Polyethylene microplastics alter root functionality and affect strawberry plant physiology and fruit quality traits.

Strawberry, a globally popular crop whose fruit are known for their taste and health benefits, were used to evaluate the effects of polyethylene microplastics (PE-MPs) on plant physiology and fruit quality. Plants were grown in 2-L pots with natural soil mixed with PE-MPs at two concentrations (0.2% and 0.02%; w/w) and sizes (⌀ 35 and 125 µm). Plant physiological responses, root histochemical and anatomical analyses as well as fruit biometric and quality features were conducted. Plants subjected to ⌀ 35 µm/0.2% PE-MPs exhibited the most severe effects in terms of CO2 assimilation due to stomatal limitations, along with the highest level of oxidative stress in roots. Though no differences were observed in plant biomass, the impact on fruit quality traits was severe in ⌀ 35 µm/0.2% MPs treatment resulting in a drop in fruit weight (-42%), soluble solid (-10%) and anthocyanin contents (-25%). The smallest sized PE-MPs, adsorbed on the root surface, impaired plant water status by damaging the radical apparatus, which finally resulted in alteration of plant physiology and fruit quality. Further research is required to determine if these alterations also occur with other MPs and to understand more deeply the MPs influence on fruit physio-chemistry.

Early prediction of endocrine responsiveness in ER+/HER2-negative metastatic breast cancer (MBC): pilot study with 18F-fluoroestradiol (18F-FES) CT/PET.

BACKGROUND: 18F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the endocrine therapy (ET)-FES trial, we evaluated 18F-FES PET/CT as a predictive tool in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). PATIENTS AND METHODS: Eligible patients underwent an 18F-FES PET/CT at baseline. Patients with standardized uptake value (SUV) ≥ 2 received single-agent ET until progressive disease; patients with SUV < 2 were randomized to single-agent ET (arm A) or chemotherapy (ChT) (arm B). The primary objective was to compare the activity of first-line ET versus ChT in patients with 18F-FES SUV < 2. RESULTS: Overall, 147 patients were enrolled; 117 presented with 18F-FES SUV ≥ 2 and received ET; 30 patients with SUV < 2 were randomized to ET or ChT. After a median follow-up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median progression-free survival (PFS) was 12.4 months [95% confidence interval (CI) 3.1-59.6 months] in patients with SUV < 2 randomized to arm A versus 23.0 months (95% CI 7.7-30.0 months) in arm B, [hazard (HR) = 0.71, 95% CI 0.3-1.7 months]; median PFS was 18.0 months (95% CI 11.2-23.1 months) in patients with SUV ≥ 2 treated with ET. Median overall survival (OS) was 28.2 months (95% CI 14.2 months-not estimable) in patients with SUV < 2 randomized to ET (arm A) versus 52.8 months (95% CI 16.2 months-not estimable) in arm B (ChT). Median OS was not reached in patients with SUV ≥ 2. 60-month OS rate was 41.6% (95% CI 10.4% to 71.1%) in arm A, 42.0% (95% CI 14.0% to 68.2%) in arm B, and 59.6% (95% CI 48.6% to 69.0%) in patients with SUV ≥ 2. In patients with SUV ≥ 2, 60-month OS rate was 72.6% if treated with aromatase inhibitors (AIs) versus 40.6% in case of fulvestrant or tamoxifen (P < 0.005). CONCLUSIONS: The ET-FES trial demonstrated that ER+/HER2- MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on 18F-FES CT/PET SUV.

Electroanatomical voltage mapping with contact force sensing for diagnosis of arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Three-dimensional electroanatomical mapping (EAM) can be helpful to diagnose arrhythmogenic right ventricular cardiomyopathy (ARVC). Yet, previous studies utilizing EAM have not systematically used contact-force sensing catheters (CFSC) to characterize the substrate in ARVC, which is the current gold standard to assure adequate tissue contact. OBJECTIVE: To investigate reference values for endocardial right ventricular (RV) EAM as well as substrate characterization in patients with ARVC by using CFSC. METHODS: Endocardial RV EAM during sinus rhythm was performed with CFSC in 12 patients with definite ARVC and 5 matched controls without structural heart disease. A subanalysis for the RV outflow tract (RVOT), septum, free-wall, subtricuspid region, and apex was performed. Endocardial bipolar and unipolar voltage amplitudes (BVA, UVA), signal characteristics and duration as well as the impact of catheter orientation on endocardial signals were also investigated. RESULTS: ARVC patients showed lower BVA vs. controls (p = 0.018), particularly in the subtricuspid region (1.4, IQR:0.5-3.1 vs. 3.8, IQR:2.5-5 mV, p = 0.037) and RV apex (2.5, IQR:1.5-4 vs. 4.3,IQR:2.9-6.1 mV, p = 0.019). BVA in all RV regions yielded a high sensitivity and specificity for ARVC diagnosis (AUC 59-78%, p < 0.05 for all), with the highest performance for the subtricuspid region (AUC 78%, 95% CI:0.75-0.81, p < 0.001, negative predictive value 100%). A positive correlation between BVA and an orthogonal catheter orientation (46°-90°:r = 0.106, p < 0.001), and a negative correlation between BVA and EGM duration (r = -0.370, p < 0.001) was found. CONCLUSIONS: EAM using CFSC validates previous bipolar cut-off values for normal endocardial RV voltage amplitudes. RV voltages are generally lower in ARVC as compared to controls, with the subtricuspid area being commonly affected and having the highest discriminatory power to differentiate between ARVC and healthy controls. Therefore, EAM using CFSC constitutes a promising tool for diagnosis of ARVC.

