Postbiotics produced at laboratory and industrial level as potential functional food ingredients with the capacity to protect mice against Salmonella infection.

AIM: To determine the protective capacity against Salmonella infection in mice of the cell-free fraction (postbiotic) of fermented milk, produced at laboratory and industrial level. METHODS AND RESULTS: The proteolytic activity (PA) of 5 commercial cultures and 11 autochthonous Lactobacillus strains was evaluated. The DSM-100H culture displayed the highest PA and it was selected for further studies. The capacity of the postbiotics produced by pH-controlled fermentation to stimulate the production of secretory IgA in faeces and to protect mice against Salmonella infection was evaluated. A significant increase in secretory IgA in faeces of mice fed 14 days the postbiotic obtained at the laboratory (F36) was detected compared to control animals. A significantly higher survival was observed in mice fed the F36 and the FiSD (industrial product) compared to controls. CONCLUSION: The postbiotics obtained showed immunomodulatory and protective capacity against Salmonella infection in mice. SIGNIFICANCE AND IMPACT OF THE STUDY: The pH-controlled milk fermentation by the proteolytic DSM-100H culture could be a suitable strategy to obtain a food ingredient to be added to a given food matrix, not adequate to host viable cells of probiotics, to confer it enhanced functionality and thus expand the functional food market.

Increased aortic stiffness index in patients with type 1 diabetes without cardiovascular disease compared to controls.

PURPOSE: Increased arterial stiffness is an early sign of endothelial dysfunction. Nevertheless, measures of the elastic properties of the aortic root in patients with type 1 diabetes are still lacking. The aim of this study was to compare aortic root stiffness index in type 1 diabetes and healthy controls. METHODS: Ninety-three patients with type 1 diabetes without cardiovascular diseases were recruited and compared to 33 healthy controls. Aortic root elastic properties were estimated by measuring the systolic and diastolic diameters on M-mode acquisition. RESULTS: None of the subjects showed alterations of either systolic or diastolic echocardiographic parameters. Patients with type 1 diabetes had a very low prevalence of chronic complications and their metabolic control was good. Significantly increased aortic stiffness index was found in type 1 diabetes compared to controls, and the same different pattern was found in men and women. The presence of type 1 diabetes and increased pulse pressure was significantly associated with aortic stiffness index in a multivariate linear analysis. CONCLUSION: This study strongly suggests that patients with type 1 diabetes develop aortic root stiffness in the absence of cardiovascular diseases. This alteration may be part of a more generalized arterial dysfunction in type 1 diabetes.

Role of transanal irrigation in the treatment of anterior resection syndrome.

BACKGROUND: Transanal irrigation(TAI) has been reported to be an inexpensive and effective treatment for low anterior resection syndrome(LARS). The aim of the present prospective study was to evaluate the use of TAI in patients with significant LARS symptoms at a single medical center. METHODS: Patients who had low anterior resection for rectal cancer between April 2015 and May 2016 at the Careggi University Hospital were assessed for LARS using the LARS and the Memorial Sloan-Kettering Cancer Center Bowel Function Instrument (MSKCC BFI) questionnaires 30-40 days after  surgery or ileostomy closure (if this was done). Quality of life was evaluated using a visual analog scale and the Short Form-36 Health Survey. All patients with LARS score of 30 or higher were included (early LARS) as were all patients with a LARS score of 30 or higher referred 6 months or longer after surgery performed elsewhere (chronic LARS) in the same study period. Study participants were trained to perform TAI using the Peristeen™ System for 6 months, followed by 3 months of enema therapy following a similar protocol. RESULTS: Thirty-three patients were enrolled in the study. Six patients stopped the treatment. The 27 patients (19 early LARS and 8 chronic LARS) who completed the study had a significant decrease in the number of median daily bowel movements [baseline 7 (range 0-14); 6 months 1 (range 0-4); 9 months 4 (range 0-13)]. The median LARS Score fell from 35.1 (range 30-42) (baseline) to 12.2 (range 0-21) after 6 months (p < 0.0001) and then rose to 27 (range 5-39) after 3 months of enema therapy. There was no difference in LARS score decrease at 6 months between the patients with early and chronic LARS (22.5 and 23.9 respectively; p=0.7) and there were no predictors of score decrease. Four components of the SF-36 significantly improved during the TAI period. The MSKCC BFI score significantly improved in several domains. Twenty-three patients (85%) asked to continue the treatment with TAI after the study ended. CONCLUSIONS: TAI appears to be an effective treatment for LARS and results in a marked improvement of continence and quality of life.  Patients may be assessed and treated for LARS early after surgery since the treatment benefit is similar to that observed in patients with LARS diagnosed  6 months or longer after surgery. The potential rehabilitative role of TAI for LARS is promising and should be further investigated.

