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.

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.

Ultrasounds application for nut and coffee wastes valorisation via biomolecules solubilisation and methane production.

Lignocellulosic materials (LMs) are abundant feedstocks with excellent potential for biofuels and biocommodities production. In particular, nut and coffee wastes are rich in biomolecules, e.g. sugars and polyphenols, the valorisation of which still has to be fully disclosed. This study investigated the effectiveness of ultrasounds coupled with hydrothermal (i.e. ambient temperature vs 80 °C) and methanol (MeOH)-based pretreatments for polyphenols and sugar solubilisation from hazelnut skin (HS), almond shell (AS), and spent coffee grounds (SCG). The liquid fraction obtained from the pretreated HS was the most promising in terms of biomolecules solubilisation. The highest polyphenols, i.e. 123.9 (±2.3) mg/g TS, and sugar, i.e. 146.0 (±3.4) mg/g TS, solubilisation was obtained using the MeOH-based medium. However, the MeOH-based media were not suitable for direct anaerobic digestion (AD) due to the MeOH inhibition during AD. The water-based liquors obtained from pretreated AS and SCG exhibited a higher methane potential, i.e. 434.2 (±25.1) and 685.5 (±39.5) mL CH4/g glucosein, respectively, than the HS liquors despite having a lower sugar concentration. The solid residues recovered after ultrasounds pretreatment were used as substrates for AD as well. Regardless the pretreatment condition, the methane potential of the ultrasounds pretreated HS, AS, and SCG was not improved, achieving maximally 255.4 (±7.4), 42.8 (±3.3), and 366.2 (±4.2) mL CH4/g VS, respectively. Hence, the solid and liquid fractions obtained from HS, AS, and SCG showed great potential either as substrates for AD or, in perspective, for biomolecules recovery in a biorefinery context.

Fed-batch anaerobic digestion of raw and pretreated hazelnut skin over long-term operation.

This study provided important insights on the anaerobic digestion (AD) of hazelnut skin (HS) by operating a fed-batch AD reactor over 240 days and focusing on several factors impacting the process in the long term. An efficient reactor configuration was proposed to increase the substrate load while reducing the solid retention time during the fed-batch AD of HS. Raw HS produced maximally 19.29 mL CH4/g VSadd/d. Polyphenols accumulated in the reactor and the use of NaOH to adjust the pH likely inhibited AD. Maceration and methanol-organosolv pretreatments were, thus, used to remove polyphenols from HS (i.e. 82 and 97%, respectively) and improve HS biodegradation. Additionally, organosolv pretreatment removed 9% of the lignin. The organosolv-pretreated HS showed an increment in methane potential of 21%, while macerated HS produced less methane than the raw substrate, probably due to the loss of non-structural sugars during maceration.

Systematic review and meta-analysis: Artificial intelligence for the diagnosis of gastric precancerous lesions and Helicobacter pylori infection.

BACKGROUND: The endoscopic diagnosis of Helicobacter-pylori(H.pylori) infection and gastric precancerous lesions(GPL), namely atrophic-gastritis and intestinal-metaplasia, still remains challenging. Artificial intelligence(AI) may represent a powerful resource for the endoscopic recognition of these conditions. AIMS: To explore the diagnostic performance(DP) of AI in the diagnosis of GPL and H.pylori infection. METHODS: A systematic-review was performed by two independent authors up to September 2021. Inclusion criteria were studies focusing on the DP of AI-system in the diagnosis of GPL and H.pylori infection. The pooled accuracy of studies included was reported. RESULTS: Overall, 128 studies were found (PubMed-Embase-Cochrane Library) and four and nine studies were finally included regarding GPL and H.pylori infection, respectively. The pooled-accuracy(random effects model) was 90.3%(95%CI 84.3-94.9) and 79.6%(95%CI 66.7-90.0) with a significant heterogeneity[I2=90.4%(95%CI 78.5-95.7);I2=97.9%(97.2-98.6)] for GPL and H.pylori infection, respectively. The Begg's-test showed a significant publication-bias(p = 0.0371) only among studies regarding H.pylori infection. The pooled-accuracy(random-effects-model) was similar considering only studies using CNN-model for the diagnosis of H.pylori infection: 74.1%[(95%CI 51.6-91.3);I2=98.9%(95%CI 98.5-99.3)], Begg's-test(p = 0.1416) did not show publication-bias. CONCLUSION: AI-system seems to be a good resource for an easier diagnosis of GPL and H.pylori infection, showing a pooled-diagnostic-accuracy of 90% and 80%, respectively. However, considering the high heterogeneity, these promising data need an external validation by randomized control trials and prospective real-time studies.