Thyroid function, sensitivity to thyroid hormones, and metabolic syndrome in euthyroid children and adolescents with Down syndrome.

PURPOSE: Patients with Down Syndrome (DS) showed multiple comorbidities, including thyroid disorders, obesity, and metabolic derangement. Different thyroid hormone (THs) patterns and sensitivity to thyroid hormone indices (STHI) seem to be associated with metabolic disorders. The study's aim was to evaluate the prevalence of metabolic syndrome (MS) in pediatric patients affected by DS, taking into consideration the relationship between the metabolic parameters, THs and STHI. METHODS: We enlisted 50 euthyroid patients with DS (9.03 ± 4.46). Clinical parameters, TSH, FT3, FT4 and the presence of MS were recorded. Indexes of peripheral sensitivity (FT3/FT4 ratio) and central sensitivity (TSH index, TSHI; TSH T4 resistance index, TT4RI; TSH T3 resistance index, TT3RI) were also detected. Thirty healthy subjects were included as a control group. RESULTS: MS was detected in 12% of the subjects with DS. FT3, FT4, and TSH levels were higher in DS than in the control group (p < 0.01); higher levels of FT3/FT4 ratio, TSHI and TT3RI and lower TT4RI values (p < 0.01) were also detected. A significant correlation was detected between FT3 and fasting blood glucose (FBG) (R = 0.46), triglyceride (TG) (r = 0.37), total (r = 0.55) and high density lipoprotein-cholesterol (HDL-C) (r = - 0.38), diastolic blood pressure (DBP) (r = - 0.4); FT3/FT4 ratio and waist circumference (WC) (r = 0.36); TSHI and total (r = 0.30) and HDL cholesterol (r = - 0.31); TT4RI and HDL cholesterol (r = - 0.31); TT3RI and total (r = 0.39) and HDL cholesterol (r = - 032). CONCLUSION: We confirmed a higher MS prevalence in children with DS compared to the control group. A significant association between THs, STHI, and the glucose and lipid metabolism parameters was detected supporting their role in metabolic alterations related to the DS.

Managing chronic disease in the COVID-19 pandemic: an e-learning application to promote a healthy lifestyle for persons with multiple sclerosis.

E-health applications can support continuing care for persons with chronic diseases such as multiple sclerosis (MS). We have developed a web-based mobile app called VIOLA to be used at home by persons with MS (pwMS) who previously participated in an innovative multidisciplinary rehab program. The purpose of VIOLA is to reinforce what participants have learned about a healthy lifestyle and to keep them motivated to adhere to rehabilitation programs. As the outbreak of the Covid-19 pandemic has severely curtailed pwMS contact with their usual health providers, we quickly updated VIOLA to grant continuity of care to our home-bound patients.By monitoring pwMS subscriptions to individual modules, we found a definite increase after the national lockdown was declared. Subscribers rated the app very positively.Encouraged by the positive feedbacks, we are planning to extend the access to our app also to pwMS with no prior specific learning experience. This would limit the psychophysical consequences of the lockdown. Furthermore, VIOLA could be effective in maintaining a proper lifestyle, contributing to improve the quality of life of pwMS.VIOLA has the potential of increasing the adherence of pwMS to the rehabilitation confirming that digital communication tools are a valuable solution for those home-bound.].

The cyto-protective effects of LH on ovarian reserve and female fertility during exposure to gonadotoxic alkylating agents in an adult mouse model.