TPF plus cetuximab induction chemotherapy followed by biochemoradiation with weekly cetuximab plus weekly cisplatin or carboplatin: a randomized phase II EORTC trial.

BACKGROUND: Our aim was to test the safety of cetuximab added to chemoradiation with either cisplatin or carboplatin after prior induction chemotherapy. METHODS: Patients with stage III/IV unresectable, squamous cell carcinoma of the head and neck received up to four cycles of TPF-E (cisplatin and docetaxel 75 mg/m2 on day 1 followed by 5-FU 750 mg/m2/day as a continuous infusion on days 1-5 plus cetuximab at a loading dose of 400 mg/m2 followed by a weekly dose of 250 mg/m2), with prophylactic antibiotics but no growth factors. Patients not progressing after four cycles of TPF-E were randomly assigned to radiotherapy (70 Gy over 7 weeks in 2 Gy fractions) and weekly cetuximab with either weekly cisplatin 40 mg/m2 or carboplatin, AUC of 1.5 mg/ml/min. Primary endpoint was feasibility. RESULTS: Forty-seven patients were recruited. One patient did not start TPF (hypersensitivity reaction during the cetuximab loading dose). Induction TPF-E was discontinued in 12 patients due to toxicity (6 patients), medical decision (2), death (1), patient refusal (1), protocol violation (1), co-morbidity (1). Three further patients were not randomized [progressive disease (1), protocol violation (1), toxicity and co-morbidity (1)]. Of particular interest are three patients who suffered from bowel perforation, one patient who died as results of pneumonia and septic shock, and a second patient who was found dead at home 12 days after starting TPF-E (cause of death unknown). Weekly cisplatin and carboplatin was stopped early in seven and four patients, respectively. Radiotherapy was stopped in two patients with cisplatin and interrupted in one patient with cisplatin and four patients with carboplatin. CONCLUSIONS: The addition of cetuximab to full dose TPF induction chemotherapy led to unacceptable complications and premature closing of the study. Only 34 out of 46 patients completed four cycles of TPF-E and only 30 started biochemoradiation.

A randomized, double-blind, placebo-controlled, multicenter study of a ginger extract in the management of chemotherapy-induced nausea and vomiting (CINV) in patients receiving high-dose cisplatin.

BACKGROUND: The activity of ginger in the management of chemotherapy-induced nausea and vomiting (CINV) has been suggested, but design inadequacies, heterogeneity of the population, small numbers and poor quality of tested products limit the possibility to offer generalizable results. PATIENTS AND METHODS: We conducted a randomized, double-blind, placebo-controlled, multicenter study in patients planned to receive ≥2 chemotherapy cycles with high dose (>50 mg/m2) cisplatin. Patients received ginger 160 mg/day (with standardized dose of bioactive compounds) or placebo in addition to the standard antiemetic prophylaxis for CINV, starting from the day after cisplatin administration. CINV was assessed through daily visual-analogue scale and Functional Living Index Emesis questionnaires. The main objective was protection from delayed nausea; secondary end points included intercycle nausea and nausea anticipatory symptoms. RESULTS: In total, 121 patients received ginger and 123 placebo. Lung (49%) and head and neck cancer (HNC; 35%) were the most represented tumors. No differences were reported in terms of safety profile or compliance. The incidence of delayed, intercycle and anticipatory nausea did not differ between the two arms in the first cycle and second cycle. A benefit of ginger over placebo in Functional Living Index Emesis nausea score differences (day 6-day 1) was identified for females (P = 0.048) and HNC patients (P = 0.038). CONCLUSIONS: In patients treated with high-dose cisplatin, the daily addition of ginger, even if safe, did not result in a protective effect on CINV. The favorable effect observed on nausea in subgroups at particular risk of nausea (females; HNC) deserves specific investigation.

Involvement of cell surface TG2 in the aggregation of K562 cells triggered by gluten.

