Multi-target assessment of advanced oxidation processes-based strategies for indirect potable reuse of tertiary wastewater: Fate of compounds of emerging concerns, microbial and ecotoxicological parameters.

Two advanced oxidation processes (AOPs), namely ozone/H2O2 and UV/H2O2, were tested at pilot scale as zero-liquid-discharge alternative treatments for the removal of microbiological (bacteria and viruses), chemical (compounds of emerging concern (CECs)) and genotoxic responses from tertiary municipal wastewater for indirect potable reuse (IPR). The AOP treated effluents were further subjected to granular activated carbon (GAC) adsorption and UV disinfection, following the concept of multiple treatment barriers. As a reference, a consolidated advanced wastewater treatment train consisting of ultrafiltration, UV disinfection, and reverse osmosis (RO) was also employed. The results showed that, for the same electrical energy applied, the ozone/H2O2 treatment was more effective than the UV/H2O2 treatment in removing CECs. Specifically, the ozone/H2O2 treatment, intensified by high pressure and high mixing, achieved an average CECs removal efficiency higher than UV/H2O2 (66.8% with respect to 18.4%). The subsequent GAC adsorption step, applied downstream the AOPs, further improved the removal efficiency of the whole treatment trains, achieving rates of 98.5% and 96.8% for the ozone/H2O2 and UV/H2O2 treatments, respectively. In contrast, the ultrafiltration step of the reference treatment train only achieved a removal percentage of 22.5%, which increased to 99% when reverse osmosis was used as the final step. Microbiological investigations showed that all three wastewater treatment lines displayed good performance in the complete removal of regulated and optional parameters according to both national and the European Directive 2020/2184. Only P. aeruginosa resulted resistant to all treatments with a higher removal by UV/H2O2 when higher UV dose was applied. In addition, E. coli STEC/VTEC and enteric viruses, were found to be completely removed in all tested treatments and no genotoxic activity was detected even after a 1000-fold concentration. The obtained results suggest that the investigated treatments are suitable for groundwater recharge to be used as a potable water source being such a procedure an IPR. The intensified ozone/H2O2 or UV/H2O2 treatments can be conveniently incorporated into a multi-barrier zero-liquid-discharge scheme, thus avoiding the management issues associated with the retentate of the conventional scheme that uses reverse osmosis. By including the chemical cost associated with using 11-12 mg/L of H2O2 in the cost calculations, the overall operational cost (energy plus chemical) required to achieve 50% average CECs removal in tertiary effluent for an hypothetical full-scale plant of 250 m3/h (or 25,000 inhabitants) was 0.183 €/m3 and 0.425 €/m3 for ozone/H2O2 and UV/H2O2 treatment train, respectively.

Food applications of Irvingia gabonensis (Aubry-Lecomte ex. O'Rorke) Baill., the 'bush mango': A review.

Irvingia gabonensis, also known as 'bush mango', is a multipurpose fruit tree, native to tropical Africa. It is a priority indigenous fruit tree in western and central Africa since its wood is used for making utensils and fruits are mostly used as food and medicine. The objective of this work is to provide an updated review of the available knowledge about physicochemical characteristics of I. gabonensis fruit in order to evaluate its potential use in the food industry. The fruit mesocarp contains various phytochemicals and ascorbic acid concentration higher than some vitamin C rich fruits, then it is consumed fresh or dried, used to produce juice and wine, or as a flavourant. I. gabonensis fruit kernel is rich in oil (63%-69% crude fat), mainly composed of myristic and lauric acids. Its triacylglycerol composition and, resultantly, melting curve and polymorphism indicate an aptitude for diverse applications, as it is solid at room temperature. Forty-one phenolic compounds were identified in the seeds and derived extracts and supplements, being ellagic acid and its derivates the most present. This review enhances our knowledge about nutritional content and health benefits of I. gabonensis whole fruit, especially its pulp and seed, evidencing the need for safer and more efficient production of value-added products.

Brain alterations in GABA, glutamate and glutamine markers after chronic atrazine exposure in the male albino rat.

