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Treatment with biologics has significantly reduced the social and economic burden of severe asthma. However, some patients may still feature a suboptimal control of their symptoms while on therapy. In this subset of asthmatic patients, a benefit from a dual biologic therapy has sporadically been reported in literature. Our aim is to add our experience to the limited body of evidence supporting combination biologic therapies.Here we present the case of a 68-year-old nonsmoker female, with an allergic and eosinophilic corticosteroid-dependent severe asthma. She displayed well controlled comorbidities and good adherence to the inhaled therapy. Omalizumab was started in 2008 with an initial remarkable clinical improvement. After nine years of biologic therapy, she reported a gradual worsening of her symptoms and exacerbations. Mepolizumab was then added in 2019.The addition of Mepolizumab resulted in a meaningful amelioration of her quality of life, asthma control, number of exacerbations and 6-minute-walking-distance at 3-year follow-up. The average Prednisone dosage was tapered from 25 mg to 20 mg daily. No adverse events were observed since the introduction of the second biologic.Our experience indicates that Mepolizumab may be beneficial and safe as an add-on biologic in a patient whose allergic and eosinophilic asthma remains uncontrolled despite treatment with an anti-IgE strategy. Further studies on a larger number of patients are required to demonstrate whether the positive outcomes published so far are replicable on a larger scale.

Issue d’une famille venant d’Europe de l’Est parlant le yiddish et le russe, Alejandra Pizarnik s’est vue, dès son enfance, confrontée à une autre réalité et à une autre langue. L’idée d’un exil, d’un nomadisme qui nourrit sa vie et son œuvre, est présente dans ses écrits et dans la conscience de son être dans le monde. La notion de voyage et de naufrage seront des images récurrentes. Son langage devient également un langage vagabond propre à une litt-errature. Coming from an Eastern European family that spoke Yiddish and Russian, Alejandra Pizarnik felt, since childhood, in a sort of confrontation with reality and with language. The idea of an exile, of a nomadism that feeds her work and her life, is present in her writing and in her way of being in the world. The notions of journey and sinking will often be present. Her language will also become a wandering language specific to a wandering and rootless literature.

Climate warming may affect multiple aspects of plant life history, including important factors such as germination responses and the key trade-off between offspring size and number. As a case study to address these concepts, we used an alpine plant (waxy bluebell, Wahlenbergia ceracea; Campanulaceae) that shows plasticity to warming in seed traits and in which seed dormancy status regulates germination. We chose an alpine species because alpine environments are ecosystems particularly under threat by climate change. We conducted germination assays under cool and warm temperatures using seeds produced by individuals that were grown under historical (cooler) and future (warmer) temperature scenarios. We assessed the presence of a seed size versus number trade-off, and then examined the effects of seed number and size on germination percentage, the fractions of dormant and viable seeds, and germination velocity. Further, we examined whether warming during parental growth and during germination affected these relationships. We found evidence for a seed size versus number trade-off only under historical parental temperatures. Indeed, under future growth temperatures parental plants produced fewer and smaller seeds and there was no evidence of a trade-off. However, the reductions in both seed traits under warming did not affect germination, despite correlations of seed size and number with germination traits. Warming increased germination, particularly of larger seeds, but overall, it resulted in more than fourfold reductions in parental fitness. Synthesis. Our study shows the importance of growth conditions when evaluating the seed size versus number trade-off. Stressful conditions, such as warmer temperatures, can restrain the ability of plants to reach optimal investment in reproduction, masking the trade-off. By analysing responses across the whole life cycle, we show here an overall detrimental effect of warming, highlighting the potential risk of climate change for Wahlenbergia ceracea, and, potentially, for alpine plant communities more widely.

Purpose Therapeutic strategies for prostate cancer (PCa) have been evolving dramatically worldwide. The current article reports on the evolution of surgical management strategies for PCa in Italy. Methods The data from two independent Italian multicenter projects, the MIRROR-SIU/LUNA (started in 2007, holding data of 890 patients) and the Pros-IT-CNR project (started in 2014, with data of 692 patients), were compared. Differences in patients' characteristics were evaluated. Multivariable logistic regression models were used to identify characteristics associated with robot-assisted (RA) procedure, nerve sparing (NS) approach, and lymph node dissection (LND). Results The two cohorts did not differ in terms of age and prostate-specific antigen (PSA) levels at biopsy. Patients enrolled in the Pros-IT-CNR project more frequently were submitted to RA (58.8% vs 27.6%,p < 0.001) and NS prostatectomy (58.4% vs. 52.9%,p = 0.04), but received LND less frequently (47.7% vs. 76.7%,p < 0.001), as compared to the MIRROR-SIU/LUNA patients. At multivariate logistic models, Lower Gleason Scores (GS) and PSA levels were significantly associated with RA prostatectomy in both cohorts. As for the MIRROR-SIU/LUNA data, clinical T-stage was a predictor for NS (OR = 0.07 for T3, T4) and LND (OR = 2.41 for T2) procedures. As for Pros-IT CNR data, GS >= (4 + 3) and positive cancer cores >= 50% were decisive factors both for NS (OR 0.29 and 0.30) and LND (OR 7.53 and 2.31) strategies. Conclusions PCa management has changed over the last decade in Italian centers: RA and NS procedures without LND have become the methods of choice to treat newly medium-high risk diagnosed PCa.