Gluten-induced aggregation of K562 cells represents an in vitro model reproducing the early steps occurring in the small bowel of celiac patients exposed to gliadin. Despite the clear involvement of TG2 in the activation of the antigen-presenting cells, it is not yet clear in which compartment it occurs. Herein we study the calcium-dependent aggregation of these cells, using either cell-permeable or cell-impermeable TG2 inhibitors. Gluten induces efficient aggregation when calcium is absent in the extracellular environment, while TG2 inhibitors do not restore the full aggregating potential of gluten in the presence of calcium. These findings suggest that TG2 activity is not essential in the cellular aggregation mechanism. We demonstrate that gluten contacts the cells and provokes their aggregation through a mechanism involving the A-gliadin peptide 31-43. This peptide also activates the cell surface associated extracellular TG2 in the absence of calcium. Using a bioinformatics approach, we identify the possible docking sites of this peptide on the open and closed TG2 structures. Peptide docks with the closed TG2 structure near to the GTP/GDP site, by establishing molecular interactions with the same amino acids involved in stabilization of GTP binding. We suggest that it may occur through the displacement of GTP, switching the TG2 structure from the closed to the active open conformation. Furthermore, docking analysis shows peptide binding with the ß-sandwich domain of the closed TG2 structure, suggesting that this region could be responsible for the different aggregating effects of gluten shown in the presence or absence of calcium. We deduce from these data a possible mechanism of action by which gluten makes contact with the cell surface, which could have possible implications in the celiac disease onset.

Evidence of left atrial remodeling and left ventricular diastolic dysfunction in type 2 diabetes mellitus with preserved systolic function.

BACKGROUND AND AIMS: Prognosis of type 2 diabetes is associated with the occurrence of cardiovascular diseases. Left atrial (LA) size is a predictor of outcome in several diseases, including diabetes. Long duration of diabetes is an established risk factor of poor prognosis. No data are available on the relationship between LA size and duration of diabetes. The present study was aimed to investigate the relationship between LA volume index (LAVI) and the duration of diabetes to test the hypothesis that LA volume will increase as a function of diabetes duration. METHODS AND RESULTS: Forty-four male patients with newly diagnosed and 172 male patients with established type 2 diabetes were recruited for this cross-sectional study. All patients were evaluated with a transthoracic echocardiographic Doppler. About 28.2% of patients had increased LAVI. Indices of both diastolic and systolic function were significantly lower in patients with larger left atrium. The values of LAVI increased across classes of duration of diabetes. In multivariable analysis, longer duration was a predictor of LAVI ≥34 ml/m2 (odds ratio 1.65, 95% CI 1.11-2.46, p = 0.014) after adjusting for age, hemoglobin A1c, hypertension, microvascular complication status, and relevant echocardiographic parameters of systolic and diastolic function. CONCLUSIONS: These results indicate that duration of diabetes is strongly and positively associated with larger LAVI in type 2 diabetic men with preserved systolic function. Future studies are needed to better elucidate the biological mechanisms underlying linking type 2 diabetes with abnormally increased LAVI in subjects with type 2 diabetes.

Hyperuricemia is associated with an increased prevalence of atrial fibrillation in hospitalized patients with type 2 diabetes.

PURPOSE: Hyperuricemia/gout and atrial fibrillation (AF) are two pathological conditions that are highly prevalent in type 2 diabetes and share multiple cardiovascular risk factors. However, the relationship between elevated levels of serum uric acid and risk of AF in type 2 diabetes is currently poorly known. METHODS: We studied a hospital-based sample of 842 (male/female = 463/379) patients with type 2 diabetes discharged from our Division of Endocrinology during 2007-2011. Hyperuricemia was defined as a serum uric acid level >7 mg/dl for men and >6 mg/dl for women or allopurinol use. The diagnosis of AF was confirmed in affected participants on the basis of ECGs and medical history by experienced cardiologists. RESULTS: Overall, 243 (28.9 %) patients had hyperuricemia and 91 (10.8 %) patients had persistent or permanent AF. Compared with those with normal serum uric acid levels, patients with hyperuricemia had a remarkably greater prevalence of AF (20.6 vs. 7.1 %; p < 0.001). Hyperuricemia was significantly associated with an increased risk of prevalent AF (odds ratio 3.41, 95 % CI 2.19-5.32; p < 0.001). Adjustments for age, sex, smoking, hemoglobin A1c, hypertension status, chronic kidney disease, chronic obstructive pulmonary disease and previous histories of hyperthyroidism, ischemic heart disease and valvular heart diseases did not weaken this association (adjusted-odds ratio 6.27, 95 % CI 1.82-21.5; p < 0.01). CONCLUSIONS: These results indicate that hyperuricemia is associated with an increased prevalence of AF in hospitalized patients with type 2 diabetes, independently of multiple risk factors and potential confounders.

