DHA-treated children (P = 0.028 and P = 0.041, respectively). CONCLUSIONS: DHA supplementation decreases liver and visceral fat, and ameliorates metabolic abnormalities in children with NAFLD.

Evaluation of image quality, radiation dose and diagnostic performance of dual-energy CT datasets in patients with hepatocellular carcinoma.

AIM: To evaluate image quality and diagnostic accuracy of different dual-energy computed tomography (DECT) datasets for identification of hepatocellular carcinoma (HCC), assess the reliability of virtual unenhanced (VU) images in replacing standard unenhanced (SU) images, and quantify effective dose (ED) at different tube voltages. MATERIAL AND METHODS: Thirty cirrhotic patients underwent liver contrast-enhanced DECT. Two blinded observers retrospectively evaluated conventional unenhanced and VU images, 140 kVp/80 kVp/mixed tube potential arterial datasets and conventional portal-venous/late phases in consensus. Final diagnosis was based on pathological proof or imaging criteria. Image quality, ED, sensitivity, and specificity of arterial datasets were calculated. RESULTS: Thirty-eight HCC and 18 benign lesions were detected at 80 kVp, 33 HCC and 22 benign lesions were detected at 140 kVp, and 36 HCC and 20 benign lesions were detected at mixed tube potentials. Final diagnosis confirmed 37 HCC and 20 benign lesions. There was no significant difference in diagnostic confidence between 80 kVp, 140 kVp, and mixed tube potential arterial datasets (p>0.05). Image quality was adequate for all datasets, with increased quality at higher tube potential (80 versus 140 kVp, p=0.001; mixed versus 140 kVp, p=0.001; 80 kVp versus mixed, p=0.0024). Significant ED reduction was observed between 140 and 80 kVp datasets (p<0.001). CONCLUSIONS: The 140 kVp dataset provided higher image quality. The 80 kVp images were more sensitive in detecting HCC. VU images are adequate in replacing SU images. The ED of the 80 kVp dataset was significantly lower.

Soy isoflavones, inulin, calcium, and vitamin D3 in post-menopausal hot flushes: an observational study.

PURPOSE OF INVESTIGATION: To evaluate the effect of soy isoflavones and inulin (SII) on hot flushes (HF) and quality of life in a clinical setting, the authors conducted an observational study. MATERIALS AND METHODS: The authors performed an observational, prospective, multicentric study on women in peri-/post-menopause treated or untreated with a product present on the Italian market, consisting in a mixture of calcium (500 mg), vitamin D3 (300 IU), inulin (3 g) and soy isoflavones (40 mg). RESULTS: A total of 135 patients, 75 (55.6%) in the SII group and 60 (44.4%) in the untreated group entered the study. After three months, the mean number of HF declined of 2.8 (SD 3.7) in the SII group and 0.0 in the untreated one. The corresponding values after six months were -3.7 (SD 2.7) in the SII group and -0.9 (SD 5.3) in the control group (p = 0.02). CONCLUSION: This observational trial suggests a possible beneficial effect of a dietary soy supplement containing 40 mg of isoflavone/day plus inulin in the management of menopausal symptoms such as hot flashes.

Arterial function and structure after a 1-year lifestyle intervention in children with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Lifestyle modification has been the mainstay of controlling childhood obesity and has proved to be effective in reducing cardiovascular risk factors. However, it is currently unknown whether the subclinical atherosclerotic changes associated with nonalcoholic fatty liver disease (NAFLD) in such population are reversible. METHODS AND RESULTS: We analyzed changes of brachial flow-mediated dilation (FMD), carotid intima-media thickness (cIMT), clinical, laboratory, and imaging data in 120 obese children with NAFLD, at the end of a 1-year intervention program with diet and physical exercise. The lifestyle intervention led to a significant mean decrease of body mass index (BMI)-standard deviation score (SDS), waist circumference (WC) and fat mass, along with diastolic blood pressure, triglycerides, liver enzymes, insulin, insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR), and high-sensitivity C-reactive protein. At the end of the study, FMD improved (P < 0.0001), while cIMT did not change significantly (P = 0.20). A significant decrease in hepatic fat content as measured by magnetic resonance imaging was also observed. Changes in FMD were inversely associated with changes in BMI-SDS, WC, total cholesterol, non-HDL cholesterol, liver enzymes, HOMA-IR, physical activity, and hepatic fat content. After including in the model all the significant variables as well as age, gender, pubertal status, and baseline FMD values, changes in FMD were significantly and independently associated with changes in WC and total cholesterol. CONCLUSION: Also in obese children with NAFLD arterial function may be restored by improving metabolic risk factors and reducing visceral adiposity following a 1-year lifestyle intervention.

Liver resection and ablation for squamous cell carcinoma liver metastases.