Atrazine (ATR; 2-chloro-4-ethylamino-6-isopropylamino-s-triazine) is an herbicide widely used to kill annual grasses and broadleaf weeds in crops such as corn, sorghum, and sugarcane. Studies in rodents have shown that chronic ATR exposure is associated with alterations in the nigrostriatal dopaminergic pathway such as hyperactivity, decreased striatal dopamine levels, and diminished numbers of tyrosine hydroxylase positive cells in substantia nigra pars compacta. However, the effects of ATR on neurotransmitters such as GABA and glutamate have been scarcely studied. To evaluate the impact of ATR on motor and anxiety tasks, tissue levels of GABA, glutamate, glutamine, and extracellular and potassium-evoked release of glutamate in the striatum, we daily exposed Sprague-Dawley male rats to 1 or 10 mg ATR/kg of body weight for 12-14 months. As previously reported, chronic ATR exposure causes hyperactivity in the group exposed to 10 mg ATR/kg and increased anxiety in both groups exposed to ATR. GABA, glutamate, and glutamine levels were differentially altered in brain regions related to nigrostriatal and mesolimbic systems, the amygdala, and the prefrontal cortex. The groups exposed to 10 mg ATR/kg showed increased extracellular levels and release of glutamate in the striatum. These neurochemical alterations could underlie the behavioral changes observed in rats. These results indicate that chronic exposure to the herbicide ATR disrupts the neurochemistry of several brain structures and could be a risk factor for the development of neurodegenerative diseases.

Enteric Viruses in Surface Waters from Argentina: Molecular and Viable-Virus Detection.

Water resources contaminated with wastewater are an important source for the dissemination of enteric viruses with an impact on the health of the population. The aim of the study was to assess the viral contamination of freshwater from a dam in Argentina by using infectious enterovirus detection, viral RNA amplification, and a genetic characterization of five enteric viruses associated with diarrhea and hepatitis. Enterovirus infectivity (iEV) was evaluated by cell culture and direct immunofluorescence. The detection of the viral genome of rotavirus (RV), human astrovirus (HAstV), norovirus (NoV), hepatitis A virus (HAV), and hepatitis E virus (HEV) was performed by reverse transcriptase PCR (RT-PCR). A total of 48 water samples from 4 monitoring points on the body of the dam from January to December 2012 and 66 water samples from 3 tourist beaches on the edge of the dam from October 2013 to October 2015 were collected monthly. During the first period, the overall viral frequency detection was 52.1% for group A RV, 50% for HAstV, 60.4% for NoV, 22.9% for HAV, 2.1% for HEV, and 64.6% for iEV. The overall frequency detection for the second sampling was 18.2% for RV and HAstV, 31.8% for NoV, 7.57% for HEV, and 66.7% for iEV. There was no detection of HAV during this period. The genotypes and genogroups detected through the study correlated with the most common genomic variants associated with human gastrointestinal and hepatitis illnesses. The results obtained could alert the health systems and environmental sanitation to make decisions for viral control and prevention in our environment.IMPORTANCE The study shows the impact of anthropic contamination of one of the most important tourist water resources in Argentina. This course of recreational water would be a favorable scenario for infection, as well as a reservoir for the enteric viruses, creating a risk for the population exposed to these waters. The results obtained could alert the health systems and environmental sanitation to make decisions for the control and prevention of viral diseases in this environment.

HX600, a synthetic agonist for RXR-Nurr1 heterodimer complex, prevents ischemia-induced neuronal damage.

Ischemic stroke is amongst the leading causes of death and disabilities. The available treatments are suitable for only a fraction of patients and thus novel therapies are urgently needed. Blockage of one of the cerebral arteries leads to massive and persisting inflammatory reaction contributing to the nearby neuronal damage. Targeting the detrimental pathways of neuroinflammation has been suggested to be beneficial in conditions of ischemic stroke. Nuclear receptor 4A-family (NR4A) member Nurr1 has been shown to be a potent modulator of harmful inflammatory reactions, yet the role of Nurr1 in cerebral stroke remains unknown. Here we show for the first time that an agonist for the dimeric transcription factor Nurr1/retinoid X receptor (RXR), HX600, reduces microglia expressed proinflammatory mediators and prevents inflammation induced neuronal death in in vitro co-culture model of neurons and microglia. Importantly, HX600 was protective in a mouse model of permanent middle cerebral artery occlusion and alleviated the stroke induced motor deficits. Along with the anti-inflammatory capacity of HX600 in vitro, treatment of ischemic mice with HX600 reduced ischemia induced Iba-1, p38 and TREM2 immunoreactivities, protected endogenous microglia from ischemia induced death and prevented leukocyte infiltration. These anti-inflammatory functions were associated with reduced levels of brain lysophosphatidylcholines (lysoPCs) and acylcarnitines, metabolites related to proinflammatory events. These data demonstrate that HX600 driven Nurr1 activation is beneficial in ischemic stroke and propose that targeting Nurr1 is a novel candidate for conditions involving neuroinflammatory component.