Plasmin and coagulant activities in a minicurd model system: Study of technological parameters.

The effect of scalding temperature of the curd, the inclusion of a washing step, and the pH at whey drainage on plasmin and coagulant activities were assessed in a minicurd model of young hard cooked cheese. The variables were tested as follows: draining pH was assayed at 3 levels (4.6, 5.6, and 6.4), curd scalding temperature was tested at 50 and 56°C, and washing of the curd was examined at 2 levels (no washing step, and the replacement of the whey by water). Increase in pH at whey drainage and washing of the curd had a positive effect on plasmin activity, which was also evidenced by compatible changes in soluble peptide profiles. No effect of increased cooking temperature was found on plasmin activity. Plasminogen activation was not verified in any treatment. As for coagulant, lower pH values at whey drainage and a decrease in curd cooking temperature increased its activity; washing of the curd showed no influence on coagulant residual activity. These results were consistent with proteolysis described by peptide profiles, electrophoresis, and soluble nitrogen fractions.

A practical approach for the detection of DNA nanostructures in single live human cells by fluorescence microscopy.

In the last decade, in vivo studies have revealed that even subtle differences in size, concentration of components, cell cycle stage, make the cells in a population respond differently to the same stimulus. In order to characterize such complexity of behavior and shed more light on the functioning and communication amongst cells, researchers are developing strategies to study single live cells in a population. In this paper, we describe the methods to design and prepare DNA-based fluorescent tetrahedral nanostructures, to deliver them to live cells and characterize such cells with epifluorescence microscopy. We report that HeLa cells internalize these nanostructures spontaneously with a higher efficiency with respect to single-stranded or double-stranded oligonucleotides. Our findings suggest that DNA tetrahedra could serve as a platform for the realization of a series of multifunctional intracellular biosensors for the analysis of single live cells.

Growth, survival, and peptidolytic activity of Lactobacillus plantarum I91 in a hard-cheese model.

In this work, we studied the growth, survival, and peptidolytic activity of Lactobacillus plantarum I91 in a hard-cheese model consisting of a sterile extract of Reggianito cheese. To assess the influence of the primary starter and initial proteolysis level on these parameters, we prepared the extracts with cheeses that were produced using 2 different starter strains of Lactobacillus helveticus 138 or 209 (Lh138 or Lh209) at 3 ripening times: 3, 90, and 180 d. The experimental extracts were inoculated with Lb. plantarum I91; the control extracts were not inoculated and the blank extracts were heat-treated to inactivate enzymes and were not inoculated. All extracts were incubated at 34°C for 21 d, and then the pH, microbiological counts, and proteolysis profiles were determined. The basal proteolysis profiles in the extracts of young cheeses made with either strain tested were similar, but many differences between the proteolysis profiles of the extracts of the Lh138 and Lh209 cheeses were found when riper cheeses were used. The pH values in the blank and control extracts did not change, and no microbial growth was detected. In contrast, the pH value in experimental extracts decreased, and this decrease was more pronounced in extracts obtained from either of the young cheeses and from the Lh209 cheese at any stage of ripening. Lactobacillus plantarum I91 grew up to 8 log during the first days of incubation in all of the extracts, but then the number of viable cells decreased, the extent of which depended on the starter strain and the age of the cheese used for the extract. The decrease in the counts of Lb. plantarum I91 was observed mainly in the extracts in which the pH had diminished the most. In addition, the extracts that best supported the viability of Lb. plantarum I91 during incubation had the highest free amino acids content. The effect of Lb. plantarum I91 on the proteolysis profile of the extracts was marginal. Significant changes in the content of free amino acids suggested that the catabolism of free amino acids by Lb. plantarum I91 prevailed in a weakly proteolyzed medium, whereas the release of amino acids due to peptidolysis overcame their catabolism in a medium with high levels of free amino acids. Lactobacillus plantarum I91 was able to use energy sources other than lactose to support its growth because equivalent numbers of cells were observed in extracts containing residual amounts of lactose and in lactose-depleted extracts. The contribution of Lb. plantarum I91 to hard-cooked cheese peptidolysis was negligible compared with that of the starter strain; however, its ability to transform amino acids is a promising feature of this strain.