Understanding plant thermal tolerance is fundamental to predicting impacts of extreme temperature events that are increasing in frequency and intensity across the globe. Extremes, not averages, drive species evolution, determine survival and increase crop performance. To better prioritize agricultural and natural systems research, it is crucial to evaluate how researchers are assessing the capacity of plants to tolerate extreme events. We conducted a systematic review to determine how plant thermal tolerance research is distributed across wild and domesticated plants, growth forms and biomes, and to identify crucial knowledge gaps. Our review shows that most thermal tolerance research examines cold tolerance of cultivated species; c. 5% of articles consider both heat and cold tolerance. Plants of extreme environments are understudied, and techniques widely applied in cultivated systems are largely unused in natural systems. Lastly, we find that lack of standardized methods and metrics compromises the potential for mechanistic insight. Our review provides an entry point for those new to the methods used in plant thermal tolerance research and bridges often disparate ecological and agricultural perspectives for the more experienced. We present a considered agenda of thermal tolerance research priorities to stimulate efficient, reliable and repeatable research across the spectrum of plant thermal tolerance.

Climate change is generating both sustained trends in average temperatures and higher frequency and intensity of extreme events. This poses a serious threat to biodiversity, especially in vulnerable environments, like alpine systems. Phenotypic plasticity is considered to be an adaptive mechanism to cope with climate change in situ, yet studies of the plastic responses of alpine plants to high temperature stress are scarce. Future weather extremes will occur against a background of warmer temperatures, but we do not know whether acclimation to warmer average temperatures confers tolerance to extreme heatwaves. Nor do we know whether populations on an elevational gradient differ in their tolerance or plasticity in response to warming and heatwave events. We investigated the responses of a suite of functional traits of an endemic Australian alpine herb, Wahlenbergia ceracea, to combinations of predicted future (warmer) temperatures and (relative) heatwaves. We also tested whether responses differed between high- vs. low-elevation populations. When grown under warmer temperatures, W. ceracea plants showed signs of acclimation by means of higher thermal tolerance (Tcrit, T50, and Tmax). They also invested more in flower production, despite showing a concurrent reduction in photosynthetic efficiency (Fv/Fm) and suppression of seed production. Heatwaves reduced both photosynthetic efficiency and longevity. However, we found no evidence that acclimation to warmer temperatures conferred tolerance of the photosynthetic machinery to heatwaves. Instead, when exposed to heatwaves following warmer growth temperatures, plants had lower photosynthetic efficiency and underwent a severe reduction in seed production. High- and low-elevation populations and families exhibited limited genetic variation in trait means and plasticity in response to temperature. We conclude that W. ceracea shows some capacity to acclimate to warming conditions but there is no evidence that tolerance of warmer temperatures confers any resilience to heatwaves.

Vitamin D (VitD) deficiency has been reported to be associated with respiratory tract infection. In this work we evaluated the concentration of VitD in COVID-19 patients experiencing acute respiratory infections of different levels of severity excluding those who underwent invasive respiratory support.The levels of serum VitD and C-reactive protein (CRP) were analyzed in 118 consecutive hospitalized COVID-19 patients (74M, 44F), confirmed with rRT-PCR. Of these patients with ventilation support 52 (44.1%) received oxygen via nasal cannula, oxygen mask or an oxygen mask with a reservoir, 48 (40.7%) were on a continuous positive airway pressure device (CPAP) and 18 (15,3%) on non-invasive mechanical ventilation (NIMV).The median values (range) of VitD and of CRP were 15.1 ng/mL (1.3-73.3) and 14.2 mg/L (5.0-151.2), respectively. A negative correlation from VitD levels and those of CRP (correlation coefficient - 0.259: P=0.005) was observed. VitD levels in O2 support patients were significantly higher than in both CPAP and NIMV patients. No statistical differences were found for CRP levels (P=0.834) among the three type of oxygen support. Fewer patients with O2 support had VitD30 ng/mL and20 ng/mL than CPAP and NIMV patients. There were no relationships between VitD and the three classes of IgM (P=0.419) and of IgG (P=0.862) SARS-CoV-2 antibodies values. The behavior was the same for CRP.Our study shows that a significant proportion of COVID-19 patients have a VitD deficiency and that this condition is more frequent in CPAP and in NIMV patients.

Extreme temperature events are increasing in frequency and intensity across the globe. These extremes, rather than averages, drive species evolution and determine survival by profoundly changing the structure and fluidity of cell membranes, altering enzyme function, and denaturing proteins. Given not only our dependence on agricultural crops and natural vegetation, but also the role of photosynthetic processes within the carbon and hydrological cycles, it is imperative to assess the state of our understanding of the potential impacts of extreme events on plants. Scaling responses from the molecular and organ level to ecosystem function is not without challenge however. There is vast literature on plant thermal tolerance research, but the body of literature is so large, the approaches so disparate and often siloed among disciplines, that research in this field risks floundering at a critical time. We conducted a systematic review of more than 21,500 studies spanning over 100 years of research that yielded almost 1,700 included studies on the tolerance of cultivated and wild land plants to both heat and cold. Our review indicates that most studies on thermal tolerance focus on the cold tolerance of cultivated species (52%) and only a trivial percentage of studies have considered both heat and cold tolerance of any given species (~5%). Combined heat and cold tolerance are important in areas where plants are exposed to extremes of both or may be in the future. This review illustrates the global distribution and concentrations of thermal tolerance studies and the diversity of thermal tolerance methods, ranging from molecular to biochemical, physiological and physical examinations, from transgenic model plants to agricultural and horticultural crops, to natural forest trees, shrubs, and grassland herbs. Critically, it also demonstrates that methods and metrics for assessing thermal tolerance are far from standardised, such that our potential to achieve mechanistic insight and compare across species and biomes is compromised. Without reconciling these issues, the scope for incorporating this critical ecological information into vegetation elements of land surface models may be limited. To aid this, we identify priorities for achieving efficient, reliable, and repeatable research across the spectrum of plant thermal tolerance. These priorities, including meta-analytical approaches and comparative experimental work, will not only further fundamental plant science, but will prove essential next steps if we are to integrate such diverse data on a critical plant functional trait into a usable metric within biogeochemical models.

