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Well-established criteria for evaluating the response to treatment and the appropriate follow-up of individual patients are critical in clinical oncology. The current evidence-based data on these issues in terms of the management of gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are unfortunately limited. This document by the Italian Association of Clinical Endocrinologists (AME) on the criteria for the follow-up of GEP-NEN patients is aimed at providing comprehensive recommendations for everyday clinical practice based on both the best available evidence and the combined opinion of an interdisciplinary panel of experts. The initial risk stratification of patients with NENs should be performed according to the grading, staging and functional status of the neoplasm and the presence of an inherited syndrome. The evaluation of response to the initial treatment, and to the subsequent therapies for disease progression or recurrence, should be based on a cost-effective, risk-effective and timely use of the appropriate diagnostic resources. A multidisciplinary evaluation of the response to the treatment is strongly recommended and, at every step in the follow-up, it is mandatory to assess the disease state and the patient performance status, comorbidities, and recent clinical evolution. Local expertise, available technical resources and the patient preferences should always be evaluated while planning the individual clinical management of GEP-NENs.

Babesia caballi and Theileria equi are tick-borne pathogens causing equine piroplasmosis infecting the Equidae family in which they cause significant sanitary and economic losses. Furthermore, equine piroplasmosis is included in the World Animal Health Organization (OIE) notifiable diseases list with possible movement restrictions for positive horses. Thirty-nine EDTA and whole-blood samples collected during 2013 and 2014 from symptomatic and asymptomatic horses of Central-Southern Italy were included in the present study either because of their strongly positive results in Real Time (RT) PCRs targeting the 18S rRNA gene specific for each piroplasm and/or due to their serological ELISA/18S rRNA RT-PCR discordant results. A nested PCR amplifying the hypervariable V4 region of the 18S rRNA gene of both piroplasms was performed on all samples. T. equi positive samples were also analysed with a PCR targeting the equi merozoite antigen 1-gene (EMA-1). The sequences obtained were thirty for T. equi, 25 of which were for the hypervariable V4 region of the 18S rRNA gene and 13 for the EMA-1 gene, with eight samples positive for both targets, while only six 18S rRNA gene sequences were retrieved for B. caballi. The phylogenetic analysis results are as follows: T. equi sequences of the 18S rRNA gene clustered in three different phylogenetic groups, respectively in the A (15), B (9) and C (1) while those of B. caballi in the A (1), B1 (3) and B2 (2) groups. T. equi sequences for EMA-1 gene clustered in A (11) and in B (2). This analysis confirms that both T. equi and B. caballi sequences present a genetic heterogeneity independently of their geographical location, similar to that reported by other authors. Statistical associations were evaluated between phylogenetic groups of T. equi 18S rRNA gene and each of the following variables, using Fisher's exact test: clinical signs, serological ELISA/18S rRNA RT-PCR discordant results and T. equi EMA-1 negativity. The different groups were found to be statistically related to the presence of signs (less present in group B samples), to ELISA negativity/18S rRNA RT-PCR positivity (more seronegative samples in group B). No statistical analysis was performed for the B. caballi as the number of sequences available was insufficient and for the EMA −1 sequences which almost all grouped in the same cluster. The results here obtained provide additional information about T. equi and B. caballi sequences, which could also be used to verify the performance of serological and molecular diagnostic methods.

Background: Several meta-analyses have identified methodological limitations in female stress urinary incontinence (SUI) trials, precluding the synthesis of primary studies and high-quality evidence. Objectives: Evaluation of outcome measure selection and outcome reporting in randomised controlled trials (RCTs) on surgery for SUI. Search strategy: Systematic review of RCTs identified from bibliographical databases, including Medline, Cochrane, and EMBASE. Selection criteria: Randomised controlled trials evaluating the efficacy and safety of surgical interventions for the management of female SUI. Data collection and analysis: Two researchers independently assessed the included studies and documented outcomes. Main results: Overall, 108 studies were identified that included 422 reported outcomes and 119 outcome measures. The three most common outcomes were cure rates (87 studies), quality of life (85 studies), and overactive bladder (78 studies). The median methodological quality rating was 3 (range 0–3) and the outcome reporting quality rating was 3 (range 0–5). Multinomial logistic regression analysis revealed that the methodological quality and use of validated questionnaire were significant predictors of the quality of outcome reporting (β = 0.538, P

