Radio-iodine refractory thyroid cancer patients: a tailored follow-up based on clinicopathological features.

OBJECTIVE: To report the experience of a single center for the selection of radioiodine-refractory (RAIR) thyroid cancer patients (RAIR-TC) who needed tyrosine kinase inhibitor (TKIs) treatment. PATIENTS AND METHODS: We evaluated all features of 279 RAIR-TC patients both at the time of diagnosis and at the RAIR diagnosis. RESULTS: Ninety-nine patients received indication to TKIs (Group A), while 180 remained under active surveillance (Group B). Group A had greater tumor size, more aggressive histotype, more frequent macroscopic extrathyroidal extension, distant metastases, advanced AJCC stage, and higher ATA risk of recurrence. After RAIR diagnosis, 93.9% of Group A had progression of disease (PD) after which TKIs' therapy was started. The remaining 6.1% of patients had a so severe disease at the time of RAIR diagnosis that TKIs' therapy was immediately started. Among Group B, 42.7% had up to 5 PD, but the majority underwent local treatments. The mean time from RAIR diagnosis to the first PD was shorter in Group A, and the evidence of PD within 25 months from RAIR diagnosis was associated with the decision to start TKIs. CONCLUSIONS: According to our results, a more tailored follow-up should be applied to RAIR-TC patients. A too strict monitoring and too many imaging evaluations might be avoided in those with less-aggressive features and low rate of progression. Conversely, RAIR-TC with an advanced stage at diagnosis and a first PD occurring within 25 months from RAIR diagnosis would require a more stringent follow-up to avoid a late start of TKIs.

Long-term urological outcome of cloaca patients with multidisciplinary management.

PURPOSE: Urological management of Cloacal Malformation (CM) focuses on preserving renal function and continence. Study aim was to analyze urinary and intestinal outcomes in CM patients, considering the length of common channel (CC) and presence of occult spinal dysraphism (OSD). METHODS: Retrospective review of CM treated at our institution by a multidisciplinary team from 1999 to 2020. Patients with follow-up < 2.5 years were excluded. Length of CC, renal function, urinary and bowel outcomes, presence of associated anomalies (especially OSD) were evaluated. RESULTS: Twenty patients were included, median age at follow-up: 8 years (4-15). A long CC > 3 cm was described in 11 (55%). Chronic kidney disease was found in 3 patients. Urinary continence was achieved in 8/20 patients, dryness (with intermittent catheterization) in 9/20. Fecal continence was obtained in 3/20, cleanliness in 14 (under bowel regimen). OSD was present in 10 patients (higher prevalence in long-CC, 73%). Among OSD, 1 patient reached fecal continence, 7 were clean; 2 achieved urinary continence, while 6 were dry. CONCLUSIONS: Length of CC and OSD may affect urinary and fecal continence. An early counseling can improve outcome at long-term follow-up. Multidisciplinary management with patient centralization in high grade institutions is recommended to achieve better results.

The diurnal patterns of ruminal enzymatic activity and in vitro digestibility of starch, neutral detergent fiber, and protein.

The objective of this study was to determine whether diurnal patterns in starch, neutral detergent fiber (NDF) and protein digestibilities and amylolytic, fibrolytic, and proteolytic activities exist in dairy cows. Rumen fluid was collected from 4 ruminally cannulated Holstein dairy cows before the morning feeding and subsequently every 4 h for a 24-h period. Two of the cows were restricted from feed for 8 h overnight, and the other 2 continued to receive their feed ad libitum, to isolate and quantify the effects of changes in feeding behavior at night. After 2 runs the cows were crossed over between night feeding treatments. Rumen fluid was analyzed for enzymatic activity and in vitro starch, NDF, and nitrogen digestibility. Circadian rhythm analyses of enzymatic activity and in vitro digestibility were conducted by fitting the linear form of a cosine function with a 24-h period. Patterns were observed in activity for amylase, lichenase, endoglucanase, and xylanase, with the highest activities observed at the time points subsequent to milking and feed delivery. Protease activity was unaffected by either feeding treatment or possible feeding behavior. When fitted to a cosine function, all the parameters tested followed a daily pattern that was sensitive to the overnight availability of feed, although the parameters responded differently to the feeding treatment. The patterns displayed by in vitro digestibility results of starch, NDF, and nitrogen, across the various fluid collection time points, were highly variable. The time at peak (acrophase) observed in the enzymatic analysis did not correspond to those observed in the in vitro analysis. These results suggest that different interpretations should be given to enzymatic activities and in vitro digestibility values, and the time of rumen fluid collection relative to feeding time should be considered and reported when rumen fluid is used for research or commercial purposes. Maximum digestibility appears in fact to be reached around 4 to 5 h after the main ration delivery for NDF and starch and around ration delivery for protein.