Diagnostic Accuracy of EndoFaster® and Narrow-Band Imaging Endoscopy in Patients with Impaired Gastric Acid Secretion: A Real-Time Prospective Study.

BACKGROUND: EndoFaster® analyzes gastric juice in real time during gastroscopy allowing the detection of hypo-achlorhydric conditions, like corpus atrophic gastritis. Narrow-band imaging (NBI) endoscopy allows to accurately detect and perform target biopsies in areas of intestinal metaplasia, a histological change often associated to corpus atrophic gastritis. AIMS: To compare the diagnostic accuracy of EndoFaster® with histological evaluation for corpus atrophic gastritis through high-resolution (HR) NBI targeted biopsies. METHODS: Prospective study on consecutive adult patients undergoing gastroscopy between April and November 2018. Patients in therapy with proton pump inhibitors, previous gastric surgery, and/or known gastric neoplasia were excluded. At the beginning of gastroscopy, gastric juice was aspirated and analyzed by EndoFaster® in 15 seconds. Endoscopists were blinded to the report of EndoFaster®. Evaluation of gastric mucosa in HR-white light was firstly performed, then with HR-NBI allowing to perform targeted biopsies on areas suspected for intestinal metaplasia; otherwise, biopsies were performed according to the updated Sydney System protocol and sent for histopathological evaluation. RESULTS: Overall, 124 patients were included [64% F; 56 (18-85) years]. Corpus atrophic gastritis was present in 41.9% of patients. EndoFaster® showed an accuracy for corpus atrophic gastritis diagnosis, compared to histopathological evaluation as gold standard, of 87.1% and a sensitivity, specificity, PPV, and NPV of 78.8%, 93.1%, 89.1%, and 85.9%, respectively. pH showed a positive correlation with the severity score of atrophy (r = 0.67, 95% CI: 0.73-0.81, and p < 0.0001). EndoFaster® allowed to diagnose corpus atrophic gastritis in 3.7% of patients negative to NBI (corpus atrophic gastritis without intestinal metaplasia). CONCLUSION: EndoFaster® seems a promising tool to diagnose corpus atrophic gastritis. The evaluation of hypo-achlorhydria during gastroscopy can address bioptic sampling in corpus atrophic gastritis patients without intestinal metaplasia.

Removal of polycyclic aromatic hydrocarbons during anaerobic biostimulation of marine sediments.

This study proposes the supplementation of digestate, fresh organic fraction of municipal solid waste (OFMSW) and a nutrient solution during the anaerobic biostimulation of marine sediments contaminated by polycyclic aromatic hydrocarbons (PAHs). The experimental activity was conducted with four PAHs (i.e. phenanthrene, anthracene, fluoranthene and pyrene) under controlled mesophilic conditions (37 ± 1 °C) in 100 mL serum bottles maintained at 130 rpm. After 120 days of incubation, the highest total PAH degradation of 53 and 55% was observed in the experiments with digestate + nutrients and OFMSW + nutrients, respectively. Phenanthrene was the most degraded PAH and the highest removal of 69% was achieved with OFMSW + nutrients. The anaerobic PAH degradation proceeded through the accumulation of volatile fatty acids and the production of hydrogen and methane as biogas constituents. The highest cumulative biohydrogen production of 80 mL H2·g VS-1 was obtained when OFMSW was used as the sole amendment, whereas the highest biomethane yield of 140 mL CH4·g VS-1 was obtained with OFMSW + nutrients. The evolution of PAH removal during anaerobic digestion revealed a higher impact of the methanogenic phase rather than acidogenic phase on PAH degradation.

Multiple effectiveness aspects of tapentadol for moderate-severe cancer-pain treatment: an observational prospective study.

BACKGROUND: Previous studies have shown the efficacy of tapentadol (TP) for chronic cancer pain. We evaluated multiple effectiveness aspects of TP prolonged release on moderate-severe cancer-related pain, neuropathic pain (NeP), patient satisfaction, and quality of life. METHODS: An observational prospective study was conducted on 80 cancer patients. Opioid-naïve patients received a starting dose of prolonged-release TP 50 mg twice daily, and opioid-experienced patients were switched to TP, not to exceed 500 mg/day. Treatment response was evaluated at 3, 6, 30-40, and 60-70 days through response rate, numeric rating-scale scoring, survival analysis (time to event for response), pain-intensity difference, TP escalation-index percentage, and effects on NeP. The drug-sparing effect on concomitant therapies was evaluated. RESULTS: Seventy of 80 patients (88%) were responders to treatment (95% CI 78%-94%). Compared to T0, pain-intensity reductions were statistically significant for all intervals (P<0.01), with better results at T3/T4. NeP was significantly reduced at T4 (P<0.01). The probability of response was low at the initial stages and increased during the study. Pain-intensity differences decreased during the study, though without significance. Two patients (2.5%) left the study for TP-induced side effects. A significant improvement in quality of life was observed after 30-40 days (P<0.01). The majority of patients were "satisfied", "very satisfied", or "extremely satisfied" (T3-T4). CONCLUSION: TP was effective in terms of drug-sparing effect, response rate, TP escalation-index percentage, and NeP management. By comparing data from the survival analysis with the response rate and time to response (numeric rating scale from T0 to T4), we found that although TP induced a quick response, a longer period of therapy and higher doses were needed to improve the positive result.