STUDY QUESTION: Does LH protect mouse oocytes and female fertility from alkylating chemotherapy? SUMMARY ANSWER: LH treatment before and during chemotherapy prevents detrimental effects on follicles and reproductive lifespan. WHAT IS KNOWN ALREADY: Chemotherapies can damage the ovary, resulting in premature ovarian failure and reduced fertility in cancer survivors. LH was recently suggested to protect prepubertal mouse follicles from chemotoxic effects of cisplatin treatment. STUDY DESIGN, SIZE, DURATION: This experimental study investigated LH effects on primordial follicles exposed to chemotherapy. Seven-week-old CD-1 female mice were randomly allocated to four experimental groups: Control (n = 13), chemotherapy (ChT, n = 15), ChT+LH-1x (n = 15), and ChT+LH-5x (n = 8). To induce primary ovarian insufficiency (POI), animals in the ChT and ChT+LH groups were intraperitoneally injected with 120 mg/kg of cyclophosphamide and 12 mg/kg of busulfan, while control mice received vehicle. For LH treatment, the ChT+LH-1x and ChT+LH-5x animals received a 1 or 5 IU LH dose, respectively, before chemotherapy, then a second LH injection administered with chemotherapy 24 h later. Then, two animals/group were euthanized at 12 and 24 h to investigate the early ovarian response to LH, while remaining mice were housed for 30 days to evaluate short- and long-term reproductive outcomes. The effects of LH and chemotherapy on growing-stage follicles were analyzed in a parallel experiment. Seven-week-old NOD-SCID female mice were allocated to control (n = 5), ChT (n = 5), and ChT+LH-1x (n = 6) groups. Animals were treated as described above, but maintained for 7 days before reproductive assessment. PARTICIPANTS/MATERIALS, SETTING, METHODS: In the first experiment, follicular damage (phosphorylated H2AX histone (γH2AX) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay), apoptotic biomarkers (western blot), and DNA repair pathways (western blot and RT-qPCR) were assessed in ovaries collected at 12 and 24 h to determine early ovarian responses to LH. Thirty days after treatments, remaining mice were stimulated (10 IU of pregnant mare serum gonadotropin (PMSG) and 10 IU of hCG) and mated to collect ovaries, oocytes, and embryos. Histological analysis was performed on ovarian samples to investigate follicular populations and stromal status, and meiotic spindle and chromosome alignment was measured in oocytes by confocal microscopy. Long-term effects were monitored by assessing pregnancy rate and litter size during six consecutive breeding attempts. In the second experiment, mice were stimulated and mated 7 days after treatments and ovaries, oocytes, and embryos were collected. Follicular numbers, follicular protection (DNA damage and apoptosis by H2AX staining and TUNEL assay, respectively), and ovarian stroma were assessed. Oocyte quality was determined by confocal analysis. MAIN RESULTS AND THE ROLE OF CHANCE: LH treatment was sufficient to preserve ovarian reserve and follicular development, avoid atresia, and restore ovulation and meiotic spindle configuration in mature oocytes exposed at the primordial stage. LH improved the cumulative pregnancy rate and litter size in six consecutive breeding rounds, confirming the potential of LH treatment to preserve fertility. This protective effect appeared to be mediated by an enhanced early DNA repair response, via homologous recombination, and generation of anti-apoptotic signals in the ovary a few hours after injury with chemotherapy. This response ameliorated the chemotherapy-induced increase in DNA-damaged oocytes and apoptotic granulosa cells. LH treatment also protected growing follicles from chemotherapy. LH reversed the chemotherapy-induced depletion of primordial and primary follicular subpopulations, reduced oocyte DNA damage and granulosa cell apoptosis, restored mature oocyte cohort size, and improved meiotic spindle properties. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This was a preliminary study performed with mouse ovarian samples. Therefore, preclinical research with human samples is required for validation. WIDER IMPLICATIONS OF THE FINDINGS: The current study tested if LH could protect the adult mouse ovarian reserve and reproductive lifespan from alkylating chemotherapy. These findings highlight the therapeutic potential of LH as a complementary non-surgical strategy for preserving fertility in female cancer patients. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Regional Valencian Ministry of Education (PROMETEO/2018/137), the Spanish Ministry of Science and Innovation (CP19/00141), and the Spanish Ministry of Education, Culture and Sports (FPU16/05264). The authors declare no conflict of interest.

Decoding the Evolution of Melanin in Vertebrates.