Mathematical modelling of an intermittent anoxic/aerobic MBBR: Estimation of nitrification rates and energy savings.

This study aimed at modelling the performance of a novel MBBR configuration, named A/O-MBBR, comprised of a pre-anoxic reactor, with an HRT of 4.5 h, coupled with an intermittent anoxic/aerobic MBBR (HRT = 6.8 h). The lab-scale system was fed with municipal wastewater with an average influent Total Ammonia Nitrogen (TAN) and total COD (TCOD) concentrations of 46 mg of TAN-N L-1 and 310 mg TCOD L-1. During the whole experimental period, TAN removal efficiency was always higher than 96%; denitrification was also very effective, achieving nitrate and nitrite concentrations in the effluent both lower than 5 mg NOx-N L-1 on average. Moreover, TCOD average removal efficiency was equal to 85%. Modelling was performed to investigate the nitrification efficacy enhancement; to this aim, a biofilm model was developed, adopting the equations for mixed-culture biofilms and the Activated Model Sludge n°1 (ASM1) for the biological processes rates. The model allowed to determine the maximum uptake rate for autotrophic growth (µA was 2.5 d-1) and the semisaturation constant (KOA was 0.2 mg O2 L-1), suggesting that the nitrification process was 3-fold faster than average and very effective at low oxygen concentrations. The model estimated that about 85% of TAN was removed by the biofilm and only the remaining part by suspended biomass in the bulk liquid. Finally, it was assessed that the A/O-MBBR configuration allowed for a 45-60% savings of the energy requirement compared to a Benchmark WWTP layout.

Immediate versus staged revascularisation of non-culprit arteries in patients with acute coronary syndrome: a systematic review and meta-analysis.

Although there is robust evidence that revascularisation of non-culprit vessels should be pursued in patients presenting with an acute coronary syndrome (ACS) and multivessel coronary artery disease (MVD), the optimal timing of complete revascularisation remains disputed. In this systematic review and meta-analysis our results suggest that outcomes are comparable for immediate and staged complete revascularisation in patients with ACS and MVD. However, evidence from randomised controlled trials remains scarce and cautious interpretation of these results is recommended. More non-biased evidence is necessary to aid future decision making on the optimal timing of complete revascularisation.

ADM1-based mechanistic model for the role of trace elements in anaerobic digestion processes.

An original mechanistic model able to describe the fate of trace elements (TE) in anaerobic digestion systems has been synthetized from mass balance equations. The model takes into account the main biochemical and physico-chemical processes affecting TE bioavailability and it is aimed at evaluating the effect that the combination of such processes exerts on the system performance. Five main modules have been introduced: biochemistry, physico-chemistry, sorption, complexation and precipitation. The model is based on mass conservation principles and is formulated as a set of ordinary differential equations for the soluble and particulate components constituting the system. Model applications of two illustrative cases are provided. The first case is based on experimental results and examines the effect of TE depletion in an AD process of food waste (FW). The second case shows the effects of different metal supplements on methane production and biogas composition. The simulation results confirm that the model can fairly be used to predict the effect of TE dynamics and bioavailability, by considering biological, chemical and physicochemical processes in AD environments.

The Italian version of rheumatoid arthritis pain scale (IT-RAPS): psychometric properties on community and clinical samples.

This paper describes the validation process of the Italian version of the Rheumatoid Arthritis Pain Scale (ITRAPS), describing its translation and adaptation to Italian culture. The cultural adaptation and validation were based on data from a sample of people affected by rheumatoid arthritis (RA). The process required a forward and backward translation of the original language, reviewed by an expert panel. The adapted version of the RAPS was then tested on a community and clinical sample, in order to test its psychometric properties. The IT-RAPS was submitted to 122 people affected by RA. The data was analyzed using Cronbach's coefficient alpha and the Pearson product-moment correlation coefficients. The IT-RAPS showed an internal consistency reliability coefficient of 0.96. This is the first study reporting the validation and cross-cultural adaptation of the RAPS in Italian. The study's findings provided support for the IT-RAPS as a reliable and valid measurement of multidimensional pain in RA patients.