Detecting a rare composite small bowel lymphoma by Magnetic Resonance Imaging coincidentally: A case report with radiological, surgical and histopathological features.

INTRODUCTION: Diagnosing lymphoma continues to prove challenging in the clinical practice. Composite lymphoma (CL) is defined by the coexistence of different lymphoma subtypes in the same anatomical location. This condition has seldom been witnessed in the gastrointestinal (GI) tract. We weren't able to find previous cases in the literature about small bowel CL with follicular lymphoma (FL) and classical Hodgkin lymphoma (CHL). Surgery is the treatment of choice to obtain accurate histology, to manage and prevent acute complications. We state that this work has been reported in line with the SCARE criteria. CASE PRESENTATION: We describe an extremely rare case of small bowel CL, presenting as an intestinal bulky mass with circumferential infiltration of bowel loops. The small bowel tumor was incidentally detected by abdominal Magnetic Resonance Imaging (MRI) in a 64-year-old man who suffered from rectal discomfort and non-specific clinical symptoms. After this radiological finding, the patient underwent multiphase contrast computed tomography (MDCT) for initial staging and to study vascular involvement. Surgery was recommended to obtain an accurate diagnosis both due to initial symptoms of the intestinal obstruction and to avoid small bowel complications. The histopathological examination revealed a small bowel CL composed mainly of B cells FL with also CHL components. CONCLUSION: It is important to note that involvement of the proximal ileal loops is very rare in small bowel lymphoma. MRI represents a precious diagnostic tool to evaluate the intra and extramural extent of the tumor.

Divergence Excess Intermittent Exotropia: Long-Term Effect of Augmented Bilateral Lateral Rectus Recession.

PURPOSE: To investigate the long-term (10 years) effects of augmented bilateral lateral rectus (aBLR) recession in patients affected by divergence excess intermittent exotropia (deIXT). METHODS: Data of 58 patients affected by deIXT who underwent aBLR muscle recession were retrospectively analyzed. All patients were treated with 8.0 to 9.5 mm (mean 8.6 ± 0.5 mm) recession of BLR. RESULTS: Our result showed a significant decreasing of both distance and near residual deviation during follow-up. The percentage of patients with successful surgical outcome (defined as a residual deviation ranging from 10pd intermittent exotropia to 5pd esotropia) increased during follow-up (from 51.7% to 81% at last follow-up). Stereopsis increased in 39.7% of patients at last follow-up. Moreover, there was a significant correlation between age at surgery and short/mid-term residual deviation. CONCLUSIONS: Our long-term results suggest that aBLR recession surgery is a very effective approach in patients affected by deIXT.

Epidemiology of endometriosis and its comorbidities.

Genetic profile, inflammation, hormonal activity, menstrual cyclicity, organochlorine burden, prostaglandin metabolism and immunological factors have been suggested to play a role in the establishment and development of endometriosis. From the epidemiological perspective, several risk factors have been studied to suggest or support the different aetiological hypotheses. Social class and family history apart, the factors most consistently associated with endometriosis are early age at menarche and long and heavy menstrual cycles. These menstrual characteristics (together with nulliparity) reflect increased exposure to menstruation. The other main risk factors are pigmentary traits and sun habits, alcohol intake, use of oral contraceptives, and environmental factors such as exposure to polychlorinated biphenyls and dioxin. All of these factors support a potential role of hormonal mileau and inflammation in the pathogenesis of endometriosis. There is a clear association between endometriosis and gastrointestinal and immunological diseases, ovarian cancer and other gynaecological cancers, and thyroid cancer.

Calibration of GafChromic EBT3 for absorbed dose measurements in 5 MeV proton beam and (60)Co γ-rays.