Summary Background Mutations in LRRK2 , the gene that encodes leucine-rich repeat kinase 2, are a cause of Parkinson's disease (PD). The International LRRK2 Consortium was established to answer three key clinical questions: can LRRK2 -associated PD be distinguished from idiopathic PD; which mutations in LRRK2 are pathogenic; and what is the age-specific cumulative risk of PD for individuals who inherit or are at risk of inheriting a deleterious mutation in LRRK2 ? Methods Researchers from 21 centres across the world collaborated on this study. The frequency of the common LRRK2 Gly2019Ser mutation was estimated on the basis of data from 24 populations worldwide, and the penetrance of the mutation was defined in 1045 people with mutations in LRRK2 from 133 families. The LRRK2 phenotype was defined on the basis of 59 motor and non-motor symptoms in 356 patients with LRRK2 -associated PD and compared with the symptoms of 543 patients with pathologically proven idiopathic PD. Findings Six mutations met the consortium's criteria for being proven pathogenic. The frequency of the common LRRK2 Gly2019Ser mutation was 1% of patients with sporadic PD and 4% of patients with hereditary PD; the frequency was highest in the middle east and higher in southern Europe than in northern Europe. The risk of PD for a person who inherits the LRRK2 Gly2019Ser mutation was 28% at age 59 years, 51% at 69 years, and 74% at 79 years. The motor symptoms (eg, disease severity, rate of progression, occurrence of falls, and dyskinesia) and non-motor symptoms (eg, cognition and olfaction) of LRRK2 -associated PD were more benign than those of idiopathic PD. Interpretation Mutations in LRRK2 are a clinically relevant cause of PD that merit testing in patients with hereditary PD and in subgroups of patients with PD. However, this knowledge should be applied with caution in the diagnosis and counselling of patients. Funding UK Medical Research Council; UK Parkinson's Disease Society; UK Brain Research Trust; Internationaal Parkinson Fonds; Volkswagen Foundation; National Institutes of Health: National Institute of Neurological Disorders and Stroke and National Institute of Aging; Udall Parkinson's Disease Centre of Excellence; Pacific Alzheimer Research Foundation Centre; Italian Telethon Foundation; Fondazione Grigioni per il Morbo di Parkinson; Michael J Fox Foundation for Parkinson's Research; Safra Global Genetics Consortium; US Department of Veterans Affairs; French Agence Nationale de la Recherche.

SUMMARY – The expression of HIF-1a and HSF1 was investigated in plasma samples (T0: at birth; T12: 12 hours after birth) of 9 neonates (4 healthy and 5 sick foals); plasma MDA concentration was also evaluated in 16 neonates (10 healthy and 6 sick foals). MDA concentration, HIF-1a and HSF1 expression decreased significantly at T12 if compared with T0 (p< 0.05). HIF-1a was significantly higher in sick foals at all sampling times (p< 0.05) and resulted correlated to pCO2 at T0 and to MDA at T12 (p< 0,05; R=0,83 e R=-0,72, respectively). HSF was significantly correlated to HCT and RBC at T0 (p< 0,05; R=0,68 e R=0,77, respectively). The parameters measured could be considered potential indexes of perinatal hypoxia.

We report the results of a prospective Italian multi-center study of the effects of lanreotide, a slow-release somatostatin analog, on left ventricular morphology and function and on the prevalence of ventricular arrhythmic events in 19 patients with active, newly diagnosed, uncomplicated acromegaly. Cardiac features were evaluated with Doppler-echocardiography and 24-h Holter ECG monitoring at baseline and after 6 months of lanreotide therapy. Fifteen patients (78.9%) had left ventricular hypertrophy. Lanreotide treatment significantly decreased the left ventricular mass (127.8+/-6.9 vs 140.7+/-7.1 g/m2, p0.001) and left ventricular hypertrophy significantly disappeared in 6 of these patients. Treatment did not significantly affect systolic function, whereas it increased the Doppler-derived early-to-late mitral flow velocity, (E/A) ratio, of early-to-late trans-mitral flow velocity (1.34+/-0.1 vs 1.09+/-0.06, p=0.001). Stroke volume was slightly but not significantly increased after treatment, whereas systolic BP was significantly higher (134+/-14 vs 129+/-13 mmHg, p0.05). The 24-h mean heart rate was significantly reduced after treatment (66.5+/-11 vs 71.5+/-20 beats/min, p0.05). Supra-ventricular premature beats (50/24 h) occurred in 16.6% of patients and were unaffected by treatment. Differently, ventricular premature beats (50/24 h) occurred in 33.3% of patients before treatment vs 16.5%, after treatment. In conclusion, lanreotide reduced the left ventricular mass, and improved ventricular filling and ventricular arrhythmic profile.