Continuum and discrete approach in modeling biofilm development and structure: a review.

The scientific community has recognized that almost 99% of the microbial life on earth is represented by biofilms. Considering the impacts of their sessile lifestyle on both natural and human activities, extensive experimental activity has been carried out to understand how biofilms grow and interact with the environment. Many mathematical models have also been developed to simulate and elucidate the main processes characterizing the biofilm growth. Two main mathematical approaches for biomass representation can be distinguished: continuum and discrete. This review is aimed at exploring the main characteristics of each approach. Continuum models can simulate the biofilm processes in a quantitative and deterministic way. However, they require a multidimensional formulation to take into account the biofilm spatial heterogeneity, which makes the models quite complicated, requiring significant computational effort. Discrete models are more recent and can represent the typical multidimensional structural heterogeneity of biofilm reflecting the experimental expectations, but they generate computational results including elements of randomness and introduce stochastic effects into the solutions.

The inclusion of fresh forage in the lactating buffalo diet affects fatty acid and sensory profile of mozzarella cheese.

The aim of this study was to determine the effect of inclusion of fresh forage in diet for lactating buffalo on properties of mozzarella cheese under intensive farming conditions. Thirty-two buffalo cows were equally allotted into 2 groups fed diets with (fresh group, FRS) or without (control group, CTL) fresh sorghum. The study consisted of 2 trials. In the first one, animals from group FRS were fed a diet containing 10 kg of fresh sorghum (10-FRS diet) that was doubled to 20 kg (20-FRS diet) in the second trial. All diets were isonitrogenous and isoenergetic, and fresh forage accounted for 13.4 and 26.5 of dietary dry matter, respectively, for the 10-FRS and 20-FRS diet. In each trial, milk from the 2 groups was used to produce 3 batches/diet of Mozzarella di Bufala Campana Protected Designation of Origin cheese. Milk yield and composition were not influenced by dietary treatment. The use of 10-FRS diet did not affect any properties of mozzarella. As the inclusion rate of fresh sorghum doubled to 20 kg, an increment of unsaturated fatty acid percentages and a lowering of short-chain and saturated fatty acids were observed. Moreover, the sensory characteristics of mozzarella were modified, although no effects were observed on consumer acceptance. We conclude that the use of green fodder can represent a low-cost feeding strategy to improve the healthiness of buffalo mozzarella under intensive farming conditions with no detrimental effect on consumer blind acceptance.

Salivary α-amylase as a marker of stress reduction in individuals with intellectual disability and autism in response to occupational and music therapy.

BACKGROUND: Although the benefits of a range of disability-centric therapies have been well studied, little remains known about how they work, let alone how to monitor these benefits in a precise and reliable way. METHODS: Here, in two independent studies, we examine how sessions consisting of occupational or music therapy, both widely recognised for their effectiveness, modulate levels of salivary α-amylase (sAA), a now time- and cost-efficient marker of stress, in individuals with intellectual disability and autism spectrum disorder. Pre-session and post-session levels of sAA were compared in both groups in response to therapy and control sessions. RESULTS: In comparison to control sessions, occupational therapy significantly dampened rises in sAA levels while music therapy significantly decreased baseline sAA levels, highlighting the ability of both types of therapy to reduce stress and by proxy contribute to enhancing overall well-being. CONCLUSIONS: Not only do these results confirm the stress-reducing nature of two types of multisensory therapy, but they support the use of sAA as a potential tool for evaluating stress levels in individuals with intellectual disability and autism spectrum disorder, providing an important physiological lens that may guide strategies in clinical and non-clinical care for individuals with disabilities.

Sensitivity analysis for an elemental sulfur-based two-step denitrification model.