PURPOSE: To study EBT3 GafChromic film in low-energy protons, and for comparison purposes, in a reference (60)Co beam in order to use it as a calibrated dosimetry system in the proton irradiation facility under construction within the framework of the Oncological Therapy with Protons (TOP)-Intensity Modulated Proton Linear Accelerator for RadioTherapy (IMPLART) Project at ENEA-Frascati, Italy. METHODS: EBT3 film samples were irradiated at the Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali di Legnaro, Italy, with a 5 MeV proton beam generated by a 7 MV Van de Graaff CN accelerator. The nominal dose rates used were 2.1 Gy/min and 40 Gy/min. The delivered dose was determined by measuring the particle fluence and the energy spectrum in air with silicon surface barrier detector monitors. A preliminary study of the EBT3 film beam quality dependence in low-energy protons was conducted by passively degrading the beam energy. EBT3 films were also irradiated at ENEA-National Institute of Ionizing Radiation Metrology with gamma radiation produced by a (60)Co source characterized by an absorbed dose to water rate of 0.26 Gy/min as measured by a calibrated Farmer type ionization chamber. EBT3 film calibration curves were determined by means of a set of 40 film pieces irradiated to various doses ranging from 0.5 Gy to 30 Gy absorbed dose to water. An EPSON Expression 11000XL color scanner in transmission mode was used for film analysis. Scanner response stability, intrafilm uniformity, and interfilm reproducibility were verified. Optical absorption spectra measurements were performed on unirradiated and irradiated EBT3 films to choose the most sensitive color channel to the dose range used. RESULTS: EBT3 GafChromic films show an under response up to about 33% for low-energy protons with respect to (60)Co gamma radiation, which is consistent with the linear energy transfer dependence already observed with higher energy protons, and a negligible dose-rate dependence in the 2-40 Gy/min range. Short- and long-term scanner stabilities were 0.5% and 1.5%, respectively; film uniformity and reproducibility were better than 0.5%. CONCLUSIONS: The main purpose of this study was to implement EBT3 dosimetry in the proton low-energy radiobiology line of the TOP-IMPLART accelerator, having a maximum energy of 7 MeV. Low-energy proton and (60)Co calibrated sources were used to investigate the behavior of film response vs to be written in italicum dose. The calibration in 5 MeV protons is currently used for dose assessment in the radiobiological experiments at the TOP-IMPLART accelerator carried out at that energy value.

Glioblastoma stem cells: radiobiological response to ionising radiations of different qualities.

Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumour, with very poor prognosis. The high recurrence rate and failure of conventional treatments are expected to be related to the presence of radio-resistant cancer stem cells (CSCs) inside the tumour mass. CSCs can both self-renew and differentiate into the heterogeneous lineages of cancer cells. Recent evidence showed a higher effectiveness of C-ions and protons in inactivating CSCs, suggesting a potential advantage of Hadrontherapy compared with conventional radiotherapy for GBM treatment. To investigate the mechanisms involved in the molecular and cellular responses of CSCs to ionising radiations, two GBM stem cell (GSC) lines, named lines 1 and 83, which were derived from patients with different clinical outcomes and having different metabolic profiles (as shown by NMR spectroscopy), were irradiated with (137)Cs photons and with protons or C-ions of 62 MeV u(-1) in the dose range of 5-40 Gy. The biological effects investigated were: cell death, cell cycle progression, and DNA damage induction and repair. Preliminary results show a different response to ionising radiation between the two GSC lines for the different end points investigated. Further experiments are in progress to consolidate the data and to get more insights on the influence of radiation quality.

Induction and Repair of DNA DSB as Revealed by H2AX Phosphorylation Foci in Human Fibroblasts Exposed to Low- and High-LET Radiation: Relationship with Early and Delayed Reproductive Cell Death.

The spatial distribution of radiation-induced DNA breaks within the cell nucleus depends on radiation quality in terms of energy deposition pattern. It is generally assumed that the higher the radiation linear energy transfer (LET), the greater the DNA damage complexity. Using a combined experimental and theoretical approach, we examined the phosphorylation-dephosphorylation kinetics of radiation-induced γ-H2AX foci, size distribution and 3D focus morphology, and the relationship between DNA damage and cellular end points (i.e., cell killing and lethal mutations) after exposure to gamma rays, protons, carbon ions and alpha particles. Our results showed that the maximum number of foci are reached 30 min postirradiation for all radiation types. However, the number of foci after 0.5 Gy of each radiation type was different with gamma rays, protons, carbon ions and alpha particles inducing 12.64 ± 0.25, 10.11 ± 0.40, 8.84 ± 0.56 and 4.80 ± 0.35 foci, respectively, which indicated a clear influence of the track structure and fluence on the numbers of foci induced after a dose of 0.5 Gy for each radiation type. The γ-H2AX foci persistence was also dependent on radiation quality, i.e., the higher the LET, the longer the foci persisted in the cell nucleus. The γ-H2AX time course was compared with cell killing and lethal mutation and the results highlighted a correlation between cellular end points and the duration of γ-H2AX foci persistence. A model was developed to evaluate the probability that multiple DSBs reside in the same gamma-ray focus and such probability was found to be negligible for doses lower than 1 Gy. Our model provides evidence that the DSBs inside complex foci, such as those induced by alpha particles, are not processed independently or with the same time constant. The combination of experimental, theoretical and simulation data supports the hypothesis of an interdependent processing of closely associated DSBs, possibly associated with a diminished correct repair capability, which affects cell killing and lethal mutation.