Melanins are widespread pigments in vertebrates, with important roles in visual signaling, UV protection, and homeostasis. Fossil evidence of melanin and melanin-bearing organelles - melanosomes - in ancient vertebrates may illuminate the evolution of melanin and its functions, but macroevolutionary trends are poorly resolved. Here, we integrate fossil data with current understanding of melanin function, biochemistry, and genetics. Mapping key genes onto phenotypic attributes of fossil vertebrates identifies potential genomic controls on melanin evolution. Taxonomic trends in the anatomical location, geometry, and chemistry of vertebrate melanosomes are linked to the evolution of endothermy. These shifts in melanin biology suggest fundamental links between melanization and vertebrate ecology. Tissue-specific and taxonomic trends in melanin chemistry support evidence for evolutionary tradeoffs between function and cytotoxicity.

Ovarian damage from chemotherapy and current approaches to its protection.

BACKGROUND: Anti-cancer therapy is often a cause of premature ovarian insufficiency and infertility since the ovarian follicle reserve is extremely sensitive to the effects of chemotherapy and radiotherapy. While oocyte, embryo and ovarian cortex cryopreservation can help some women with cancer-induced infertility achieve pregnancy, the development of effective methods to protect ovarian function during chemotherapy would be a significant advantage. OBJECTIVE AND RATIONALE: This paper critically discusses the different damaging effects of the most common chemotherapeutic compounds on the ovary, in particular, the ovarian follicles and the molecular pathways that lead to that damage. The mechanisms through which fertility-protective agents might prevent chemotherapy drug-induced follicle loss are then reviewed. SEARCH METHODS: Articles published in English were searched on PubMed up to March 2019 using the following terms: ovary, fertility preservation, chemotherapy, follicle death, adjuvant therapy, cyclophosphamide, cisplatin, doxorubicin. Inclusion and exclusion criteria were applied to the analysis of the protective agents. OUTCOMES: Recent studies reveal how chemotherapeutic drugs can affect the different cellular components of the ovary, causing rapid depletion of the ovarian follicular reserve. The three most commonly used drugs, cyclophosphamide, cisplatin and doxorubicin, cause premature ovarian insufficiency by inducing death and/or accelerated activation of primordial follicles and increased atresia of growing follicles. They also cause an increase in damage to blood vessels and the stromal compartment and increment inflammation. In the past 20 years, many compounds have been investigated as potential protective agents to counteract these adverse effects. The interactions of recently described fertility-protective agents with these damage pathways are discussed. WIDER IMPLICATIONS: Understanding the mechanisms underlying the action of chemotherapy compounds on the various components of the ovary is essential for the development of efficient and targeted pharmacological therapies that could protect and prolong female fertility. While there are increasing preclinical investigations of potential fertility preserving adjuvants, there remains a lack of approaches that are being developed and tested clinically.

A multidisciplinary analytical framework to delineate spawning areas and quantify larval dispersal in coastal fish.

Assessing larval dispersal is essential to understand the structure and dynamics of marine populations. However, knowledge about early-life dispersal is sparse, and so is our understanding of the spawning process, perhaps the most obscure component of biphasic life cycles. Indeed, poorly known species-specific spawning modality and species-specific early-life traits, as well as the high spatio-temporal variability of the oceanic circulation experienced during larval drift, hamper our ability to appraise the realized connectivity of coastal fishes. Here, we propose an analytical framework which combines Lagrangian modelling, network theory, otolith analyses and biogeographical information to pinpoint and characterize larval sources which are then grouped into discrete spawning areas. Such well-delineated larval sources allow improving the quantitative evaluations of both dispersal scales and connectivity patterns. To illustrate its added value, our approach is applied to two case-studies focusing on Diplodus sargus and Diplodus vulgaris in the Adriatic sea. We evidence robust correlations between otolith geochemistry and modelled spawning areas to assess their relative importance for the larval replenishment of the Apulian coast. Our results show that, contrary to D. sargus, D. vulgaris larvae originate from both eastern and western Adriatic shorelines. Our findings also suggest that dispersal distances and dispersal surfaces scale differently with the pelagic larval duration. Furthermore, 30.8% of D. sargus larvae and 23.6% of D. vulgaris larvae of the Apulian populations originate from Marine protected area (MPA), exemplifying larval export from MPAs to surrounding unprotected areas. This flexible multidisciplinary framework, which can be adjusted to any coastal fish and oceanic system, exploits the explanatory power of a dispersal model, fine-tuned and backed-up by observations, to provide more reliable scientific basis for the management and conservation of marine ecosystems.

Efficacy, Tolerability, and Safety of Low-Volume Bowel Preparations for Patients with Inflammatory Bowel Diseases: The French Multicentre CLEAN Study.