Debilitating symptoms of schizophrenia often persist after sustained treatment with atypical antipsychotics. To date, clozapine has been the most effective of the atypical antipsychotics; however, negative symptoms may persist, indicating a critical need to develop augmenting treatment approaches.A retrospective chart review evaluated outcomes for 5 young adult inpatients with treatment-resistant schizophrenia who were prescribed off-label oxytocin (OT; 10 IU/sublingual, 1 time per day, to 20 IU/sublingual, 3 times per day) after their therapeutic response to clozapine plateaued (dose range: 200 to 600 mg). The augmented treatment was well tolerated and continued for at least 1 year after discharge from the hospital, with continued outpatient follow-up by the treating psychiatrist. Evaluation included the Positive and Negative Syndrome Scale and clinical review based on both self and parent/guardian reports.The augmentation of clozapine with sublingual OT in young adults with treatment-resistant schizophrenia appeared to reduce negative symptoms, maintain lowered positive symptoms, and increase occupational and social functioning (eg, return to work or school), as noted by family members.Future controlled, prospective studies should investigate the possibility that OT can significantly reduce negative symptoms of chronic psychotic illnesses that are inadequately responsive to clozapine or other antipsychotic medications alone.

Background The idea of phenotype in chronic obstructive pulmonary disease (COPD) has evolved in the last decades, and the importance of peculiar treatment strategies has now been acknowledged. Although dyspnea and exercise limitation are hallmarks of COPD, this aspect has never been fully explored in literature in terms of disease phenotype. The aim of the present study was to explore the relevance of clinical COPD phenotypes on exercise ventilation and maximal capacity. Methods In this observational cohort retrospective study we analyzed the data of 50 COPD patients who underwent cardiopulmonary exercise test, categorized as emphysematous (n=29), and non-emphysematous (n=21) according to a previously validated model. Results We found a significant difference in terms of VE/VCO2 slope (median values 32.4 vs 28.0, p=0.015) and VE/VCO2 ratio at nadir (median values 37 vs. 33, p=0.004), which resulted higher in emphysematous patients, who also presented lower PETCO2 values (median values 32.6 vs 35.6, p=0.008). In a subgroup of 31 tests which met the maximality criteria, emphysematous patients presented a significantly lower work rate at peak (median value 51 vs 72% predicted, p=0.016), and showed a lower peak oxygen consumption, although at the limit of significance (median values of 63 vs 85 % predicted, p=0.051). Conclusions This study extends our knowledge about the characterization of the COPD phenotypical expression of disease, showing that patients affected by emphysema are more prone to ventilatory inefficiency during exercise, and that this is likely to be an important cause of their overall reduced exercise capacity.

BACKGROUND: The prevalence of schizophrenia in the United States ranges between 0.5% and 1%. This difficult-to-treat disorder is marked by the presentation of symptoms that are both positive (i.e. hallucinations) and negative (i.e. blunted affect), as well as disturbances in cognition and affect. Several second-generation antipsychotics (i.e. olanzapine, risperidone, etc.) have been utilized for their varying effects on the symptoms of schizophrenia, yet 20% to 60% of patients with schizophrenia are considered treatment-resistant. While clozapine has been shown to be the most effective antipsychotic, negative symptoms commonly persist in clozapine-treated patients. Research shows that oxytocin has neuromodulatory effects on social perception and also enhances empathy and attentional engagement in individuals with schizophrenia, suggesting it has therapeutic effects on negative symptoms. The present study presents a series of cases suggesting the efficacy of combining clozapine and oxytocin for the reduction of positive and negative symptoms. This work contributes to schizophrenia treatment research by reporting a novel, integrated pharmacological approach to treatment-resistant schizophrenia. METHODS: Retrospective chart reviews were conducted on the charts of 15 patients with treatment-resistant schizophrenia. The patients were all admitted to the persistent psychotic disorder unit at a private hospital between May 2014 and September 2017. The average treatment duration was 2.7 months with a range between 1 and 9 months. All patients were 18 years or older and met the DSM-5 criteria for schizophrenia. The Positive and Negative Syndrome Scale (PANSS) was used to assess the efficacy of the combination treatment. Clozapine was prescribed to all 15 patients after they had failed to improve in three different trials of other antipsychotic medications. Intranasal oxytocin (10 IU 2x per day; 20 IU 3x per day) was prescribed to 11 of the patients only after the improvement in positive symptoms on the PANSS with clozapine had plateaued. Due to the risk of intranasal substance use in all the patients, oxytocin was administered sublingually to ensure adequate and less variable absorption of the neuropeptide. RESULTS: Over the course of treatment, PANSS scores reflected significant changes (p

Using time-adaptive probabilistic shaped 64QAM driven by a simple SNR prediction algorithm, we demonstrate $>$450 Gbps transmission over a 55-m free-space optics link with enhanced resilience towards rainy weather conditions. Through continuous measurement over 3-hours, we demonstrate $\sim$40~Gbps average bit-rate gain over unsupervised fixed modulation.