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.

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.

Histological recovery and gluten-free diet adherence: a prospective 1-year follow-up study of adult patients with coeliac disease.

BACKGROUND: Adequate gluten-free diet (GFD) is the only treatment for coeliac disease (CD). However, no agreement has been reached on either how and when to assess patient adherence to GFD or its effectiveness on villous atrophy. AIM: To assess, in a prospective study, patient adherence to and efficacy of GFD on histological recovery after 1-year of GFD. METHODS: Between 2009 and 2012, we enrolled 65 consecutive newly-diagnosed adult patients (median age 38 years, 18-70) with biopsy-proven atrophic CD. Patients were re-evaluated after 1 year of GFD with duodenal histology, serological assays, symptoms and a dietary interview based on a validated questionnaire. Complete histological recovery was defined as the absence of villous atrophy and ≤30/100 intraepithelial lymphocytes. RESULTS: Overall, 81.5% of patients had adequate adherence (ADA) to GFD, whereas 18.5% had an inadequate adherence (IADA); 66% of ADA patients and no IADA patients achieved complete histological recovery (P < 0.00001). Among ADA patients, antibody seroconversion and symptoms were not significantly different between patients who achieved complete histological recovery and those who achieved partial histological recovery with P = 0.309 and P = 0.197, respectively. Multivariate analysis showed that Marsh 3C was a risk factor for incomplete histological recovery in ADA patients (OR 8.74, 95% CI: 1.87-40.83). CONCLUSIONS: This study shows that complete histological recovery after 1-year of GFD in adult patients, who are assessed as adherent to the GFD, can be obtained in 66% of patients. Patients with severe histological damage at diagnosis are at risk for incomplete histological recovery 1 year later.

Indocyanine green video-angiography in neurosurgery: a glance beyond vascular applications.

OBJECTIVE: Indocyanine green video angiography (ICG-VA) is a non invasive, easy to use and a very useful tool for various neurosurgical procedures. Initially introduced in vascular neurosurgery since 2003, it's applications have broadened over time, both in vascular applications and in other neurosurgical fields. The objective of our study is to review all published literature about ICG-VA, cataloguing its different applications. METHODS: A systematic review of all pertinent literature articles published from January 2003 to May 2014 using Pubmed access was performed using pertinent keywords; cross check of references of selected articles was performed in order to complete bibliographical research. Results of research were grouped by pathology. RESULTS AND CONCLUSIONS: The paper systematically analyses ICG-VA different applications in neurosurgery, from vascular neurosurgery to tumor resection and endoscopic applications, focusing on reported advantages and disadvantages, and discussing future perspectives.

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.

New perspectives for transcatheter aortic valve implantation: more than a "simple" alternative to surgery.

To date, the gold standard of aortic stenosis treatment is surgical valve replacement. However, in inoperable or high risk patients a valid alternative is transcatheter aortic valve implantation (TAVI). Several trials showed feasibility, efficacy and safety of TAVI, with a tailored strategy for these patients on the basis of their clinical and anatomical conditions. The selection of valve type (CoreValve® or Edwards Sapien®) and transcatheter approach (transfemoral, transapical, subclavian or direct aortic approach) is an important step in the management of aortic stenosis. However, mortality is high and it is mainly related to non-cardiac reasons, given the high clinical risk profile of these patients. Moreover, the less invasive approach, the faster recovery, the reduced morbidity and the improved psychological tolerance, typical of TAVI, suggest that this technique could be used in a broader spectrum of cases, becoming a valid therapeutic alternative even in patients with severe aortic stenosis with a low surgical risk or asymptomatics. The identification of aortic stenosis patients by the medical community and their assessment over time, before they become candidates only for "extreme" strategies, remains the main challenge.