BACKGROUND: Standard high-volume polyethylene glycol [PEG] bowel preparations [PEG-4L] are recommended for patients with inflammatory bowel disease [IBD] undergoing colonoscopy. However, low-volume preparations [≤2 L of active volume] are often used in clinical practice. The aim of this study was to evaluate the efficacy, tolerability, and safety of the various bowel preparations for patients with IBD, including low-volume preparations. METHODS: We conducted a French prospective multicentre observational study over a period of 1 month. Patients aged 18-75 years with IBD with an indication of colonoscopy independent of the study were enrolled. The choice of the preparation was left to the investigators, as per their usual protocol. The patients' characteristics, disease, and colonoscopy characteristics were recorded, and they were given self-reported questionnaires. RESULTS: Twenty-five public and private hospitals enrolled 278 patients. Among them, 46 had a disease flare and 41 had bowel stenoses. Bowel preparations for colonoscopy were as follows: 42% received PEG-2L, 29% received sodium picosulfate [Pico], 15% received PEG-4L, and 14% had other preparations. The preparation did not reach the Boston's score efficacy outcome in the PEG-4L group in 51.2% of the patients [p = 0.0011]. The preparation intake was complete for 59.5% in the PEG-4L group, compared with 82.9% in the PEG-2L group and 93.8% in the Pico group [p < 0.0001]. Tolerability, as assessed by the patients' VAS, was significantly better for both Pico and PEG-2L compared with PEG-4L, and better for Pico compared with PEG-2L [p = 0.008; p = 0.0003]. In multivariate analyses, low-volume preparations were independent factors of efficacy and tolerability. Adverse events occurred in 4.3% of the patients. CONCLUSIONS: Preparations with PEG-2L and Pico were equally safe, with better efficacy and tolerability outcomes compared with PEG-4L preparations. The best efficacy/tolerance/safety profile was achieved with the Pico preparation.

The ERAS Protocol is at the forefront of the peri-operative pathway in colorectal surgery: monocentric clinical study.

INTRODUCTION: Colon cancer is one of the most common neoplastic diseases, with onset in old age; the benefits of the ERAS protocol were evaluated in the peri-operative treatment of patients affected by this neoplasm. METHODS: We studied 90 cases of colorectal neoplasia observed at the General Surgery UOC of the San Camillo de Lellis Hospital between September 2014 and April 2016, undergoing laparoscopic surgery and to which the ERAS protocol was applied; key points were the preoperative oral feeding, the epidural anesthesia, the reduced or failed hydro-electrolytic overload, the early mobilization and recovery of the feeding, the non-use of drainage. The most important parameers considered were the reduced duration of the operating hospital stay, the lower occurrence of early and distant complications. RESULTS: 85 surgical procedures were performed with laparoscopic technique (94.4%) and 5 with traditional open technique (5.6%). The conversion rate was 5.8% (5/85). 29 surgical procedures of right hemicolectomy (32.2%) and 26 of anterior resection of the rectum (28.9%) were performed; in another 29 patients (32.2%) an intervention with an open traditional technique was performed. A balanced anesthesia was performed in 41 patients (45.6%); epidural anesthesia in 32 cases (35.6%); the Tap Block in 17 subjects (18.9%). The average volume of liquid infusion was 1664cc ± 714; the average post-operative hospital stay of 4.3 ± 0.9 days. CONCLUSIONS: The ERAS protocol reduces the duration of the post-operative hospitalization, involves a lower incidence of precocious and remote complications, in particular if associated with a minimally invasive surgical method; it is easily applicable and reproducible in a hospital environment, with a marked reduction in healthcare management costs.

Holocene evolution of Portus Pisanus, the lost harbour of Pisa.

The ancient harbour of Pisa, Portus Pisanus, was one of Italy's most influential seaports for many centuries. Nonetheless, very little is known about its oldest harbour and the relationships between environmental evolution and the main stages of harbour history. The port complex that ensured Pisa's position as an economic and maritime power progressively shifted westwards by coastal progradation, before the maritime port of Livorno was built in the late 16th century AD. The lost port is, however, described in the early 5th century AD as being "a large, naturally sheltered embayment" that hosted merchant vessels, suggesting an important maritime structure with significant artificial infrastructure to reach the city. Despite its importance, the geographical location of the harbour complex remains controversial and its environmental evolution is unclear. To fill this knowledge gap and furnish accurate palaeoenvironmental information on Portus Pisanus, we used bio- and geosciences. Based on stratigraphic data, the area's relative sea-level history, and long-term environmental dynamics, we established that at ~200 BC, a naturally protected lagoon developed and hosted Portus Pisanus until the 5th century AD. The decline of the protected lagoon started at ~1350 AD and culminated ~1500 AD, after which time the basin was a coastal lake.