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Background The prevalence of schizophrenia in the United States ranges between 0.5% and 1%. This difficult-to-treat disorder is marked by the presentation of symptoms that are both positive (i.e. hallucinations) and negative (i.e. blunted affect), as well as disturbances in cognition and affect. Several second-generation antipsychotics (i.e. olanzapine, risperidone.) have been utilized for their varying effects on the symptoms of schizophrenia, yet 20% to 60% of patients with schizophrenia are considered treatment-resistant. While clozapine is shown to be the most effective antipsychotic, negative symptoms commonly persist in clozapine-treated patients. Research shows that oxytocin has neuromodulatory effects on social perception and enhances empathy and attentional engagement in individuals with schizophrenia, suggesting it may have therapeutic effects on negative symptoms. The present study presents a pilot prospective research study evaluating the efficacy of combining clozapine and sublingual oxytocin for the reduction of positive and negative symptoms. Methods Prospective research study evaluated 25 treatment resistant schizophrenic patients who were admitted to the persistent psychotic disorder unit at a private hospital, with an average treatment duration of 2.9 months with a range between 1 and 9 months. All have been followed as outpatient for up to 30 months after discharge. All patients were 18 years or older and met the DSM-5 criteria for schizophrenia. The Positive and Negative Syndrome Scale (PANSS) was used to assess the efficacy of the combination treatment. Clozapine was prescribed to all 25 patients after they had failed to improve in three different trials of other antipsychotic medications. Sublingual oxytocin (10 IU 2x per day; 20 IU 3x per day) was prescribed to 25 of the patients only after the improvement in positive symptoms on the PANSS with clozapine had plateaued. Due to a history of intranasal substance use in all the patients, oxytocin was administered sublingual to ensure adequate and less variable absorption of the neuropeptide. Results A time-series analysis demonstrated a significant decrease in PANSS scores across admission, stabilization of clozapine and stabilization of oxytocin (p Discussion The combined effect extends the current research of augmenting sublingual oxytocin and clozapine for individuals with previously treatment-resistant symptoms. Though each patient benefitted from clozapine alone, negative symptoms persisted. Patients, their families, and treatment program staff all observed a significant reduction in the patients’ anxiety and an improvement in the patients’ relatedness. While this case series cannot establish that oxytocin is responsible for the clinical improvements seen here, it does suggest that it may improve negative symptoms and social functioning in patients with treatment-resistant schizophrenia showing incomplete improvement with clozapine alone. The present study suggests the need for future research to explore the possibility that oxytocin can mitigate the negative symptoms of schizophrenia.

Background: A new edition of the TNM was recently released that includes modifications for the staging system of kidney cancers. Specifically, T2 cancers were subclassified into T2a and T2b ( 10 cm), tumors with renal vein involvement or perinephric fat involvement were classified as T3a cancers, and those with adrenal involvement were classified as T4 cancers. Objective: Our aim was to validate the recently released edition of the TNM staging system for primary tumor classification in kidney cancer. Design, setting, and participants: Our multicenter retrospective study consisted of 5339 patients treated in 16 academic Italian centers. Intervention: Patients underwent either radical or partial nephrectomy. Measurements: Univariable and multivariable Cox regression models addressed cancer-specific survival (CSS) after surgery. Results and limitations: In the study, 1897 patients (35.5%) were classified as pT1a, 1453 (27%) as pT1b, 437 (8%) as pT2a, 153 (3%) as pT2b, 1059 (20%) as pT3a, 117 (2%) as pT3b, 26 (0.5%) as pT3c, and 197 (4%) as pT4. At a median follow-up of 42 mo, 786 (15%) had died of disease. In univariable analysis, patients with pT2b and pT3a tumors had similar CSS, as did patients with pT3c and pT4 tumors. Moreover, both pT3a and pT3b stages included patients with heterogeneous outcomes. In multivariable analysis, the novel classification of the primary tumor was a powerful independent predictor of CSS (p for trend < 0.0001). However, the substratification of pT1 tumors did not retain an independent predictive role. The major limitations of the study are retrospective design, lack of central pathologic review, and the small number of patients included in some substages. Conclusions: The recently released seventh edition of the primary tumor staging system for kidney tumors is a powerful predictor of CSS. However, some of the substages identified by the classification have overlapping prognoses, and other substages include patients with heterogeneous outcomes. The few modifications included in this edition may have not resolved the most critical issues in the previous version. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.