Tumor stage, human papillomavirus and smoking status affect the survival of patients with oropharyngeal cancer: an Italian validation study.

BACKGROUND: Tumor human papillomavirus (HPV) status strongly affects overall survival (OS) of oropharyngeal cancer (OPC) patients. Recently, three groups with different outcomes were identified based on HPV status, smoking history and tumor stage. Our objective was to validate this model using a single-institutional retrospective database. PATIENTS AND METHODS: Patients (n=120) diagnosed with OPC at our institution, treated with concomitant cisplatin plus radiotherapy (RT) (n=64), induction chemotherapy followed by concomitant chemoradiation (n=39) or RT alone (n=17), were stratified in three groups with respect to the risk of death (low 26, intermediate 46 and high 49 patients) according to tumor p16 expression as surrogate of HPV status, pack-years of tobacco smoking and nodal/tumor stage. Group-stratified Kaplan-Meier OS curves were estimated and compared using the log-rank test. RESULTS: The 2-year OS estimates were 100%, 86% and 70%, respectively. The difference between the survival curves was statistically significant (P=0.009). The Harrell's concordance index was 0.70. The calibration plot showed a good concordance between our results and those observed in the original study. CONCLUSIONS: This study validates the risk grouping previously identified. Risk-driven clinical decision making and trial designs will help in better defining the most appropriate treatment in OPC patients.

Laparoscopic adhesiolysis: consensus conference guidelines.

AIM: Laparoscopic adhesiolysis has been demonstrated to be technically feasible in small bowel obstruction and carries advantages in terms of post-surgical course. The increasing dissemination of laparoscopic surgery in the emergency setting and the lack of concrete evidence in the literature have called for a consensus conference to draw recommendations for clinical practice. METHODS: A literature search was used to outline the evidence, and a consensus conference was held between experts in the field. A survey of international experts added expertise to the debate. A public jury of surgeons discussed and validated the statements, and the entire process was reviewed by three external experts. RESULTS: Recommendations concern the diagnostic evaluation, the timing of the operation, the selection of patients, the induction of the pneumoperitoneum, the removal of the cause of obstructions, the criteria for conversion, the use of adhesion-preventing agents, the need for high-technology dissection instruments and behaviour in the case of misdiagnosed hernia or the need for bowel resection. CONCLUSION: Evidence of this kind of surgery is scanty because of the absence of randomized controlled trials. Nevertheless laparoscopic skills in emergency are widespread. The recommendations given with the consensus process might be a useful tool in the hands of surgeons.

Docetaxel, cisplatin and 5-fluorouracil-based induction chemotherapy followed by intensity-modulated radiotherapy concurrent with cisplatin in locally advanced EBV-related nasopharyngeal cancer.

BACKGROUND: This monocentric study evaluates the activity and tolerability of docetaxel (Taxotere), cisplatin and 5-fluorouracil (5-FU) (TPF) induction chemotherapy followed by intensity-modulated radiotherapy (IMRT) concurrent with high-dose cisplatin in Epstein-Barr virus -related locally advanced undifferentiated nasopharyngeal cancer. PATIENTS AND METHODS: We retrospectively reviewed the records of patients who received induction docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) on day 1, and 5-FU 750 mg/m(2)/day (96-h continuous infusion). Following induction, patients received full doses of IMRT concurrently with cisplatin 100 mg/m(2) every 21 days for three cycles. RESULTS: Thirty patients received three TPF cycles (median). Induction was well tolerated; the main toxicity was neutropenia (33%, grade 3-4). During chemoradiotherapy, neutropenia (40%) and mucositis (43%) were the most frequent grade 3-4 adverse events. Mean dose of IMRT was 68.8 Gy. Worst late toxicity was xerostomia. Complete response rate was 93%. At 35 months, two patients had locoregional recurrence, three had distant metastases, and one had both. Three-year progression-free survival and overall survival were 79% [95% confidence interval (CI) 64% to 94%] and 87% (95% CI 74%- to 100%), respectively. CONCLUSIONS: In this high-stage nonendemic cancer population, TPF followed by high-dose cisplatin IMRT was promising; this treatment approach deserves evaluation in randomized trials.