BACKGROUND: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS). METHOD: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS. RESULTS: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30). CONCLUSION: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome.

Diagnostic accuracy of translucency rendering to differentiate polyps from pseudopolyps at 3D endoluminal CT colonography: a feasibility study.

PURPOSE: The aim of this study was to assess the accuracy of translucency rendering (TR) in computed tomographic (CT) colonography without cathartic preparation using primary 3D reading. MATERIALS AND METHODS: From 350 patients with 482 endoscopically verified polyps, 50 pathologically proven polyps and 50 pseudopolyps were retrospectively examined. For faecal tagging, all patients ingested 140 ml of orally administered iodinated contrast agent (diatrizoate meglumine and diatrizoate sodium) at meals 48 h prior to CT colonography examination and two h prior to scanning. CT colonography was performed using a 64-section CT scanner. Colonoscopy with segmental unblinding was performed within 2 weeks after CT. Three independent radiologists retrospectively evaluated TRCT clonographic images using a dedicated software package (V3D-Colon System). To enable size-dependent statistical analysis, lesions were stratified into the following size categories: small (< or =5 mm), intermediate (6-9 mm), and large (> or =10 mm). RESULTS: Overall average TR sensitivity for polyp characterisation was 96.6%, and overall average specificity for pseudopolyp characterisation was 91.3%. Overall average diagnostic accuracy (area under the curve) of TR for characterising colonic lesions was 0.97. CONCLUSIONS: TR is an accurate tool that facilitates interpretation of images obtained with a primary 3D analysis, thus enabling easy differentiation of polyps from pseudopolyps.

Left-sided portal hypertension due to retroperitoneal fibrosis treated with an oesophagus preserving, modified Sugiura procedure.

Left-sided portal hypertension is a very uncommon condition and retroperitoneal fibrosis has rarely been reported as a cause. We present the case of a 77-year-old man with retroperitoneal fibrosis obstructing the splenic vein and causing recurrent episodes of upper gastrointestinal bleeding. Computed tomography showed a retroperitoneal mass as being responsible for the obstruction of the splenic vein, splenomegaly, and diffuse varices around the gastrosplenic and gastrohepatic ligaments. An oesophagus preserving, modified Sugiura procedure was performed with disconnection of the gastric vessels on the lesser curve of the stomach, preserving the pylorus branches of the nerves of Latarjet.

Anthropogenic debris in the digestive tract of a southern right whale (Eubalaena australis) stranded in Golfo Nuevo, Argentina.

Over the past fifty years, interactions between anthropogenic debris and a wide range of marine species have increased. In cetaceans, the most frequent interactions have occurred through ingestion and/or entanglement, with results ranging from minor injuries to death in affected animals. While debris ingestion is widely documented in odontocetes, records are scarcer in mysticetes. This study describes the finding of plastic litter in the digestive tract of a southern right whale (Eubalaena australis) juvenile male, which was found dead on the shores of Golfo Nuevo, Chubut, Argentina in 2014. During the examination of intestinal contents, anthropogenic waste was found and classified as macro-debris (25 mm-1 m). Although this whale likely died of causes not related to this finding, it is the first record of anthropogenic debris ingestion for this species. This event adds information about the potential impact of human-made debris on a variety of aquatic species and ecosystems.

Conservative Management of Gallstone Disease in the Elderly Population: Outcomes and Recurrence.

BACKGROUND & AIMS: The prevalence of gallstone disease increases with age, being early cholecystectomy the most accepted treatment in the vast majority of patients in order to prevent complications and recurrence. The aim of this study is to determine the recurrence rate and its possible predictors after initial non-operative management. MATERIALS AND METHODS: We reviewed a consecutive series of patients, older than 65 years, admitted for a gallstone-related disease and treated with a non-operative management between January 2010 and December 2013. We analyzed comorbidities, clinical data, diagnosis, management, recurrence, and its treatment. Median follow-up after the discharge was 2 years. Recurrence was analyzed by a Kaplan-Meier survival curve. Possible recurrence's predictors were analyzed. RESULTS: The study included 226 patients. Mean age was 80.4 ± 7.2 years, 127 (56%) were female. The main causes of index hospitalization were acute cholecystitis (58%) and biliary pancreatitis (18.1%). After 2 years of follow-up, the recurrence rate was 39.8%; mean time to recurrence was 255.2 ± 42.1 days, 81% of patients recurred within 1 year. Bile duct disease implied a higher recurrence rate than the gallbladder disease group (52% vs 33%, p < 0.001). Subjects with two or more diagnoses during index admission presented higher recurrence rate (32% vs 49%, p < 0.001). CONCLUSION: More than a third of elderly patients could present a recurrence within 2 years after initial non-operative management. Early cholecystectomy should be considered at index admission in order to prevent recurrence.

