Laboratory findings in psoriatic arthritis.

Psoriatic arthritis (PsA) has been classically defined as an inflammatory arthritis associated with psoriasis. However, in comparison with other relevant inflammatory arthropathies, in which a definite diagnosis is frequently possible only by means of laboratory investigations, in PsA true laboratory diagnostic markers are lacking. Some markers are utilised more to differentiate other diseases than to characterise PsA. For example in polyarticular PsA, which may be in some cases indistinguishable from RA, the rheumatoid factor (RF) or the more specific and recently introduced antibodies to cyclic citrullinated peptides (anti-CCP), may be useful to better identify RA. However, RF was found in 5% to 13% of patients with PsA, and anti-CCP may be observed in almost similar percentage. The determination of ESR and/or CRP is frequently disappointing in PsA, since they are both elevated in only half of the patients with PsA. However, ESR and/or CRP are included in the most utilised response criteria for RA, such as ACR and DAS, and, in addition are also considered reliable in the assessment of PsA. Furthermore, elevated levels of ESR have been proposed as one of the best predictors of damage progression and, in addition, a low ESR seems protective, while an ESR >15 mm/h is one of the factors associated with an increased mortality in PsA. The synovial fluid (SF) effusion is much higher in PsA, in comparison with other arthropathies. When available, SF analysis may offer additive information useful for the diagnosis, such as the increased number of leukocytes, which underlines the inflammatory nature of the effusion even in a patient with normal serum levels of acute phase response. We found that elevated IL-1 levels in SF of patients with early disease (<6 months), may be predictive of an evolution in polyarticular form at follow-up. This observation is in keeping with the crucial role that inflammatory cytokines play in PsA, probably related to a genetic predisposition. The recent introduction in PsA of anti-TNF-α agents and the demonstration of their efficacy in the management of many clinical disease expressions including peripheral arthropathy, axial involvement, enthesopathy and skin manifestations, have stimulated the research also in the field of the possible laboratory markers. Key words: Psoriatic arthritis, laboratory investigations arthriti

Molecular detection of Cyclospora in water, soil, vegetables and humans in southern Italy signals a need for improved monitoring by health authorities

To date, in Europe, there is scant information on the occurrence of Cyclospora in water from treatment plants and in humans, and no data are available on soil or fresh plant products. Here, we undertook the first molecular survey of Cyclospora in multiple biological matrices collected from the Apulia region of southern Italy. Samples of irrigation water from four municipal treatment plants, eight different types of vegetables or fruit (cucumber, lettuce, fennel, celery, tomato, melon, endive and chicory) and soil from the same farms on which these plants were grown, as well as faecal samples from humans living in the same region were tested by qPCR-coupled single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. Cyclospora was detected in 15.5% of all 213 samples tested. Specifically, this protist was detected in (i) treated water (21.3% of 94 samples), well water (6.2% of 16), but not drinking water (0% of 3); (ii) soil (11.8% of 51 samples) and vegetables (12.2% of 49),with the highest prevalence (18.7%) on fennel; and (iii) human stools (27.5% of 40 samples). In environmental and food samples, Cyclosporawas detectedmainly in autumn and was significantly more prevalent in the faeces from humans of 40–50 years of age. This is the first comprehensive molecular survey of Cyclospora in environmental, food and human faecal samples in Europe. These data suggest that irrigation water, soil and vegetables might be contaminated by Cyclospora cayetanensis, which might represent a source of infection to humans in the study area and calls for monitoring by health authorities

Sibling relationships and family functioning in siblings of early adolescents, adolescents and young adults with autism spectrum disorder

The purpose of the study was to investigate how family functioning (defined as the ability that family members hold to manage stressful events, and intimate and social relationships), the degree to which family members feel happy and fulfilled with each other (called family satisfaction), and the demographical characteristics of siblings (age and gender) impacted on sibling relationships. The Circumplex Model of Marital and Family Systems and Behavioral Systems constituted the theoretical frameworks that guided our study. Eighty-six typically developing adolescents and young adults having a sister or a brother with autism spectrum disorder were enrolled. Results indicated that the youngest age group (early adolescents) reported to engage more frequently in negative behaviors with their siblings with ASD than the two older age groups (middle adolescents and young adults). No significant differences were found among the three age groups regarding behaviors derived from attachment, caregiving and affiliative systems. Family satisfaction and age significantly predicted behaviors during sibling interactions. Suggestions on prevention and intervention programs were discussed in order to prevent parentification among typically developing siblings and decrease episodes of quarrels and overt conflicts between brothers and sisters with and without AS