Light scattering properties of self-organized nanostructured substrates for thin-film solar cells.

We investigate the scattering properties of novel kinds of nano-textured substrates, fabricated in a self-organized fashion by defocused ion beam sputtering. These substrates provide strong and broadband scattering of light and can be useful for applications in thin-film solar cells. In particular, we characterize the transmitted light in terms of haze and angle-resolved scattering, and we compare our results with those obtained for the commonly employed Asahi-U texture. The results indicate that the novel substrate has better scattering properties compared to reference Asahi-U substrates. We observe super-Lambertian light scattering behavior in selected spectral and angular regions due to the peculiar morphology of the nano-textured interface, which combines high aspect ratio pseudo random structures with a one-dimensional periodic pattern. The enhancement of light absorption observed in a prototype thin film semiconductor absorber grown on nano-textured glass with respect to an Asahi-U substrate further confirms the superior light trapping properties of the novel substrate.

B-type natriuretic peptide may predict prognosis in older adults admitted with a diagnosis other than heart failure.

BACKGROUND AND AIMS: The diagnosis of heart failure (HF) in elderly patients is often difficult, due to overlap of typical signs and symptoms with those of comorbidities. B-type Natriuretic Peptide (BNP) predicts diagnosis and prognosis of HF, but little is known on its predictive role of short-term prognosis when admission diagnosis is other than HF. METHODS AND RESULTS: We prospectively recruited 404 consecutive patients (aged≥65 years) hospitalized in the Unit of Internal Medicine, University of Catania, Catania, Italy, with an admission diagnosis other than HF. Clinical examination, laboratory data and BNP were evaluated at the admission. The predictive value of BNP and other variables for in-hospital mortality, thirty-day mortality and three month re-hospitalization was assessed. During hospitalization 48 (12%) patients died; by logistic regression analysis, in-hospital mortality was not predicted by BNP>600 pg/ml (OR = 1.36; CI 95% = 0.60-2.80; p = 0.4), while it was by chronic kidney disease (CKD, p < 0.001), WBC count (p < 0.001), immobilization syndrome (p < 0.008) and age (p = 0.012). After discharge, 54 patients (15%) died within 30 days; in these patients thirty-day mortality was significantly predicted by BNP>600 pg/ml (OR = 2.70; CI 95% = 1.40-5.00; p = 0.001), CKD (p < 0.001), malnutrition (p = 0.029) and age (p = 0.033). Re-hospitalized patients were 97 (32%); three month re-hospitalization was predicted by BNP>600 pg/ml (OR = 12.28; CI 95% = 6.00-24.90; p < 0.001) and anamnestic HF (p = 0.002). CONCLUSIONS: Our study shows that BNP>600 pg/ml, CKD, malnutrition and age predict thirty-day mortality after discharge in elderly patients with an admission diagnosis other than HF, while CKD, WBC count, immobilization syndrome and age predict in-hospital mortality. Three-month re-hospitalization was predicted by BNP>600 pg/ml and anamnestic HF.

Growth hormone treatment improves final height and nutritional status of children with chronic kidney disease and growth deceleration.