A local sensitivity analysis was performed for a chemically synthesized elemental sulfur (S0)-based two-step denitrification model, accounting for nitrite (NO2 -) accumulation, biomass growth and S0 hydrolysis. The sensitivity analysis was aimed at verifying the model stability, understanding the model structure and individuating the model parameters to be further optimized. The mass specific area of the sulfur particles (a*) and hydrolysis kinetic constant (k1) were identified as the dominant parameters on the model outputs, i.e. nitrate (NO3 -), NO2 - and sulfate (SO4 2-) concentrations, confirming that the microbially catalyzed S0 hydrolysis is the rate-limiting step during S0-driven denitrification. Additionally, the maximum growth rates of the denitrifying biomass on NO3 - and NO2 - were detected as the most sensitive kinetic parameters.

Enteric glia: A new player in inflammatory bowel diseases.

In addition to the well-known involvement of macrophages and neutrophils, other cell types have been recently reported to substantially contribute to the onset and progression of inflammatory bowel diseases (IBD). Enteric glial cells (EGC) are the equivalent cell type of astrocyte in the central nervous system (CNS) and share with them many neurotrophic and neuro-immunomodulatory properties. This short review highlights the role of EGC in IBD, describing the role played by these cells in the maintenance of gut homeostasis, and their modulation of enteric neuronal activities. In pathological conditions, EGC have been reported to trigger and support bowel inflammation through the specific over-secretion of S100B protein, a pivotal neurotrophic factor able to induce chronic inflammatory changes in gut mucosa. New pharmacological tools that may improve the current therapeutic strategies for inflammatory bowel diseases (IBD), lowering side effects (i.e. corticosteroids) and costs (i.e. anti-TNFα monoclonal antibodies) represent a very important challenge for gastroenterologists and pharmacologists. Novel drugs capable to modulate enteric glia reactivity, limiting the pro-inflammatory release of S100B, may thus represent a significant innovation in the field of pharmacological interventions for inflammatory bowel diseases.

Low-radiation environment affects the development of protection mechanisms in V79 cells.

Very little is known about the influence of environmental radiation on living matter. In principle, important information can be acquired by analysing possible differences between parallel biological systems, one in a reference-radiation environment (RRE) and the other in a low-radiation environment (LRE). We took advantage of the unique opportunity represented by the cell culture facilities at the Gran Sasso National Laboratories of the Istituto Nazionale di Fisica Nucleare, where environment dose rate reduction factors in the underground (LRE), with respect to the external laboratory (RRE), are as follows: 10(3) for neutrons, 10(7) for directly ionizing cosmic rays and 10 for total γ-rays. Chinese hamster V79 cells were cultured for 10 months in both RRE and LRE. At the end of this period, all the cultures were kept in RRE for another 6 months. Changes in the activities of antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPX) and spontaneous mutation frequency at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus were investigated. The results obtained suggest that environmental radiation might act as a trigger of defence mechanisms in V79 cells, specifically those in reference conditions, showing a higher degree of defence against endogenous damage as compared to cells grown in a very low-radiation environment. Our findings corroborate the hypothesis that environmental radiation contributes to the development of defence mechanisms in today living organisms/systems.

Phytotoxicity of citric acid and Tween® 80 for potential use as soil amendments in enhanced phytoremediation.

Enhanced phytoremediation adding biodegradable amendments like low molecular weight organic acids and surfactants is an interesting area of current research to overcome the limitation that represents low bioavailability of pollutants in soils. However, prior to their use in assisted phytoremediation, it is necessary to test if amendments per se exert any toxic effect to plants and to optimize their application mode. In this context, the present study assessed the effects of citric acid and Tween® 80 (polyethylene glycol sorbitan monooleate) on the development of alfalfa (Medicago sativa) plants, as influenced by their concentration and frequency of application, in order to evaluate the feasibility for their future use in enhanced phytoremediation of multi-contaminated soils. The results showed that citric acid negatively affected plant germination, while it did not have any significant effect on biomass or chlorophyll content. In turn, Tween® 80 did not affect plant germination and showed a trend to increase biomass, as well as it did not have any significant effect on chlorophyll levels. M. sativa appeared to tolerate citric acid and Tween® 80 at the tested concentrations, applied weekly. Consequently, citric acid and Tween® 80 could potentially be utilized to assist phytoremediation of contaminated soils vegetated with M. sativa.