How to incorporate left atrial strain in the diagnostic algorithm of left ventricular diastolic dysfunction.

The combination of early trans-mitral inflow and mitral annular tissue Doppler velocities (E/e' ratio) is widely applied to noninvasively estimate left ventricular (LV) filling pressures. However, when E/e' is between 8 and 14 its accuracy decreases substantially. Left atrial (LA) deformation analysis by speckle tracking echocardiography was recently proposed as an alternative approach to estimate LV filling pressures, but its role when E/e' is between 8 and 14 has been under-investigated. We aimed to assess whether LA strain could help to identify elevated filling pressures in patients with E/e' between 8 and 14. Among consecutive non-selected patients who underwent a comprehensive echocardiographic evaluation, we enrolled those with E/e' ratio > 8 and ≤ 14. Exclusion criteria were: organic mitral valve disease or mitral surgery; presence of mitral regurgitation greater than moderate in severity; diseases associated with pre-capillary pulmonary hypertension; and undetectable systolic pulmonary artery pressure (PAP-S). Peak LA longitudinal (PALS) and contraction strain (PACS) values was obtained by averaging all segments, and by separately averaging segments measured in the 4-chamber and 2-chamber views. Seventy-six patients had E/e' > 8 and ≤ 14 and formed the study cohort. Mean age 69 ± 12 years, LV ejection fraction (LVEF) 54.5 ± 11.2%, mean E/e' 11.2 ± 1.9, PAP-S 33 ± 7 mmHg, PALS 31.6 ± 11.7%. PALS was significantly associated to PAP-S after adjustment for LVEF, E/e', septal LV longitudinal shortening velocity (s'), LA volume indexed (p = 0.002) and also for ASE/EACVI diastolic dysfunction classification (p = 0.0002). Furthermore, PALS but not ASE/EACVI diastolic dysfunction grading, resulted independently associated to New York Heart Association (NYHA) class (p = 0.0004). PALS is able to predict increased intra-cardiac pressure and NYHA class in patients characterized by E/e' between 8 and 14. Therefore, we propose that PALS might be incorporated in a simplified diagnostic algorithm based on E/e' classes.

Late toxicities burden in patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib.

PURPOSE: Radioactive-iodine (RAI)-resistant differentiated thyroid cancer (DTC) patients benefit from multi-kinase inhibitors (MKIs), such as lenvatinib. Incidence of treatment-related (TR) late toxicities has been not yet described. METHODS: From January 2015 to June 2019 we retrospectively reviewed clinical records of patients with RAI-resistant DTC treated with lenvatinib at Istituto Nazionale dei Tumori (Milan, Italy). New side effect of any grade, appeared after 12 months of lenvatinib, was defined as late adverse event (AE). Descriptive analyses were performed. Survival curves were estimated with Kaplan-Meier method and compared with log-rank test. RESULTS: Thirty-seven patients were included, 65% had ≥65 years and 68% were female. Thirty patients received lenvatinib for >12 months. Lenvatinib was started at ≤20 mg/daily in 59% of patients, 64% were ≥65 years. The frequency of late AEs was 80% and cardiovascular toxicity was the most common (57%). There was no difference in the incidence of late AEs between younger/older population (77% and 82%, respectively). Median lenvatinib treatment duration (TD) was 39.96 months (95% CI 21.64-NR): 39.96 months for patients <65 years (95% CI: 13.25-NR) and 37.53 months for those ≥65 years, respectively (95% CI: 15.85-NR). Median overall survival (OS) was 39.96 months (95% CI: 21.84-NR), no statistically differences in OS was observed between younger (<65 years) and older patients (≥65 years) (HR 1.013; 95% CI 0.963-1.065; p = 0.62). CONCLUSION: Late toxicity burden of lenvatinib is not negligible. Cardiovascular toxicity remains the principal side effect even after a prolonged lenvatinib exposition.

Two strains of nonstarter lactobacilli increased the production of flavor compounds in soft cheeses.