Combined interventional sialendoscopy and intraductal steroid therapy for recurrent sialadenitis in Sjögren's syndrome: Results of a pilot monocentric trial.

OBJECTIVES: To evaluate the effectiveness of interventional sialendoscopy alone or combined with outpatient intraductal steroid irrigations in patients with sialadenitis due to Sjögren's syndrome (SS). DESIGN: A pilot therapeutic study. SETTING: ENT Clinics, Universities of Milan and Pavia. STUDY POPULATION: We included 22 patients with SS of whom 12 underwent interventional sialendoscopy followed by intraductal steroid irrigations (group A), and 10 interventional sialendoscopy alone (group B). OUTCOMES MEASURES: The following outcome measures were considered and recorded before and after the therapeutic intervention: (i) number of episodes of glandular swelling, (ii) cumulative prevalence of patients with glandular swelling assessed by the specific domain, the EULAR SS Disease Activity Index (ESSDAI), (iii) severity of pain by means of a 0-10 pain visual analogue scale (VAS), (iv) severity of xerostomia and other disease symptoms assessed by the EULAR SS Patient Reported Index (ESSPRI) and the Xerostomia Inventory questionnaire. RESULTS: The postoperative reduction in the mean number of episodes of glandular swelling was 87% (95% CI: 77-93) and 75% (95% CI: 47%-88%) in the groups A and B, respectively. The percentage of patients with glandular swelling decreased from 41.7% to 0.0% in the group A and from 30.0% to 0.0% in the group B, respectively. Most of the patients experienced a subjective clinical improvement documented by the statistically significant reductions in the postoperative mean pain VAS (group A P<.001; group B P=.004), Xerostomia Inventory (P<.001 and P=.003) and ESSPRI scores (P<.001 and P=.008). Interventional sialendoscopy followed by outpatient intraductal steroid irrigations was more effective than interventional sialendoscopy alone, when pain VAS, Xerostomia Inventory and ESSPRI scores before and after treatment were analysed together using the multivariate Hotelling T2 test (P=.0173). CONCLUSIONS: This pilot study confirms that interventional sialendoscopy with steroid duct irrigation significantly reduces the number of painful episodes of sialadenitis and improves the subjective sensation of oral dryness and other disease symptoms in patients with SS. The study results also suggest that the improvement is greater when interventional sialendoscopy is combined with a cycle of outpatient steroid ductal irrigations. Larger controlled randomised studies are certainly needed to confirm these preliminary data.

A White Paper on Global Wheat Health Based on Scenario Development and Analysis.

Scenario analysis constitutes a useful approach to synthesize knowledge and derive hypotheses in the case of complex systems that are documented with mainly qualitative or very diverse information. In this article, a framework for scenario analysis is designed and then, applied to global wheat health within a timeframe from today to 2050. Scenario analysis entails the choice of settings, the definition of scenarios of change, and the analysis of outcomes of these scenarios in the chosen settings. Three idealized agrosystems, representing a large fraction of the global diversity of wheat-based agrosystems, are considered, which represent the settings of the analysis. Several components of global changes are considered in their consequences on global wheat health: climate change and climate variability, nitrogen fertilizer use, tillage, crop rotation, pesticide use, and the deployment of host plant resistances. Each idealized agrosystem is associated with a scenario of change that considers first, a production situation and its dynamics, and second, the impacts of the evolving production situation on the evolution of crop health. Crop health is represented by six functional groups of wheat pathogens: the pathogens associated with Fusarium head blight; biotrophic fungi, Septoria-like fungi, necrotrophic fungi, soilborne pathogens, and insect-transmitted viruses. The analysis of scenario outcomes is conducted along a risk-analytical pattern, which involves risk probabilities represented by categorized probability levels of disease epidemics, and risk magnitudes represented by categorized levels of crop losses resulting from these levels of epidemics within each production situation. The results from this scenario analysis suggest an overall increase of risk probabilities and magnitudes in the three idealized agrosystems. Changes in risk probability or magnitude however vary with the agrosystem and the functional groups of pathogens. We discuss the effects of global changes on the six functional groups, in terms of their epidemiology and of the crop losses they cause. Scenario analysis enables qualitative analysis of complex systems, such as plant pathosystems that are evolving in response to global changes, including climate change and technology shifts. It also provides a useful framework for quantitative simulation modeling analysis for plant disease epidemiology.

Sialendoscope-assisted transoral removal of hilo-parenchymal sub-mandibular stones: surgical results and subjective scores.