Prognostic significance of AMPK activation in advanced stage colorectal cancer treated with chemotherapy plus bevacizumab.

BACKGROUND: AMP-activated protein kinase (AMPK) has a central role in cellular energy sensing and is activated in preclinical tumour models following anti-vascular endothelial growth factor (VEGF) therapy. The possible predictive or prognostic role of AMPK status in cancer patients treated with anti-VEGF drugs has not been investigated so far. METHODS: Expression of components of the AMPK pathway including phosphorylated AMPK (pAMPK), phosphorylated acetyl-Coa carboxylase (pACC) and liver kinase B1 (LKB1) was investigated by immunohistochemistry in 48 colorectal cancers treated with FOLFIRI plus bevacizumab. Correlation between pAMPK and pACC and associations between the AMPK pathway scores and clinico-pathological characteristics were assessed. Overall survival (OS) was estimated through Kaplan-Meier method, whereas hazard ratios were computed to identify prognostic factors. RESULTS: Fourteen patients (29.2%) were included in the pAMPK-negative group (score ≤5), whereas 34 patients (70.8%) were included in the pAMPK-positive group (score >5). The Spearman's coefficient for the correlation between pAMPK and pACC scores in primary tumour samples was 0.514 (P=0.0002). Low pAMPK levels were associated with worse OS (P-value 0.0002) but not with PFS, whereas low pACC levels were associated both with worse OS and PFS (P-value 0.0007 and 0.01, respectively). CONCLUSIONS: Our findings suggest that high tissue AMPK activation is a prognostic biomarker in this cohort of metastatic colorectal cancer patients.

Fluidized-bed denitrification for mine waters. Part I: low pH and temperature operation.

Mining often leads to nitrate and metal contamination of groundwater and water bodies. Denitrification of acidic water was investigated in two up-flow fluidized-bed reactors (FBR) and using batch assays. Bacterial communities were enriched on ethanol plus nitrate in the FBRs. Initially, the effects of temperature, low-pH and ethanol/nitrate on denitrification were revealed. Batch assays showed that pH 4.8 was inhibitory to denitrification, whereas FBR characteristics permitted denitrification even at feed pH of 2.5 and at 7-8 °C. Nitrate and ethanol were removed and the feed pH was neutralized, provided that ethanol was supplied in excess to nitrate. Subsequently, Fe(II) and Cu impact on denitrification was investigated within batch tests at pH 7. Iron supplementation up to 100 mg/L resulted in iron oxidation and soluble concentrations ranging from 0.4 to 1.6 mg/L that stimulated denitrification. On the contrary, 0.7 mg/L of soluble Cu significantly slowed denitrification down resulting in about 45 % of inhibition in the first 8 h. Polymerase chain reaction-denaturant gradient gel electrophoresis demonstrated the co-existence of different denitrifying microbial consortia in FBRs. Dechloromonas denitrificans and Hydrogenophaga caeni were present in both FBRs and mainly responsible for nitrate reduction.

Fatty acid and sensory profiles of Caciocavallo cheese as affected by management system.

The effect of season of the year associated with changes in feeding and management system (pasture-based vs. confinement) on milk and cheese fatty acid profile and on sensory properties of Caciocavallo cheese was evaluated on 3 mountain dairy farms. Each farm used a pasture-based feeding system from April to June and from September to October (PS), and a confinement system for the rest of the year (CS). As a consequence of grazing, PS milk showed higher percentages of C18:3, cis-9,trans-11 conjugated linoleic acid, and trans-11 C18:1, and a reduced percentage of C16:0. The fatty acid profile of cheese largely reflected that of the corresponding raw milk from which cheese was made. This led to a significant decrease of atherogenic index in cheeses produced from cows on pasture. Based on sensory analysis, cheese from animals kept on pasture was more yellow and had a lower intensity of butter and smoked odors than did CS cheese. In addition, grazing induced a lower intensity of bitter and a higher intensity of spicy flavors compared with cheese from CS animals. In regard to texture, pasture feeding resulted in higher intensity of friability and graininess. All cheeses performed well in consumer tests; the panel found all samples more than acceptable for overall liking, and for liking according to appearance, taste/flavor, and texture. Overall liking of Caciocavallo cheese, as assessed by slope analysis, was affected primarily by taste/flavor (raw slope k=0.88) and texture (k=0.97), whereas appearance had a lesser effect (k=0.72). The acidic and sensory profiles of cheese were well discriminated, with healthier cheeses produced by grazing cows. Therefore, wider use of pasture should be promoted to accentuate this favorable feature. Based on the specific nutritional and sensory characteristics of mountain Caciocavallo cheese, particularly that obtained from grazing animals, efforts should be made to indicate the quality of this cheese to the consumer and improve product recognition.