The contribution to flavor generation and secondary proteolysis of 2 strains of mesophilic lactobacilli isolated from cheese was studied. Miniature soft cheeses (200 g) were produced with or without the inclusion of a culture of Lactobacillus plantarum I91 or Lactobacillus casei I90 in the starter composed of Streptococcus thermophilus. During ripening, cheeses containing the added lactobacilli showed an increased content of total free amino acids, but this increase was only significant in cheeses with Lb. plantarum I91. In addition, free amino acid profiles were modified by selective increases of some amino acids, such as Asp, Ser, Arg, Leu, and Phe. Cheeses inoculated with Lb. plantarum I91 or Lb. casei I90 were also characterized by a significantly higher concentration of diacetyl, a key flavor compound, and an increased content of acetoin. Results suggest an increase in the catabolism of either citrate or aspartate, with the production of the derived aroma compounds. Overall, aspartate content increased in both lactobacilli-added cheeses, whereas citrate was more or less constant, suggesting that aspartate could be the source of increased diacetyl and acetoin. A triangle aroma test showed that the addition of the lactobacilli strains significantly changed the sensory attributes of cheeses. At least 11 of 12 panelists commented that the aroma of cheeses with adjuncts was more buttery than that of control cheeses, which is desirable in most soft cheeses. Both Lb. plantarum I91 and Lb. casei I90 performed well as adjunct cultures by influencing cheese aroma development and cheese proteolysis.

[Update on the laparoscopic adrenal surgery in the second decade of the century: "doubts no more?]. / Update sulla chirurgia laparoscopica del surrene nel secondo decennio del secolo: "doubts no more?"

Laparoscopic adrenal surgery has significantly improved during the last years. Thus at the moment it is possible to define such technique as the therapeutic "Gold Standard" option in the treatment of the adrenal tumors. However, some doubts are still remaining concerning the feasibility of laparoscopic adrenalectomy in case of malignant adrenal tumors, hyper-vascular tumors (pheochromocytoma) and indeterminate incidentaloma. This study aimed to review all the literature of the last three years (only article with abstracts) using the criteria of selection of the Cochrane Library, in order to find class I and class II-III studies which are able to surely or, respectively, probably respond to the various questions yet to be answered Two hundred and twelve papers have been selected. The class I studies stated the following evidences: laparoscopic treatment of pheochromocytoma is the Gold Standard too, independently from the dimension; the short term results of laparoscopic anterior and posterior approach are equivalent to those of the lateral one. Doubts still remain concerning the role of laparoscopy in the treatment of metastases, big pheochromocytomas, small size incidentalomas (risk of over-treatement). Nearly no respond has been given to others issues such as "the single port techniques" in laparoscopic adrenalectomy, the role of radiofrequency laparoscopic ablation of the adrenal tumor, the kind of treatment of stadium I and II adrenocortical carcinoma and big size (> 8 cm) tumors, the management of non-functioning incidentaloma of 4-6 cm, the role of the robot, and, finally, the approach of the bilateral tumors. We conclude that, despite many issues on the feasibility and safety of laparoscopy in the adrenal surgery have been definitely clarified, so that such technique has been declared the "Gold Standard" method in the treatment of the adrenal tumor, doubts still remain in some aspects of this method. However, since the researches in this field are proceeding with high evolution velocity, in the next future most of the questions that are still present should be definitively adressed.

Estimated peak systolic pulmonary artery pressure in young non-complicated patients with type 1 diabetes.

OBJECTIVE: Right ventricle and pulmonary artery pressure have always received less attention in type 1 diabetes than left ventricle. The aim of this study is to compare the right heart performance and the estimated peak systolic pulmonary artery pressure (EPSPAP) in young type 1 diabetes patients with healthy controls. PATIENTS AND METHODS: Subjects affected by type 1 diabetes without cardiovascular and respiratory diseases (n=93) and healthy controls (n=56) were evaluated with a comprehensive transthoracic echocardiography. The pulmonary peak systolic arterial pressure was calculated with an established formula based on pulmonary artery acceleration time. RESULTS: The left ventricle's function was found to be normal in all the subjects under study. The estimated peak systolic pulmonary artery pressure was significantly higher in patients with type 1 diabetes compared to the controls (38.5 ± 8.6 vs. 35.4 ± 6.7, p = 0.019). The highest value of EPSPAP was observed in smoking female patients with type 1 diabetes. Basal and mid cavity diameter of the right ventricle were higher in patients with type 1 diabetes. Factors associated with EPSPAP were sex, body mass index, mid cavity diameter and, with an inverse correlation, HDL-cholesterol. CONCLUSIONS: The present study suggests that young, uncomplicated patients with type 1 diabetes have a higher estimated peak systolic pulmonary artery pressure. Further studies are needed to define the mechanisms underlying this alteration and its clinical consequences.