International audience; Delineating tumor margins as accurately as possible is of primordial importance in surgical oncology: extent of resection is associated with survival but respect of healthy surrounding tissue is necessary for preserved quality of life. The real-time analysis of the endogeneous fluorescence signal of brain tissues is a promising tool for defining margins of brain tumors. The present study aims to demonstrate the feasibility of multimodal optical analysis to discriminate fresh samples of gliomas, metastases and meningiomas from their appropriate controls. Tumor samples were studied on an optical fibered endoscope using spectral and fluorescence lifetime analysis and then on a multimodal set-up for acquiring spectral, one and two-photon fluorescence images, second harmonic generation signals and two-photon fluorescence lifetime datasets. The obtained data allowed us to differentiate healthy samples from tumor samples. These results confirmed the possible clinical relevance of this real-time multimodal optical analysis. This technique can be easily applied to neurosurgical procedures for a better delineation of surgical margins.

Purpose: The excision of the renal tumor with a substantial margin of healthy parenchyma is considered the gold standard technique for partial nephrectomy. However, simple enucleation showed excellent results in some retrospective series. We compared the oncologic outcomes after standard partial nephrectomy and simple enucleation. Materials and Methods: We retrospectively analyzed 982 patients who underwent standard partial nephrectomy and 537 who had simple enucleation for localized renal cell carcinoma at 16 academic centers between 1997 and 2007. Local recurrence, cancer specific survival and progression-free survival were the main outcomes of this study. The Kaplan-Meier method was used to calculate survival functions and differences were assessed with the log rank statistic. Univariable and multivariable Cox regression models addressed progression-free survival and cancer specific survival. Results: Median followup of the patients undergoing traditional partial nephrectomy and simple enucleation was 51 +/- 37.8 and 54.4 +/- 36 months, respectively (p = 0.08). The 5 and 10-year progression-free survival estimates were 88.9 and 82% after standard partial nephrectomy, and 91.4% and 90.8% after simple enucleation (p = 0.09). The 5 and 10-year cancer specific survival estimates were 93.9% and 91.6% after standard partial nephrectomy, and 94.3% and 93.2% after simple enucleation (p = 0.94). On multivariable analysis the adopted nephron sparing surgery technique was not an independent predictor of progression-free survival (HR 0.8, p = 0.55) and cancer specific survival (HR 0.7, p = 0.53) when adjusted for the effect of the other covariates. Conclusions: To our knowledge this is the first multicenter, comparative study showing oncologic equivalence of standard partial nephrectomy and simple enucleation.

AIM OF THE STUDY: To report a matched-pair comparative analysis between open (OPN) and laparoscopic partial nephrectomy (LPN) for clinical (c) T1a renal masses from a large prospective multicenter dataset. MATERIALS AND METHODS: The RECORd Project includes all patients who underwent OPN and LPN for kidney cancer between January 2009 and January 2011 at 19 Italian centers. Open and laparoscopic groups were compared regarding clinical, surgical, pathologic, functional results and TRIFECTA outcome. Multivariable logistic regression models were used to analyze predictors of WIT >25 min, surgical complications (SC) and the achievement of the TRIFECTA outcome. RESULTS: Overall, 301 patients had OPN and 149 LPN. Groups were matched 1:1 (140 matched pairs) for clinical diameter, tumor location and type of indication. Laparoscopic partial nephrectomy was associated with a significantly mean longer WIT (19.9 vs. 15.1 min; p < 0.001), and it was an independent predictor of a WIT >25 min (RR 6.29, p < 0.0001). The TRIFECTA was achieved in 78.6 and 74.3% after OPN and LPN (p = ns), respectively, and the surgical approach was not a predictor of a negative TRIFECTA and SC at multivariable analysis. At 6-month follow-up, no significant differences were observed between the OPN and LPN group both in estimated glomerular filtration rate (eGFR) (∆GFR 1.1 vs. 4.1 mL/min) and in new-onset stage III-V chronic kidney disease (CKD) rate (0 vs. 0.7%). CONCLUSION: No significant difference in achieving the TRIFECTA outcome was reported after OPN and LPN. LPN was associated with a significantly longer WIT. However, eGFR at 6-month follow-up did not differ significantly between the two surgical approaches.

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Background All bacterial genomes contain repetitive sequences which are members of specific DNA families. Such repeats may occur as single units, or found clustered in multiple copies in a head-to-tail configuration at specific loci. The number of clustered units per locus is a strain-defining parameter. Assessing the length variability of clusters of repeats is a versatile typing methodology known as multilocus variable number of tandem repeat analysis (MLVA). Results Stenotrophomonas maltophilia is an environmental bacterium increasingly involved in nosocomial infections and resistant to most antibiotics. The availability of the whole DNA sequence of the S. maltophilia strain K279a allowed us to set up fast and accurate PCR-based diagnostic protocols based on the measurement of length variations of loci carrying a variable number of short palindromic repeats marking the S. maltophilia genome. On the basis of the amplimers size, it was possible to deduce the number of repeats present at 12 different loci in a collection of S. maltophilia isolates, and therefore label each of them with a digit. PCR-negative regions were labelled 0. Co-amplification of two pairs of loci provided a 4-digit code sufficient for immediate subtyping. By increasing the number of loci analyzed, it should be possible to assign a more specific digit profile to isolates. In general, MLVA data match genotyping data obtained by PFGE (pulsed-field gel electrophoresis). However, some isolates exhibiting the same PCR profiles at all loci display distinct PFGE patterns. Conclusion The utilization of the present protocol allows to type several S. maltophilia isolates in hours. The results are immediately interpretable without the need for sophisticated softwares. The data can be easily reproducible, and compared among different laboratories.