The effects of conjugated linoleic acid isomers cis-9,trans-11 and trans-10,cis-12 on in vitro bovine embryo production and cryopreservation.

Conjugated linoleic acid (CLA) isomers can affect the lipid profile and signaling of cells and thereby alter their function. A total of 5,700 bovine oocytes were used in a structured series of experiments to test the effects of CLA cis-9,trans-11 and CLA trans-10,cis-12 in vitro. In experiment 1, high doses of each CLA isomer during in vitro maturation (IVM) were compared with high or low doses during the entire in vitro culture (IVC) of parthenogenetic embryos. High doses of the CLA isomers ranged from 50 to 200 µM and low doses were 15 and 25 µM. In experiment 2, the low doses of each CLA isomer were tested during IVM/IVC on embryos produced by in vitro fertilization (IVF). Experiment 3 compared the effects of 15 µM doses of each CLA isomer during IVM or IVC of IVF embryos. In experiment 4, post-rewarming survival rates and blastomere counts were assessed for embryos supplemented with each CLA isomer during IVM or for 36 h before vitrification. In experiment 1, when either CLA isomer was provided only during IVM, we observed no effects on overall rates of maturation, cleavage, or blastocysts (92.2 ± 1.6%, 78.3 ± 4.1%, and 28.9 ± 5.1%, respectively). However, high doses of each CLA isomer, but not low doses, during the entire embryo culture period decreased blastocyst rates (5-20%) in a dose-dependent manner. Cleavage rates improved with 15 or 50 µM CLA trans-10,cis-12. Progesterone concentrations in maturation media were significantly increased by high doses of each CLA isomer compared with control, but low doses of CLA isomers had no effect. In experiment 2 with IVF embryos, low doses of each CLA isomer did not alter cleavage rates (average 84.9 ± 1.9%) and only 25 µM CLA trans-10,cis-12 during IVC reduced blastocyst rates below those of controls (25.5 ± 2.1 vs. 38.2 ± 2.3%). The lipid content of embryos was increased and relative expression of the BIRC5 (baculoviral IAP repeat containing 5) gene was depressed by CLA trans-10,cis-12. In experiment 3, low doses (15µM) of each CLA isomer during IVC significantly reduced blastocyst rates (20.6 ± 2.4% and 27.7 ± 1.2% vs. 34.18 ± 1.2% for CLA trans-10,cis-12 and CLA cis-9,trans-11 compared with control, respectively) with less effect of each CLA during IVM. In experiment 4, adding 100 µM CLA cis-9,trans-11 during the final 36 h of culture resulted in a high survival rate after rewarming and culture, and the higher embryo blastomere count was comparable to that of control embryos not undergoing vitrification. In conclusion, supplementation with either CLA isomer did not improve embryo production, but inclusion of CLA cis-9,trans-11 before vitrification improved the quality of bovine IVF embryos after rewarming and culture.

Digital holographic microscopy for the evaluation of human sperm structure.

The morphology of the sperm head has often been correlated with the outcome of in vitro fertilization, and has been shown to be the sole parameter in semen of value in predicting the success of intracytoplasmic sperm injection and intracytoplasmic morphologically selected sperm injection. In this paper, we have studied whether digital holographic microscopy (DHM) may be useful to obtain quantitative data on human sperm head structure and compared this technique with high-power digitally enhanced Nomarski optics. The main advantage of digital holography is that high-resolution three-dimensional quantitative sample imaging may be automatically produced by numerical refocusing of a two-dimensional image at different object planes without any mechanical scanning. We show that DHM generates useful information on the dimensions and structure of human sperm, not revealed by conventional phase-contrast microscopy, in particular the volume of vacuoles, and suggest its use as an additional prognostic tool in assisted reproduction technology.