PURPOSE: Growth retardation is a common complication of chronic kidney disease (CKD) in children. Treatment with recombinant human growth hormone (rhGH) has been used to help short children with CKD to attain a height more in keeping with their age group, but the scientific evidence regarding the effect of rhGH on final height is scarce. METHODS: Final heights of children with CKD receiving rhGH treatment (cases) were compared with final heights of a matched cohort of children with CKD that did not receive rhGH therapy (controls). RESULTS: Sixty-eight rhGH-treated cases (44 boys) were compared with 92 untreated controls (60 boys). Mean duration of rhGH therapy was 4.2 ± 0.9 years; rhGH dose was 0.3 ± 0.07 mg/kg/week. Height SDS at baseline was lower in rhGH-treated patients than in controls (-2.00 ± 1.02 versus -0.96 ± 1.11, p < 0.001). Baseline height SDS was significantly lower than target height SDS in both groups. Height SDS significantly improved from baseline to final height attainment in rhGH-treated patients, while it slightly decreased in controls (mean SDS variation 0.69 ± 1.05 in rhGH-treated cases versus -0.15 ± 1.2 in controls). Final height SDS was -1.25 ± 1.06 in rhGH-treated cases and -1.06 ± 1.17 in controls (p = 0.29). Target adjusted final height SDS was -0.91 ± 1.03 in rhGH-treated cases and -0.61 ± 1.17 in controls (p = 0.1). CONCLUSIONS: Long-term rhGH therapy is able to reduce the linear growth deceleration of children with CKD, and ultimately to improve their final height, reducing the difference with target height.

Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes.

BACKGROUND: Array-comparative genomic hybridization (array-CGH) is a widely used technique to detect copy number variants (CNVs) associated with developmental delay/intellectual disability (DD/ID). AIMS: Identification of genomic disorders in DD/ID. MATERIALS AND METHODS: We performed a comprehensive array-CGH investigation of 1,015 consecutive cases with DD/ID and combined literature mining, genetic evidence, evolutionary constraint scores, and functional information in order to assess the pathogenicity of the CNVs. RESULTS: We identified non-benign CNVs in 29% of patients. Amongst the pathogenic variants (11%), detected with a yield consistent with the literature, we found rare genomic disorders and CNVs spanning known disease genes. We further identified and discussed 51 cases with likely pathogenic CNVs spanning novel candidate genes, including genes encoding synaptic components and/or proteins involved in corticogenesis. Additionally, we identified two deletions spanning potential Topological Associated Domain (TAD) boundaries probably affecting the regulatory landscape. DISCUSSION AND CONCLUSION: We show how phenotypic and genetic analyses of array-CGH data allow unraveling complex cases, identifying rare disease genes, and revealing unexpected position effects.

Metronomic chemotherapy with oral vinorelbine (mVNR) and capecitabine (mCAPE) in advanced HER2-negative breast cancer patients: is it a way to optimize disease control? Final results of the VICTOR-2 study.

PURPOSE: The VICTOR-1 study demonstrated that the all-oral metronomic combination of vinorelbine and capecitabine is highly active and well tolerated in hormone receptor-positive/HER2-negative patients. The VICTOR-2 study was designed to confirm these results. METHODS: Patients received mVNR 40 mg three times a week and mCAPE 500 mg three times a day, continuously. The primary endpoint was the clinical benefit rate (CBR); secondary endpoints were toxicity, objective response rate (ORR), and progression-free survival (PFS). RESULTS: Eighty patients were evaluable for the primary efficacy analysis. Median age was 65.3 years; most patients had HR-positive tumors (65 %). The CBR was 45.7 % (95 % CI 28.8-63.4) and 51.1 % (95 % CI 35.8-66.3) in first- and ≥ second-line therapy, respectively. The ORR was 35.5 % in first-line (95 % CI 19.2-54.6) and 25.6 % in ≥second-line (95 % CI 13.5-41.2). The median duration of response was 11.3 and 6.4 months and PFS rates at 1 year were 24.3 and 22.2 %, respectively. In triple-negative breast cancer patients (N = 28, 35 %) a lower, but clinically relevant CBR (35.7, 95 % CI 18.6-55.9) was observed. The main toxicities per cycle were non-febrile neutropenia (1.1 %), hand-foot syndrome (1.0 %), nausea and vomiting (1.0 %), leucopenia (0.8 %), fatigue (0.7 %), and diarrhea (0.4 %). CONCLUSION: The VICTOR-2 study confirms the clinical activity of mVNR and mCAPE in HER2-negative breast cancer patients, suggesting that the easy schedule of administration, which requires monthly blood tests and limits patients' dependence on hospitals, and the low cost of the drugs are valuable elements, even for countries with limited access to innovative or expensive drugs.