Elastofibroma dorsi: three cases of personal experience.

Elastofibroma dorsi is a rare, slow growing, soft tissue lesion, which occurs mainly in elderly women, typical located in the infrascapular region. This lesion is characterized by a poorly defined solid mass of fibro-elastic and fatty tissue, enlarging into intermuscular spaces. Elastofibroma may simulate an aggressive behaviour, and differential diagnosis with malignant tumors is sometimes difficult. Surgical resection is generally recommended in symptomatic lesions or in the suspicion of malignancy. We report our experience of three cases of elastofibroma, two of which typically located in the infrascapular region and one located in the supra-clavicle fossa, atypical site never reported so far.

Initial clinical outcomes and prognostic variables in the implementation of a Code Sepsis in a high complexity University Hospital.

OBJECTIVE: To assess the impact of the first months of application of a Code Sepsis in a high complexity hospital, analyzing patient´s epidemiological and clinical characteristics and prognostic factors. METHODS: A long-term observational study was carried out throughout a consecutive period of seven months (February 2015 - September 2015). The relationship with mortality of risk factors, and analytic values was analyzed using uni- and multivariate analyses. RESULTS: A total of 237 patients were included. The in-hospital mortality was 24% at 30 days and 27% at 60 days. The mortality of patients admitted to Critical Care Units was 30%. Significant differences were found between the patients who died and those who survived in mean levels of creatinine (2.30 vs 1.46 mg/dL, p <0.05), lactic acid (6.10 vs 2.62 mmol/L, p <0.05) and procalcitonin (23.27 vs 12.73 mg/dL, p<0.05). A statistically significant linear trend was found between SOFA scale rating and mortality (p<0.05). In the multivariate analysis additional independent risk factors associated with death were identified: age > 65 years (OR 5.33, p <0.05), lactic acid > 3 mmol/L (OR 5,85, p <0,05), creatinine > 1,2 mgr /dL (OR 4,54, p <0,05) and shock (OR 6,57, P <0,05). CONCLUSIONS: The epidemiological, clinical and mortality characteristics of the patients in our series are similar to the best published in the literature. The study has identified several markers that could be useful at a local level to estimate risk of death in septic patients. Studies like this one are necessary to make improvements in the Code Sepsis programs.

Transcutaneous electrical nerve stimulation to treat vestibulodynia: a randomised controlled trial.

OBJECTIVE: To assess the efficacy of transcutaneous electrical nerve stimulation (TENS) in the treatment of vestibulodynia. DESIGN: Double-arm randomised placebo-controlled trial. SETTING: An outpatient department for vulval disease. POPULATION: Forty women with vestibulodynia, a vestibular discomfort mostly reported as a burning pain, occurring in the absence of relevant visible findings or a specific, clinically identifiable, neurological disorder. METHODS: Twice a week active TENS or sham treatment were delivered through a vaginal probe via a calibrated dual channel YSY-EST device. Women of both groups underwent 20 treatment sessions. MAIN OUTCOME MEASURES: Visual analogue scale (VAS), the short form of the McGill-Melzack Pain Questionnaire (SF-MPQ), the Marinoff Scale for dyspareunia and the Female Sexual Function Index questionnaire (FSFI) were assessed at baseline, at the end of treatment and at follow up 3 months after the end of treatment. RESULTS: The VAS and SF-MPQ scores (6.2 +/- 1.9 and 19.5 +/- 11.9 before treatment, respectively) improved significantly in the active TENS group (2.1 +/- 2.7, P= 0.004 and 8.5 +/- 10.7, P= 0.001, respectively), but not in the placebo group. The Marinoff dyspareunia scale and the FSFI also showed a significant improvement. CONCLUSIONS: TENS is a simple, effective and safe short-term (3 months) treatment for the management of vestibulodynia.

Objective assessment of gastroesophageal reflux after extended Heller myotomy and total fundoplication for achalasia with the use of 24-hour combined multichannel intraluminal impedance and pH monitoring (MII-pH).

This study aims to evaluate by the use of 24-hour combined multichannel intraluminal impedance and pH monitoring (MII-pH) the efficacy of the Nissen fundoplication in controlling both acid and nonacid gastroesophageal reflux (GER) in patients that underwent Heller myotomy for achalasia. It has been demonstrated that fundoplication prevents the pathologic acid GER after Heller myotomy, but no objective data exists on the efficacy of this antireflux surgery in controlling all types of reflux events. The study population consisted of 20 patients that underwent laparoscopic Heller myotomy and Nissen fundoplication for achalasia. All patients were investigated with manometry and MII-pH. MII-pH showed no evidence of postoperative pathologic GER. The overall number of GER episodes was normal in both the upright and recumbent position. This reduction was obtained because of the postoperative control of both the acid and nonacid reflux episodes. The Nissen fundoplication adequately controls both acid and nonacid GER after extended Heller myotomy. Further controls with MII-pH are warranted to check at a longer follow-up for the efficacy of this antireflux procedure in achalasic patients.