Objective: Diet interventions may reduce the risk of urinary stone formation and its recurrence, but there is no conclusive consensus in the literature regarding the effectiveness of dietary interventions and recommendations about specific diets for patients with urinary calculi. The aim of this study was to review the studies reporting the effects of different dietary interventions for the modification of urinary risk factors in patients with urinary stone disease. Materials and Methods: A systematic search of the Pubmed database literature up to July 1, 2014 for studies on dietary treatment of urinary risk factors for urinary stone formation was conducted according to a methodology developed a priori. Studies were screened by titles and abstracts for eligibility. Data were extracted using a standardized form and the quality of evidence was assessed. Results: Evidence from the selected studies were used to form evidencebased guideline statements. In the absence of sufficient evidence, additional statements were developed as expert opinions. Conclusions: General measures: Each patient with nephrolithiasis should undertake appropriate evaluation according to the knowledge of the calculus composition. Regardless of the underlying cause of the stone disease, a mainstay of conservative management is the forced increase in fluid intake to achieve a daily urine output of 2 liters. Hypercalciuria: Dietary calcium restriction is not recommended for stone formers with nephrolithiasis. Diets with a calcium content ≥ 1 g/day (and low protein-low sodium) could be protective against the risk of stone formation in hypercalciuric stone forming adults. Moderate dietary salt restriction is useful in limiting urinary calcium excretion and thus may be helpful for primary and secondary prevention of nephrolithiasis. A low-normal protein intake decrease calciuria and could be useful in stone prevention and preservation of bone mass. Omega-3 fatty acids and bran of different origin decreases calciuria, but their impact on the urinary stone risk profile is uncertain. Sports beverage do not affect the urinary stone risk profile. Hyperoxaluria: A diet low in oxalate and/or a calcium intake normal to high (800-1200 mg/day for adults) reduce the urinary excretion of oxalate, conversely a diet rich in oxalates and/or a diet low in calcium increase urinary oxalate. A restriction in protein intake may reduce the urinary excretion of oxalate although a vegetarian diet may lead to an increase in urinary oxalate. Adding bran to a diet low in oxalate cancels its effect of reducing urinary oxalate. Conversely, the addition of supplements of fruit and vegetables to a mixed diet does not involve an increased excretion of oxalate in the urine. The intake of pyridoxine reduces the excretion of oxalate. Hyperuricosuria: In patients with renal calcium stones the decrease of the urinary excretion of uric acid after restriction of dietary protein and purine is suggested although not clearly demonstrated. Hypocitraturia: The administration of alkaline-citrates salts is recommended for the medical treatment of renal stone-formers with hypocitraturia, although compliance to this treatment is limited by gastrointestinal side effects and costs. Increased intake of fruit and vegetables (excluding those with high oxalate content) increases citrate excretion and involves a significant protection against the risk of stone formation. Citrus (lemons, oranges, grapefruit, and lime) and non citrus fruits (melon) are natural sources of dietary citrate, and several studies have shown the potential of these fruits and/or their juices in raising urine citrate levels. Children: There are enought basis to advice an adequate fluid intake also in children. Moderate dietary salt restriction and implementation of potassium intake are useful in limiting urinary calcium excretion whereas dietary calcium restriction is not recommended for children with nephrolithiasis. It seems reasonable to advice a balanced consumption of fruit and vegetables and a low consumption of chocolate and cola according to general nutritional guidelines, although no studies have assessed in pediatric stone formers the effect of fruit and vegetables supplementation on urinary citrate and the effects of chocolate and cola restriction on urinary oxalate in pediatric stone formers. Despite the low level of scientific evidence, a low-protein (< 20 g/day) low-salt (< 2 g/day) diet with high hydration (> 3 liters/day) is strongly advised in children with cystinuria. Elderly: In older patients dietary counseling for renal stone prevention has to consider some particular aspects of aging. A restriction of sodium intake in association with a higher intake of potassium, magnesium and citrate is advisable in order to reduce urinary risk factors for stone formation but also to prevent the loss of bone mass and the incidence of hypertension, although more hemodynamic sensitivity to sodium intake and decreased renal function of the elderly have to be considered. A diet rich in calcium (1200 mg/day) is useful to maintain skeletal wellness and to prevent kidney stones although an higher supplementation could involve an increase of risk for both the formation of kidney stones and cardiovascular diseases. A lower content of animal protein in association to an higher intake of plant products decrease the acid load and the excretion of uric acid has no particular contraindications in the elderly patients, although overall nutritional status has to be preserved.

A combination of NMR spectroscopy and molecular modelling techniques has been used to investigate the conformational behaviour in solution of 4-(N)-Squalenoyl-Gemcitabine (Sq-Gem), a promising anticancer new derivative whose pharmacological and biological properties and its use in the medical applications are heavily influenced by its three-dimensional structure. NMR scalar coupling constants (J-couplings) have been experimentally measured, by mono- and bi-dimensional methods, and, subsequently, compared with the theoretically values estimated, via DFT calculations, on the most representative conformations obtained and optimized by molecular 15 dynamics (MD) simulations in methanol solution. Following this approach, we found a good agreement between calculated and experimental NMR data for the major conformations in which the flexible squalenoyl chain is strongly folded.