Giardia and Cryptosporidium in inflowing water and harvested shellfish in a Lagoon in Southern Italy

Giardia and Cryptosporidium spp. are important enteric protozoan pathogens for humans and animals, and have been found to contaminate water as well as edible shellfish all over the world. This is the first study to simultaneously investigate the presence of Giardia and Cryptosporidium in inflowing water and harvested shellfish in a geographically closed environment (Varano Lagoon, Southern Italy). Samples of treated wastewater were collected each month - at the outlet from the treatment plant, and downstream at the inlet into the lagoon - from the channels flowing into the Lagoon, together with specimens of Ruditapes decussatus and Mytilus galloprovincialis from shellfish-farms on the same lagoon. Giardia cysts were found by immunofluorescence (IF) microscopy in 16 out of 21 samples of treated wastewater and in 7 out of 21 samples from downstream water channels, and viable cysts were also detected by a beta-giardin RT-PCR. G. duodenalis Assemblages A and B were identified by small ribosomal Subunit (18S-rDNA) and triosephosphate isomerase (tpi)-PCR, followed by sequencing. Cryptosporidium oocysts were found by IF in 5 out of 21 wastewater samples, and in 8 out of 21 samples from water channels. Molecular analysis identified the zoonotic species Cryptosporidium parvum by oocyst wall protein (COWP)-PCR and sequencing. Higher concentrations of Giardia cysts than Cryptosporidium oocysts were registered in almost all wastewater and water samples. IF and molecular testing of shellfish gave negative results for both protozoa. Wastewaters carrying Giardia and Cryptosporidium (oo)cysts are discharged into the Lagoon; however, the shellfish harvested in the same environment were found to be unaffected, thus suggesting that physical, ecological and climatic conditions may prevent contamination of harvested shellfish. (C) 2008 Published by Elsevier Ireland Ltd

Role of dutasteride in pre‐clinical ETS fusion‐positive prostate cancer models

BACKGROUND Androgens play a crucial role in prostate cancer, hence the androgenic pathway has become an important target of therapeutic intervention. Previously we discovered that gene fusions between the 5′‐untranslated region of androgen regulated gene TMPRSS2 and the ETS transcription factor family members were present in a majority of the prostate cancer cases. The resulting aberrant overexpression of ETS genes drives tumor progression. METHODS Here, we evaluated the expression levels of 5α‐reductase isoenzymes in prostate cancer cell lines and tissues. We tested the effect of dutasteride, a 5α‐reductase inhibitor, in TMPRSS2–ERG fusion‐positive VCaP cell proliferation and cell invasion. We also evaluated the effect of dutasteride on the TMPRSS2–ERG fusion gene expression. Finally, we tested dutasteride alone or in combination with an anti‐androgen in VCaP cell xenografts tumor model. RESULTS Our data showed that 5α‐reductase SRD5A1 and SRD5A3 isoenzymes that are responsible for the conversion of testosterone to DHT, are highly expressed in metastatic prostate cancer compared to benign and localized prostate cancer. Dutasteride treatment attenuated VCaP cell proliferation and invasion. VCaP cells pre‐treated with dutasteride showed a reduction in ERG and PSA expression. In vivo studies demonstrated that dutasteride in combination with the anti‐androgen bicalutamide significantly decreased tumor burden in VCaP cell xenograft model. CONCLUSIONS Our findings suggest that dutasteride can inhibit ERG fusion‐positive cell growth and in combination with anti‐androgen, significantly reduce the tumor burden. Our study suggests that anti‐androgens used in combination with dutasteride could synergistically augment the therapeutic efficacy in the treatment of ETS‐positive prostate cancer. Prostate 72:1542–1549, 2012. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93574/1/22509_ftp.pd

Productivity of energy sorghum irrigated with reclaimed wastewaters

The sustainability of biomass sorghum ( Sorghum bicolor L. Moench.) in the Mediterranean environment is linked to the possibility of increasing crop productivity by using conventional clean water and wastewater irrigation. An experimental setup was arranged in Southern Italy during 2012 and 2013 seasons to determine the potential productivity of biomass sorghum irrigated with conventional water at different irrigation regimes (100 and 50% of calculated evapotranspiration) and different types of municipal wastewater. During the sorghum growing season, the crop development (biomass and leaf are index) and the soil water content were monitored for all irrigation treatments. The data obtained showed that the dry biomass of sorghum irrigated with the deficit treatment (17 t ha –1 ) was lower compared with conventionally irrigated sorghum. For both seasons and under full irrigated conditions, sorghum irrigated with wastewater produced on average more dry biomass (23 t ha –1 ) than the crop irrigated with conventional water (20.5 t ha –1 ), using the same irrigation volumes