Desiccating stress-induced disruption of ocular surface immune tolerance drives dry eye disease.

Dry eye is an allegedly autoimmune disorder for which the initiating mechanisms and the targeted antigens in the ocular surface are not known, yet there is extensive evidence that a localized T helper type 1 (Th1)/Th17 effector T cell response is responsible for its pathogenesis. In this work, we explore the reconciling hypothesis that desiccating stress, which is usually considered an exacerbating factor, could actually be sufficient to skew the ocular surface's mucosal response to any antigen and therefore drive the disease. Using a mouse model of dry eye, we found that desiccating stress causes a nuclear factor kappa B (NF-κB)- and time-dependent disruption of the ocular surface's immune tolerance to exogenous ovalbumin. This pathogenic event is mediated by increased Th1 and Th17 T cells and reduced regulatory T cells in the draining lymph nodes. Conversely, topical NF-κB inhibitors reduced corneal epithelial damage and interleukin (IL)-1ß and IL-6 levels in the ocular surface of mice under desiccating stress. The observed effect was mediated by an augmented regulatory T cell response, a finding that highlights the role of mucosal tolerance disruption in dry eye pathogenesis. Remarkably, the NF-κB pathway is also involved in mucosal tolerance disruption in other ocular surface disorders. Together, these results suggest that targeting of mucosal NF-κB activation could have therapeutic potential in dry eye.

Adhesion modification of neural stem cells induced by nanoscale ripple patterns.

We have studied the influence of anisotropic nanopatterns (ripples) on the adhesion and morphology of mouse neural stem cells (C17.2) on glass substrates using cell viability assay, optical microscopy and atomic force microscopy. The ripples were produced by defocused ion beam sputtering with inert Ar ions, which physically remove atoms from the surface at the energy of 800 eV. The ripple periodicity (∼200 nm) is comparable to the thickness of the cytoplasmatic microspikes (filopodia) which link the stem cells to the substrate. All methods show that the cell adhesion is significantly lowered compared to the same type of cells on flat glass surfaces. Furthermore, the AFM analysis reveals that the filopodia tend to be trapped parallel or perpendicular to the ripples, which limits the spreading of the stem cell on the rippled substrate. This opens the perspective of controlling the micro-adhesion of stem cells and the orientation of their filopodia by tuning the anisotropic substrate morphology without chemical reactions occurring at the surface.

A 5.8 Mb interstitial deletion on chromosome Xq21.1 in a boy with intellectual disability, cleft palate, hearing impairment and combined growth hormone deficiency.

BACKGROUND: Deletions of the long arm of chromosome X in males are a rare cause of X-linked intellectual disability. Here we describe a patient with an interstitial deletion of the Xq21.1 chromosome. CASE PRESENTATION: In a 15 year boy, showing intellectual disability, short stature, hearing loss and dysmorphic facial features, a deletion at Xq21.1 was identified by array-CGH. This maternally inherited 5.8 Mb rearrangement encompasses 14 genes, including BRWD3 (involved in X-linked intellectual disability), TBX22 (a gene whose alterations have been related to the presence of cleft palate), POU3F4 (mutated in X-linked deafness) and ITM2A (a gene involved in cartilage development). CONCLUSION: Correlation between the clinical findings and the function of gene mapping within the deleted region confirms the causative role of this microrearrangement in our patient and provides new insight into a gene possibly involved in short stature.

Tracking novel adenovirus in environmental and human clinical samples: no evidence of endemic human adenovirus type 58 circulation in Córdoba city, Argentina.

In recent years, several types of human adenovirus (HAdV) have arisen from the recombination between two or more previously known HAdV types, but their epidemiology is poorly understood. In this study, we investigated the circulation of HAdV-58, a recently described HAdV isolated from an HIV-positive patient in Córdoba city, Argentina. For this purpose, a 30-month survey was conducted to study the presence of this type of adenovirus in sewage samples collected at the inlet from a wastewater treatment plant in Córdoba city, Argentina. Complementarily, the virus was sought in stools of HIV-positive patients. Although HAdVs were detected in human stool samples and in a high percentage of sewage samples, no evidence of HAdV-58 circulation was detected. We suggest that there is no endemic circulation of HAdV-58 in the geographical local area. The trend is that the number of identified HAdVs increases over time. In this context, understanding the current circulating HAdVs may be biologically relevant.