It has been suggested that a conservative trans-oral approach to proximal and hilo-parenchymal submandibular stones (HPSMS) is a valid alternative to the more frequently used sialadenectomy. The aim of this study was to evaluate the surgical, ultrasonographic and patients' subjective outcomes of results of the trans-oral removal of HPSMS. Between January 2003 and September 2015, sialendoscope-assisted trans-oral surgery was used to remove symptomatic, large (> 7 mm), fixed and palpable HPSMS from 479 patients under general anaesthesia. All patients were followed clinically and ultrasonographically to investigate symptom relief and recurrence of stones, and were telephonically interviewed to assess saliva-related subjective outcomes with a questionnaire. Stones were successfully removed from 472 patients (98.5%); the seven failures (1.5%) concerned pure parenchymal stones. One year after the procedure, 408 patients (85.1%) were symptom free, 59 (12.3%) had recurrent obstructive symptoms and 12 (2.6%) had recurrent infections. Of the 54 patients who developed a recurrent stone (11.2%), 52 underwent a second procedure: 29 interventional sialendoscopies, two sialendoscope-assisted intra-corporeal pneumatic lithotripsy, eight secondary transoral surgery to remove residual stones, six a cycle of extra-corporeal lithotripsy and seven submandibular sialadenectomy. Most patients (75.2%) reported mild surgery-related pain. The symptoms of 454 patients (94.8%) improved after adjunctive treatment and, at the end of follow-up, the affected gland was preserved in 98.5% of patients. A sialendoscope-assisted trans-oral removal of large HPSMS is a safe, effective, conservative surgical procedure, and functional preservation of the main duct and parenchyma of the obstructed gland allows sialendoscopic access through the natural ostium in case of recurrence. Combining a trans-oral approach with other minimally invasive, conservative procedures ensures symptomatic relief and salivary duct system clearance in the majority of patients.

The role of interventional sialendoscopy and intraductal steroid therapy in patients with recurrent sine causa sialadenitis: a prospective cross-sectional study.

OBJECTIVES: To verify the role of interventional sialendoscopy and steroidal ductal irrigation in patients with recurrent sialadenitis. DESIGN: A prospective, cross-sectional pilot study. SETTING: University of Milan. PARTICIPANTS: Fifty-four patients with sine causa recurrent sialadenitis who underwent interventional sialendoscopy (group A, 36 patients) or interventional sialendoscopy followed by a intraductal steroidal irrigations (group B, 18 patients). MAIN OUTCOMES MEASURES: The number of episodes of sialadenitis three and 6 months before and after sialendoscopy, and their severity assessed by means of a 0-10 pain visual analogue scale. RESULTS: In the population as a whole, a significant post-treatment reduction in the number of episodes of 30.7 ± 5.5 after 3 months and 34.6 ± 10.2 after 6 months (P < 0.001) and a significant reduction in pain visual analogue scale values of 4.7 ± 0.4 after 6 months (P < 0.001) occurred. There was a statistically significant reduction in both parameters at the same time points in both treatment groups (P ≥ 0.001), with no significant between-group difference in pain visual analogue scale values, an albeit non-significant trend in favour of group B in terms of the number of episodes 3 months after therapy that became significant after 6 months (11.0 ± 9.9 versus 20.5 ± 9.5; P = 0.05). CONCLUSIONS: Interventional sialendoscopy is effective for the treatment of recurrent sialadenitis; the addition of intraductal steroidal irrigations seems to increase its value in the medium term. Further studies of larger case series with longer follow-up are needed to establish the possibly primary role of steroid therapy in blocking inflammation.

Production of Pycnidia and Conidia by Guignardia bidwellii, the Causal Agent of Grape Black Rot, as Affected by Temperature and Humidity.

Black rot, caused by the fungus Guignardia bidwellii, is a polycyclic disease affecting grape leaves and berries. In environmentally controlled experiments and in a 3-year field study, the effects of temperature and relative humidity (RH) were assessed on the following growth parameters of G. bidwellii: (i) formation of pycnidia and cirri in grape leaf lesions, (ii) production and germination of conidia, and (iii) length of the period between lesion appearance and pycnidia production. Pycnidia were produced between 5 and 35°C and at 90 to 100% RH but more pycnidia were produced between 20 and 30°C. No pycnidia were produced at RH < 90%. The first pycnidia were produced in approximately 2 days after lesion appearance at ≥20°C and in 8 days at 5°C; pycnidia continued to be produced on the same lesion for 5 to 16 days after lesion appearance, depending on the temperature. Models were developed to describe the effect of temperature and RH on pycnidia production, accounting for 95 and 97% of variability, respectively. Cirri were extruded only between 15 and 35°C and mainly at 100% RH. Field experiments confirmed that pycnidia are produced for several days on a leaf lesion and that the length of the period between lesion appearance and pycnidia production depends on temperature. Overall, the findings showed that production of conidia requires high humidity; under field conditions, some hours at high humidity, which usually occur at nighttime, rather than constant high humidity may be sufficient.