Bioenergy productivity of sugar beet irrigated with reclaimed wastewaters

The use of treated wastewater to irrigate the sugar beet (Beta Vulgaris L. var. saccharifera) for bioethanol could play a strategic role to contrast the use of natural water resources and increase the productivity of the crop. The 2-year experiment (2013-2014) was performed on sugar beet irrigated with fresh water and wastewater at different steps of the reclamation process (secondary and tertiary treatments). The data obtained showed that the root sugar beet yield and ethanol production under fresh water treatment (52.2 Mg ha–1 and 5446 L ha–1) were lower respect to that obtained from the secondary and tertiary wastewater treatments (66.7 Mg ha–1 and 6785 L ha–1, and 58.7 Mg h–1 and 6164 L ha–1, respectively), with the same irrigation volumes. These results can depend on the higher quantity of nutrient uptake when wastewater is used for irrigation. In particular, the average N applied (as nitrate and ammonium) with irrigation during the growing seasons (2013 and 2014) was corresponding to the supply of 4, 28 and 20 kg ha–1, for the fresh water, secondary, and tertiary wastewater treatments, respectively

Maternal neurofascin-specific autoantibodies bind to structures of the fetal nervous system during pregnancy, but have no long term effect on development in the rat

Neurofascin was recently reported as a target for axopathic autoantibodies in patients with multiple sclerosis (MS), a response that will exacerbate axonal pathology and disease severity in an animal model of multiple sclerosis. As transplacental transfer of maternal autoantibodies can permanently damage the developing nervous system we investigated whether intrauterine exposure to this neurofascin-specific response had any detrimental effect on white matter tract development. To address this question we intravenously injected pregnant rats with either a pathogenic anti-neurofascin monoclonal antibody or an appropriate isotype control on days 15 and 18 of pregnancy, respectively, to mimic the physiological concentration of maternal antibodies in the circulation of the fetus towards the end of pregnancy. Pups were monitored daily with respect to litter size, birth weight, growth and motor development. Histological studies were performed on E20 embryos and pups sacrificed on days 2, 10, 21, 32 and 45 days post partum. Results: Immunohistochemistry for light and confocal microscopy confirmed passively transferred anti-neurofascin antibody had crossed the placenta to bind to distinct structures in the developing cortex and cerebellum. However, this did not result in any significant differences in litter size, birth weight, or general physical development between litters from control mothers or those treated with the neurofascin-specific antibody. Histological analysis also failed to identify any neuronal or white matter tract abnormalities induced by the neurofascin-specific antibody. Conclusions: We show that transplacental transfer of circulating anti-neurofascin antibodies can occur and targets specific structures in the CNS of the developing fetus. However, this did not result in any pre- or post-natal abnormalities in the offspring of the treated mothers. These results assure that even if anti-neurofascin responses are detected in pregnant women with multiple sclerosis these are unlikely to have a negative effect on their children

Rapid, ultra low coverage copy number profiling of cell-free DNA as a precision oncology screening strategy.

Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling. We applied PRINCe to a retrospective cohort of 124 cfDNA samples from 100 patients with advanced cancers, including 76 men with metastatic castration-resistant prostate cancer (mCRPC), enabling cfDNA tumor content approximation and actionable focal CNA detection, while facilitating concordance analyses between cfDNA and tissue-based NGS profiles and assessment of cfDNA alteration associations with mCRPC treatment outcomes. Therapeutically relevant focal CNAs were present in 42 (34%) cfDNA samples, including 36 of 93 (39%) mCRPC patient samples harboring AR amplification. PRINCe identified pre-treatment cfDNA CNA profiles facilitating disease monitoring. Combining PRINCe with routine targeted NGS of cfDNA enabled mutation and CNA assessment with coverages tuned to cfDNA tumor content. In mCRPC, genome-wide PRINCe cfDNA and matched tissue CNA profiles showed high concordance (median Pearson correlation = 0.87), and PRINCe detectable AR amplifications predicted reduced time on therapy, independent of therapy type (Kaplan-Meier log-rank test, chi-square = 24.9, p &lt; 0.0001). Our screening approach enables robust, broadly applicable cfDNA-based precision oncology for patients with advanced cancer through scalable identification of therapeutically relevant CNAs and pre-/post-treatment genomic profiles, enabling cfDNA- or tissue-based precision oncology workflow optimization