Sex-specific effects of prenatal and postnatal nutritional conditions on the oxidative status of great tit nestlings.

The early life period is characterized by fast growth and development, which can lead to high reactive oxygen species (ROS) production. Young animals thus have to balance their investment in growth versus ROS defence, and this balance is likely mediated by resource availability. Consequently resources transferred prenatally by the mother and nutritional conditions experienced shortly after birth may crucially determine the oxidative status of young animals. Here, we experimentally investigated the relative importance of pre- and early postnatal nutritional conditions on the oxidative status of great tit nestlings (Parus major). We show that resources transferred by the mother through the egg and nutritional conditions encountered after hatching affect the oxidative status of nestling in a sex-specific way. Daughters of non-supplemented mothers and daughters which did not receive extra food during the early postnatal period had higher oxidative damage than sons, while no differences between sons and daughters were found when extra food was provided pre- or postnatally. No effect of the food supplementations on growth, fledging mass or tarsus length was observed, indicating that female nestlings maintained their investment in growth at the expense of ROS defence mechanisms when resources were limited. The lower priority of the antioxidant defence system for female nestlings was also evidenced by lower levels of specific antioxidant components. These results highlight the important role of early parental effects in shaping oxidative stress in the offspring, and show that the sensitivity to these parental effects is sex-specific.

Rotavirus seasonality in urban sewage from Argentina: effect of meteorological variables on the viral load and the genetic diversity.

In Argentina, the rotavirus disease exhibits seasonal variations, being most prevalent in the fall and winter months. To deepen the understanding of rotavirus seasonality in our community, the influence of meteorological factors on the rotavirus load and the genetic diversity in urban raw sewage from Córdoba city, Argentina were evaluated. Wastewater samples were collected monthly during a three-year study period and viral particles were concentrated by polyethylene glycol precipitation. RT-nested PCR was applied for rotavirus detection, and VP7/VP4 characterization and real-time PCR for rotavirus quantification. Both molecular techniques showed relatively similar sensitivity rates and revealed rotavirus presence in urban wastewater in cold and warm seasons, indicating its circulation in the local community all year round. However, a slight trend for rotavirus circulation was noted by real-time PCR in the fall and winter seasons, showing a significantly higher peak of rotavirus concentration at mean temperatures lower than 18°C and also higher, although not statistically different during drier weather. VP7 and VP4 gene characterization showed that G1 and P[8] genotypes were dominant, and temporal variations in genotype distribution were not observed. Rotavirus spread is complex and our results point out that weather factors alone cannot explain the seasonal quantitative pattern of the rotavirus disease. Therefore, alternative transmission routes, changes in human behavior and susceptibility, and the stability and survivability of the virus might all together contribute to the seasonality of rotavirus. The results obtained here provide evidence regarding the dynamics of rotavirus circulation and maintenance in Argentina.

Persistence of measles neutralizing antibody related to vaccine and natural infection acquired before HIV infection.

Little is known about long-lasting measles protective immunity when exposure to wild-type or vaccine measles virus precedes HIV infection. The results obtained suggest that measles immunity wanes and the lowest measles geometric mean titres (GMT) were significantly associated with measles vaccine-induced immunity in individuals that later developed HIV infection (86% prevalence, GMT 164 mIU/ml) compared to naturally induced immunity in HIV-infected adults (100% prevalence, GMT 340 mIU/ml, P = 0·0082) or non-HIV infected adults (100%, GMT 724 mIU/ml, P = 0·0001), and vaccine-induced immunity in non-HIV-infected adults (100%, GMT 347 mIU/ml, P = 0·017). The study was conducted in an area without wild-type virus circulation since 2000. The absence of virus circulating may alter the paradigm of lifelong immunity to measles virus after vaccination. As the proportion of HIV-infected individuals possessing only vaccine-induced immunity continues to grow, checking the status of measles immunity in this group is strongly recommended.