PML-RARA-associated cooperating mutations belong to a transcriptional network that is deregulated in myeloid leukemias.

It has been shown that individual acute myeloid leukemia (AML) patients are characterized by one of few initiating DNA mutations and 5-10 cooperating mutations not yet defined among hundreds identified by massive sequencing of AML genomes. We report an in vivo insertional-mutagenesis screen for genes cooperating with one AML initiating mutations (PML-RARA, oncogene of acute promyelocytic leukemia, APL), which allowed identification of hundreds of genetic cooperators. The cooperators are mutated at low frequency in APL or AML patients but are always abnormally expressed in a cohort of 182 APLs and AMLs analyzed. These deregulations appear non-randomly distributed and present in all samples, regardless of their associated genomic mutations. Reverse-engineering approaches showed that these cooperators belong to a single transcriptional gene network, enriched in genes mutated in AMLs, where perturbation of single genes modifies expression of others. Their gene-ontology analysis showed enrichment of genes directly involved in cell proliferation control. Therefore, the pool of PML-RARA cooperating mutations appears large and heterogeneous, but functionally equivalent and deregulated in the majority of APLs and AMLs. Our data suggest that the high heterogeneity of DNA mutations in APLs and AMLs can be reduced to patterns of gene expression deregulation of a single 'mutated' gene network.

Long-term surgical results in microvascular decompression for hemifacial spasm: efficacy, morbidity and quality of life.

Hemifacial spasm is a condition that may severely reduce patients' quality of life. Microvascular decompression is the neurosurgical treatment of choice. The objective of this work was to describe the efficacy and morbidity of microvascular decompression for hemifacial spasm, evaluate the long-term efficacy on the quality of life and investigate prognostic factors for failure of the procedure. A retrospective study of 446 cases of hemifacial spasm treated by 511 retrosigmoid microvascular decompression over 22 years was conducted. Epidemiological, clinical and imaging findings, treatment modalities and outcomes of patients with pre- and postoperative HSF-8 quality of life questionnaire were studied. Success rate was 82% after first surgery and 91.6% after revision surgery. A low rate of perioperative morbidity was found. Facial palsy was mostly transient (5.5% transient and 0.2% permanent) and cochleovestibular deficit was seen in 4.8% of patients. Revision surgery increased nervous lesions (10.6% to 20.7%). Mean quality of life scores were significantly improved from 18 to 2 over 32, evaluated 7.3 years after surgery. Predictive factors of surgical failure were single conflicts (p = 0.041), atypical vasculo-nervous conflicts involving other vessel than postero-inferior cerebellar artery (p = 0.036), such as vein (p = 0.045), and other compression sites than root exit zone (p = 0.027). Retrosigmoid microvascular decompression is a safe and effective treatment of hemifacial spasm. Revision surgery is not to be excluded in case of failure, but does place patients at risk for more complications. Quality of life is improved in the long-term, indicating objective and subjective satisfaction.

Urological complications following kidney transplantation in pediatric age: A single-center experience.

Surgical complications during kidney transplantation can seriously affect renal outcomes. We assess occurrence, risk factors, and results of all urological complications in a series of renal transplants in a single center. Children who underwent renal transplant between January 2008 and December 2014 were retrospectively evaluated. Postoperative urological complications were reviewed. Demographic details, cause of ESRD, donor type, and surgical procedures at transplant were analyzed. For statistical analysis, the chi-square test or Fisher's exact test were used as appropriate. One hundred and twenty-one kidney transplants were performed in 117 children (median age 12 yr). Sixty-two of 121 (53%) had an underlying urological malformation. At a median follow-up of three yr, 28 urological complications were recorded (23%): 12 lymphocele (10%), 10 ureteral obstruction (8%), three urinary leakage (2.5%), two symptomatic VUR (1.7%), and one hydropyonephrosis. When lymphocele was excluded, the complication incidence rate dropped to 13%. Ureteral obstruction mostly occurred late after transplant (more than six months). Presence of urological malformation was the only factor related to increased occurrence of urological complication (p = 0.007) and, in particular, ureteral obstruction (p = 0.018). Children with urological malformations presented a statistically significant risk of developing urological complications after kidney transplantation, ureteral obstruction being the most common complication.