Study Type - Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? About 80% of RCCs have clear cell histology, and consistent data are available about the clinical and histological characteristics of this histological subtype. Conversely, less attention has been dedicated to the study of non-clear cell renal tumours Specifically, published data show that chromophobe RCC (ChRCC) have often favourable pathological stages and better nuclear grades as well as a lower risk of metastasizing compared with clear cell RCC (ccRCC). Patients with ChRCC were shown to have significantly higher cancer-specific survival (CSS) probabilities compared with ccRCC. However, an independent prognostic role of RCC histotype was not confirmed in some large multicenter series and only a few studies have focused on the oncological outcomes of ChRCC. The present study is one of the few to evaluate cancer-related outcomes of ChRCC and represents to our knowledge the largest series of ChRCCs. Consequently, the present findings may assist in elucidating the natural history of surgically treated ChRCC. The present study confirms that ChRCCs have good prognosis and a low tendency to progress and metastasize. Only 1.3% of patients presented with distant metastases at diagnosis, and the 5- and 10-year CSS were 93% and 88.9%, respectively. However, although ChRCCs are generally characterised by an excellent prognosis, we observed that patients with locally advanced or metastatic cancers as well as those with sarcomatoid differentiation have a poor outcome. The study also investigated prognostic factors for recurrence-free survival (RFS) and CSS for this RCC histotype. The definition of outcome predictors can be useful for patient counselling, planning of follow-up strategies, and patient selection for clinical trials. In the present study, gender, clinical T stage, pathological T stage, and presence of sarcomatoid differentiation were significantly associated with RFS and CSS at multivariable analysis. We also identified N/M stage as an independent predictor of CSS. Notably, as Fuhrman grade was not an independent predictor of cancer-related outcomes, the present study confirms that this histological variable is not a reliable prognostic factor for ChRCC. OBJECTIVES: To investigate cancer-related outcomes of chromophobe renal cell carcinoma (ChRCC) in a large multicentre dataset. To determine prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS) for this RCC histological type. PATIENTS AND METHODS: In all, 291 patients with ChRCC were identified from a multi-institutional retrospective database including 5463 patients who were surgically treated for RCC at 16 Italian academic centres between 1995 and 2007. Univariable and multivariable Cox regression models were used to identify prognostic factors predictive of RFS and CSS after surgery for ChRCC. RESULTS: At a median follow-up of 44 months, 25 patients (8.6%) had disease recurrence and 18 patients (6.2%) died from disease. The 5-year RFS and CSS rates were 89.3% and 93%, respectively. Gender (P= 0.014), clinical T stage (P= 0.017), pathological T stage (P= 0.003), and sarcomatoid differentiation (P= 0.032) were independent predictors of RFS at multivariable analysis. For CSS, there was an independent prognostic role for gender (P= 0.032) and T stage (P= 0.019) among the clinical variables and for T stage (P= 0.016), N/M stage (P= 0.023), and sarcomatoid differentiation (P= 0.015) among the pathological variables. CONCLUSIONS: Patients with ChRCC have a low risk of tumour progression, metastasis, and cancer-specific death. Patient gender, clinical and pathological tumour stage, and sarcomatoid differentiation are significant predictors of RFS and CSS for ChRCC.

Sir, It is with great interest that we read the paper entitled, “A rare case of giant multiseptated thoracic myelomeningocele with segmental placode” by Patnaik and Mahapatra.[4] The authors described a rare presentation of a thoracic spinal dysraphism. The child they presented had no neurological and urologic deterioration, which is very uncommon in a thoracic myelomeningocele, and the magnetic resonance imaging (MRI) showed a multiloculated swelling with a fibroneural stalk that linked the skin malformation to the underlying spinal cord. However, the complete description of the malformation and the fine MRI images and peroperative pictures provided by the authors may not be consistent with the diagnosis of a true myelomeningocele. We believed that it is a form of spinal dysraphism called “limited dorsal myeloschisis” (LDM). Such entity first described in 1993[1] has been nicely reviewed by Pang et al. with its complete description[2] and classification.[3] The case described by Patnaik and Mahapatra would correspond to a typical case of the saccular form. It has the skin-based sac which is filled with cerebrospinal fluid (CSF). The top of the skin lesion is recovered by desquamated tissue which is not normal skin. The neurologic condition is excellent in this case report as reported by Pang et al. in 40–50% of the thoracic and lumbar cases, where the urologic deterioration is only present in 15–20% of the cases.[2] In the present report, MRI findings are also consistent with Pang's description. The fibroneural stalk traverses the CSF-filled sac to reach the top of the skin anomaly. We can see on the axial view that there is a little depression at the junction between the top of the sac and the stalk that corresponds to the skin crater and presumably to the original site of the disjunction failure.[2] There is one very important point brought by the authors: The presence of an evolutive hydrocephalus that required a shunt.[4] This is very interesting as Pang et al. did not report the presence of hydrocephalus in patients with thoracic LDM.[2] This distinction between LDM and myelomeningocele has also an embryological implication: The difference lying in the degree of the neurulation stage.[2] In LDM, only the final stage of the primary neurulation is incomplete. Therefore, a limited disjunction between cutaneous and neural ectoderms is present. It prevents the complete midline skin closure (the top of the sac is covered by desquamated tissue which is not normal skin) and allows persistence of a physical link (fibroneural stalk) between the disjunction site and the dorsal neural tube. This is well documented by the peroperative pictures provided by the authors. The swelling was connected by this stalk to the dura trough a very narrow midline bone defect shown in Figure 3 from Patnaik and Mahapatra.[4] The report from Patnaik and Mahapatra[4] underlines the complexity in the description and classification of spinal dysraphisms. Because these LDMs and myelomeningoceles have such great difference both in the natural history and final outcome, especially at the thoracic level, the proper distinction between these two entities is of paramount importance for a correct management of the child and a proper counseling to the parents.[5] Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