The aim of this study was to determine the prevalence of polycystic ovary morphology (PCO) among Nigerian women attending for pelvic ultrasound. This was a retrospective study of the ultrasound scan findings of all women who attended for pelvic ultrasound scan at a new teaching hospital in southern Nigeria from the commencement of ultrasound services on 1 March to 31 July 2010. The main indication for the scans was infertility (52.7%), and the commonest finding was fibroid (44.6%). Polycystic ovary morphology was present in 12.2% of the women. On average women with PCO were younger (30.3 v 35.0 years) and more likely to present with amenorrhea (33.3 v 7.6%) than women without PCO, but there was no other statistically significant differences between the two groups. This study suggests that Nigerian women have a low incidence of PCO morphology. (Afr J Reprod Health 2014; 18[1]: 161-164)Keywords: Prevalence, Polycystic Ovary Morphology, Nigerian

To the Editor: Tsuji and colleagues (July 18 issue)1 report that variants in the gene encoding coenzyme Q2 (COQ2) increase the risk of multiple-system atrophy. They observed homozygous COQ2 variants encoding the substitutions M78V and V343A in a consanguineous Japanese family with multiple-system atrophy subtype P and noted an association between V343A and sporadic multiple-system atrophy (minor-allele frequency [MAF], 4.8% of cases vs. 1.6% of controls; odds ratio, 3.05; 95% confidence interval, 1.65 to 5.85). However, the authors erroneously labeled human COQ2 variability from the fourth ATG start codon in exon 1, which encodes the smallest protein isoform and does not functionally complement the yeast coq2-null mutant.2 On the basis of the National Center for Biotechnology Information (NCBI) Reference Sequence (NM_015697.7), M78V should be labeled COQ2 c.382A→G (p.M128V) and V343A should be labeled c.1178T→C (p.V393A). We sequenced COQ2 in 299 Korean persons with multiple-system atrophy and 365 unaffected Korean persons and observed heterozygous COQ2 c.320G→C (encoding p.S107T) and c.382A→T (encoding p.M128R) in 2 patients with sporadic multiple-system atrophy; COQ2 c.1178T→C (p.V393A) was not associated with multiple-system atrophy (MAF, 2.7% of cases vs. 2.6% of controls). It is a challenge to reconcile recessive linkage of homozygous COQ2 mutations in familial multiple-system atrophy with a heterozygous, presumably dominant-negative association in sporadic multiple-system atrophy. Respectfully, we suggest that Tsuji and colleagues reconsider whether variations in COQ2 represent a risk factor for multiple-system atrophy. Genomic multiplications of the SNCA 6.4-Mb locus telomeric to COQ2 have previously been implicated in parkinsonism and multiple-system atrophy3; copy number analysis of linked loci, or genomewide analysis, should be considered.

The objective of this work was to investigate the influence of the composition of biomass on the release of different trace elements during gasification. To cover a broad range of fuels three types of woody biomass and four types of biomass residues were used. The present experiments were performed at different temperatures (1200¬1400 °C), under gasification like conditions. The experiments were carried out in an atmospheric flow channel reactor furnace. For the determination of the composition of the product gas, the flow channel reactor was coupled to a molecular beam mass spectrometer (MBMS). The hot gases were directly analysed in real¬time by MBMS. The focus was on the alkali metals (K and Na) and on the non metals (S, Cl and P) that are expected to affect the solid and gas phase chemistry and volatility of the other elements. The main gaseous species were: 36HCl+, 58NaCl+, 74KCl+, 64+3460+SO2 , H2S+, COS+, and 63PO2 . After quantification, the data set was correlated with the elemental composition of the biomass and the release mechanisms are discussed., Proceedings of the 20th European Biomass Conference and Exhibition, 18-22 June 2012, Milan, Italy, pp. 869-874

The search for novel chemotherapeutic agents and approaches to cancer treatment is an active research field stimulated by the discovery of new biological targets and by the possibility of obtaining new drugs without serious and undesirable side effects. Several anticancer agents have been developed so far based on different mechanism of action; despite this, intercalator agents still remain an interesting class of molecules to focus on. In particular, in the literature there are several examples of Naphthalimmide and 1,4,5,8-Naphtalentetracaboxylic diimide derivatives as intercalating and anticancer agents. It is well-known that, at physiological pH, protonated polyamines interact strongly with the phosphate residues of DNA. Therefore, the inclusion of these basic functionalities, on an intercalating moiety, may improve the interaction with DNA structure. Recently, we reported on the design and synthesis of substituted Naphtalen(di)immides as anticancer agents (1). Among the several developed compounds, 1 and 2 were the most interesting derivatives showing the ability to bind DNA, trigger caspase activation, cause accumulation of p53 protein, down-regulate the survival kinase AKT, cause a decrease of ERK1/2 and, inhibit ERK’s phosphorylation. The aim of the present work is to further investigate the promising biological profile of 1 and 2, and the role of the 2-methoxy substituents on the benzyl moieties, For this purpose several analogues, with different substituents on the two aromatic rings, were synthesized evaluated for their antiproliferative activity. This research was supported by grants from MUR, the University of Bologna, and Polo Scientifico-Didattico di Rimini. We thank the National Cancer Institute for the anticancer assays. (1) Tumiatti, V., et al. J. Med. Chem. 2009, 52, 7873-7.