Total fundoplication does not obstruct the esophageal secondary peristalsis: investigation with pre- and postoperative 24-hour pH-multichannel intraluminal impedance.

AIM: To determine the impact of total fundoplication on the spontaneous esophageal clearance, known as secondary peristalsis. BACKGROUND: Although there is general agreement that total fundoplication is not an obstacle to bolus swallowing (primary peristalsis), whether it is an obstacle to spontaneous esophageal clearance (secondary peristalsis) is still not clear. Based on 24-hour monitoring, multichannel intraluminal impedance was used to calculate the time of spontaneous bolus clearance (BCT). METHODS: Mean BCT was prospectively calculated in 15 consecutive patients before and after total fundoplication. BCT was calculated in seconds including all the gastroesophageal reflux episodes, whereas bolus swallows (solid meals and liquid swallows) were excluded from the analysis. RESULTS: BCT was extrapolated from 1,057 episodes in the 623 h of study. Overall, BCT did not change after surgery (13.6 +/- 4 vs. 15.2 +/- 10 s; p = nonsignificant) and in the upright (12.2 +/- 3 vs. 16.5 +/- 7 s; p = nonsignificant) and recumbent position (22.9 +/- 9 vs. 23.0 +/- 9 s; p = nonsignificant). CONCLUSIONS: In this study total fundoplication did not affect the BCT by combined 24-hour ph monitoring and multichannel intraluminal impedance.

Mayer-Rokitansky-Küster-Hauser syndrome presenting as vaginal atresia: report of two cases.

Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome) is characterized by Müllerian duct structures agenesis: the vagina atresia is the commonest variant. There can be some anomalies associated, such as renal, skeletal, spine malformations and others. Patients with MRKH can show different presentation from newborn period to adolescence. We report our experience in treatment of the vaginal atresia presenting in two young girls as a sign of MRKH syndrome.

Development and validation of a bioanalytical method for quantification of LNA-i-miR-221, a 13-mer oligonucleotide, in rat plasma using LC-MS/MS.

LNA-i-miR-221, a 13-mer oligonucleotide, is a new miR-221 inhibitor that could be used as a novel drug for multiple myeloma. Herein, an ion-pair reversed phase liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantification of LNA-i-miR-221 in rat plasma. Plasma samples were prepared with an initial phenol/chloroform/isoamyl alcohol liquid-liquid extraction followed by a solid phase extraction. Chromatographic separation was performed with a gradient system on a HALO C18 column using hexafluoro-2-propanol/triethylamine buffer and methanol as mobile phase at a flow rate of 0.4 mL/min. Under these conditions LNA-i-miR-221 and the analogue internal standard are co-eluted at 1.2 min. The detection was carried out in multiple reaction monitoring (MRM) mode using a negative electrospray ionization (ESI) interface. The assay showed a good linearity within the calibration range 10-10000 ng/mL. The precision, accuracy, and recovery values were found to be <15% (<20% at LLOQ), 100 ±â€¯15%, and 97.6-103.7%, respectively. This method was successfully applied to measure the concentrations of LNA-i-miR-221 in plasma samples following the intravenous administration during a 4-week toxicity study in rats.

MiR-29b antagonizes the pro-inflammatory tumor-promoting activity of multiple myeloma-educated dendritic cells.

Dendritic cells (DCs) have a key role in regulating tumor immunity, tumor cell growth and drug resistance. We hypothesized that multiple myeloma (MM) cells might recruit and reprogram DCs to a tumor-permissive phenotype by changes within their microRNA (miRNA) network. By analyzing six different miRNA-profiling data sets, miR-29b was identified as the only miRNA upregulated in normal mature DCs and significantly downregulated in tumor-associated DCs. This finding was validated in primary DCs co-cultured in vitro with MM cell lines and in primary bone marrow DCs from MM patients. In DCs co-cultured with MM cells, enforced expression of miR-29b counteracted pro-inflammatory pathways, including signal transducer and activator of transcription 3 and nuclear factor-κB, and cytokine/chemokine signaling networks, which correlated with patients' adverse prognosis and development of bone disease. Moreover, miR-29b downregulated interleukin-23 in vitro and in the SCID-synth-hu in vivo model, and antagonized a Th17 inflammatory response. All together, these effects translated into strong anti-proliferative activity and reduction of genomic instability of MM cells. Our study demonstrates that MM reprograms the DCs functional phenotype by downregulating miR-29b whose reconstitution impairs DCs ability to sustain MM cell growth and survival. These results underscore miR-29b as an innovative and attractive candidate for miRNA-based immune therapy of MM.