To preserve bovine hides until they are processed into leather, they are often cured in large raceways of saturated brine. This process prevents the growth of most microorganisms, but under some conditions these hides are still susceptible to decomposition by halophilic archaebacteria. Low amounts of porcine bile added to the brine used for curing, have exhibited control of growth of these primitive microorganisms. Reversed‐phase high pressure liquid chromatography (RPHPLC) has been applied to monitor bile concentration in saturated brine mixtures containing contaminants associated with animal hides (bacteria, blood, dirt, fats, hair, manure, urine, etc.). With minimal sample preparation, this method can be used by either the hide curing, packing, or tanning industry to assess the need to charge brine solutions with additional porcine bile during the continuous process of hide addition and removal. Calibration curves of porcine bile added to highly contaminated raceway brine have demonstrated lin...

International audience; no abstract

An observational study was planned by the QuABIOS group, to survey the hormonal treatment administered to prostate cancer patients in Italy within a time window of 12 months. We report here a prospective quality of life (QOL) evaluation over time and by hormonal treatment modalities.Patients with diagnosis of prostate cancer and treated with hormonal therapy were eligible for this study. The EORTC QLQ-C30 v.3 questionnaire was administered at enrolment, after 6 months and after 12 months from enrolment.587 patients were enrolled by 33 urological centers. When 1518 visits were considered together independently of time, antiandrogen monotherapy was associated with a significantly better QOL than LHRH-analogue containing treatment modalities in almost all functional scales; cyproterone acetate demonstrated a better physical function and general health status than bicalutamide. When QOL was analyzed in a prospective 12-month window, a worsening of physical function and general health status was observed, notwithstanding, antiandrogens remained significantly associated to a better QOL than LHRH-analogue therapies also over time: a favourable physical function and general health status appeared again to be related to cyproterone acetate than bicalutamide.Androgen deprivation therapy is associated with decline in QOL, particularly in the domains of physical function, energy, and general health status. This survey demonstrated that antiandrogens had a better QOL profile than LHRH-analogue containing therapies;furthermore, a more favourable tolerability for cyproterone acetate as compared to bicalutamide is suggested.

Objective Platelet-derived growth factor (PDGF) induces cellular proliferation and differentiation by activating intracellular signaling mechanisms via their cognate receptors. In previous studies, we demonstrated that human brain tumors such as meningiomas, astrocytomas, medulloblastomas, and ependymomas expressed the messenger ribonucleic acid for the PDGF subunits and their receptors. In the present study, we investigated the expression of the messenger ribonucleic acid PDGF A and B chains and the PDGF alpha and beta receptors in 17 cases of oligodendrogliomas. Methods Measurements of messenger ribonucleic acid levels were obtained using radioactive complementary deoxyribonucleic acid probes. Protein expression was analyzed with specific antibodies. Results Sixteen of 17 tumors expressed the PDGF A subunit and all the PDGF alpha receptors. Furthermore, all the tumors expressed PDGF B and PDGF beta receptor subunits. Conclusion The results of this study suggest that oligodendrogliomas may have an autocrine loop stimulated by the interaction of PDGF and its receptor simultaneously produced by these tumors.

PURPOSE: We compared [11C]choline-positron emission tomography (PET) with [18F]fluorodeoxyglucose-PET for re-staging prostate cancer in a group of 100 patients. MATERIALS AND METHODS: A total of 100 consecutive patients referred for whole body [18F]fluorodeoxyglucose-PET for clinical prostate re-staging after radical treatment for prostate cancer were retrospectively included in the study. Mean prostate specific antigen (PSA) was 6.57 ng./ml. In all cases [11C]choline-PET was also performed. PET studies were done with a multiring device 5 minutes after intravenous injection of approximately 370 MBq. [11C]choline and 60 minutes after injection of approximately 370 MBq. [18F]fluorodeoxyglucose. PET findings were compared with those obtained with different conventional imaging and with PSA assessed at the time of PET and 1 year later. RESULTS: Areas of abnormal focal increases were noted in 47% of patients on [11C]choline-PET and in 27% on [18F]fluorodeoxyglucose-PET. Of the 100 patients 49 had positive conventional imaging findings. All except 14 [11C]choline-PET findings were concordant with conventional imaging, including 6 negative and 8 positive conventional imaging results. All except 1 [11C]choline-PET negative cases also had negative conventional imaging after 1 year. PSA at 1 year remained stable or decreased in 80% and 62% of [11C]choline-PET negative and positive cases, respectively. CONCLUSIONS: [11C]choline-PET seems to be useful for re-staging prostatectomy cases with increasing serum PSA levels. It is superior to [18F]fluorodeoxyglucose-PET and complementary to conventional imaging but with the advantage of staging disease at a single step.