Monoclonal gammopathy of undetermined significance in pediatric kidney transplant: a possible role of Epstein-Barr virus.

MG is a common event of hematologic malignancies. There are many papers regarding kidney transplantation patients with MGUS in adults, while data in pediatrics are scarce. The etiology and clinical significance of MGUS are unclear both in adults and children. Immunosuppressive drugs, graft antigenicity, and viral infection could play a possible role. The viruses most frequently implicated seem to be EBV or CMV in particular, but their role has to be defined better. However, many investigators have emphasized an impaired balance between an adequate immune response and reactivation of viral infection.

Ureteral or vesical involvement in Henoch-Schönlein syndrome: a systematic review of the literature.

BACKGROUND: Little information is available on ureteral or vesical involvement in Henoch-Schönlein syndrome. To determine the features of this condition we performed a formal analysis of peer-reviewed scientific literature on this topic. METHODS: The US National Library of Medicine database was used as the data source. All articles published as full-length articles or letters were collected. Reports published in languages other than English, French, German, Italian or Spanish were not considered. RESULTS: We analyzed 32 reports describing 35 cases (24 male and 11 female subjects aged between 3.5 and 63, median 7.0 years) with ureteral (n = 30), vesical (n = 4), or both ureteral and vesical involvement (n = 1). The presentation included colicky abdominal pain, macroscopic hematuria (sometimes containing blood clots), urinary tract infection or urinary retention. The diagnosis of ureteral involvement was often fortuitous. Patients with vesical involvement were managed conservatively. However, the majority of those with ureteral involvement were managed surgically. CONCLUSIONS: Ureteral or vesical involvement is unusual and likely underappreciated in Henoch-Schönlein syndrome. Improved recognition and wider appreciation of this involvement can help to avoid associated morbidity. Management must be individualized for each patient. A multidisciplinary approach may be of value in planning medical treatment, surgical intervention, and follow-up.

TRAbectedin in adVanced rEtroperitoneal well differentiated/dedifferentiated Liposarcoma and Leiomyosarcoma (TRAVELL): results of a phase II study from the Italian Sarcoma Group.

BACKGROUND: This is a multicentre, single-arm, phase II study aimed at further exploring the activity of trabectedin as second-/further-line treatment in retroperitoneal leiomyosarcoma (LMS) and well-differentiated/dedifferentiated liposarcoma (LPS). MATERIALS AND METHODS: The primary endpoint was the growth modulation index (GMI) defined as the ratio between PFS under trabectedin (PFS) and during previous chemotherapy treatment: time to progression (TTP-1). Secondary endpoints were objective response rate (ORR) and PFS. As per protocol, patients were considered responders if the GMI was >1.33, non-responders if <0.75 and neither if 0.76-1.32. RESULTS: Overall 91 patients were assessable for the primary endpoint (32 patients with LMS and 59 patients with LPS): the median number of cycles received was 6.0 (Q1-Q3 3.0-12.0), and the main reason for treatment discontinuation was disease progression in 72% of patients. The median PFS was 6.0 months, while the median TTP1 was 7.5 months (8.1 and 6.4 months for LMS and LPS, respectively). Thirty-three patients [52%, 95% confidence interval (CI) 36% to 58%, P = 0.674, odds of response 1.1] had a GMI >1.33 (LMS 46%, 95% CI 26% to 67%, odds of response 0.85; LPS 56%, 95% CI 40% to 72%, odds of response 1.3). Overall, in LPS we observed 15/47 patients with a GMI <0.5 and 15/47 patients with a GMI >2. Among LMS patients, 9/26 had a GMI <0.5 and 10/26 had a GMI >2. Overall, ORR (complete response + partial response) was 16% (24% for LMS and 12% for LPS). CONCLUSIONS: While the primary endpoint of the study was not met, we noticed a subgroup of patients with a markedly discrepant TTP with trabectedin in comparison to previous therapy (GMI <0.5 or >2, the latter including some patients with a long TTP with trabectedin). A mismatch between PFS and overall survival was observed, possibly due to the natural history of the two different histologies and the availability of further lines in LMS.