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Background: Strategies for the involvement of primary care in the management of patients with presumed or diagnosed dementia are heterogeneous across Europe. We wanted to explore attitudes of primary care physicians (PCPs) when managing dementia: (i) the most popular cognitive tests, (ii) who had the right to initiate or continue cholinesterase inhibitor or memantine treatment, and (iii) the relationship between the permissiveness of these rules/guidelines and PCP's approach in the dementia investigations and assessment., Methods: Key informant survey., Setting: Primary care practices across 25 European countries., Subjects: Four hundred forty-five PCPs responded to a self-administered questionnaire. Two-step cluster analysis was performed using characteristics of the informants and the responses to the survey., Main Outcome Measures: Two by two contingency tables with odds ratios and 95% confidence intervals were used to assess the association between categorical variables. A multinomial logistic regression model was used to assess the association of multiple variables (age class, gender, and perceived prescription rules) with the PCPs' attitude of "trying to establish a diagnosis of dementia on their own.", Results: Discrepancies between rules/guidelines and attitudes to dementia management was found in many countries. There was a strong association between the authorization to prescribe dementia drugs and pursuing dementia diagnostic work-up (odds ratio, 3.45; 95% CI 2.28-5.23)., Conclusions: Differing regulations about who does what in dementia management seemed to affect PCP's engagement in dementia investigations and assessment. PCPs who were allowed to prescribe dementia drugs also claimed higher engagement in dementia work-up than PCPs who were not allowed to prescribe.

Introduction: Chronic peripheral neuropathic pain (CPNP) is a condition due to peripheral nervous system diseases or injury, but its prevalence is unknown in Italian primary care., Aim: The aim of this study is to assess the prevalence of CPNP in a rural primary care area in Northern Italy., Materials and Methods: A multicenter audit study was carried out in a rural area in Northern Italy with 113 participating general practitioners (GPs) seeing 58,480 patients >18 years during 3 months. Patients who for any reason attended GPs' surgeries and had symptoms suggestive of neuropathic pain (NP) were given the NP diagnostic questionnaire "Douleur Neuropathique en 4 Questions" (DN4) and recorded their pain level on a visual analog scale (VAS)., Results: Chronic NP was established by a DN4 score of ≥4 and a VAS pain score of ≥40 mm for >6 months together with a clinical diagnosis in 448 (254 women and 194 men) out of 58,480 patients giving a prevalence of 0.77%. 179 patients (0.31%) had diabetes neuropathy, 142 (0.24%) had postherpetic pain, 41 (0.07%) had trigeminal neuralgia, 27 (0.05%) had NP postinjury, 27 (0.05%) had NP caused by nerve entrapments, 11 (0.02%) had NP triggered by systemic diseases, and 21 (0.04%) had NP of unknown etiology., Conclusions: The prevalence of CPNP in this population of primary care attenders in a rural area in Northern Italy was 0.77%. Diabetes neuropathy (0.31%) and postherpetic pain (0.24%) were the two most common subgroups of NP, followed by trigeminal neuralgia (0.07%)., Competing Interests: There are no conflicts of interest.

Introduction: The implementation of lifelong antiretroviral treatment (ART) for all pregnant women (Option B+) in Malawi has resulted in a significant increase in the number of HIV-positive pregnant women initiating treatment. However, research has highlighted the challenge of retaining newly initiated women in care. This study explores barriers and facilitators that affect a woman's decision to initiate and to adhere to Option B+., Methods: A total of 39 in-depth interviews and 16 focus group discussions were conducted. Eligible women were ≥18 years old, living with HIV and either pregnant and receiving antenatal care from a study site or had delivered a child within the last 18 months, breastfed their child and received services at one of the study sites. Eligible women were identified by healthcare workers (HCWs) in the antenatal clinic and ART unit. Focus groups were also conducted with HCWs employed in these departments. Qualitative data were analyzed using Maxqda version 10 (VERBI Software, Berlin, Germany)., Results: The general perception towards the drug regimen used in Option B+ was positive; women reported fewer side effects and acknowledged the positive benefits of ART. Women felt hopeful about prolonging their life and having an HIV-uninfected baby, yet grappled with the fact that ART is a lifelong commitment. Women and HCWs discussed challenges with the counselling services for prevention of mother-to-child HIV transmission under the new Option B+ guidelines, and many women struggled with initiating ART on the same day as learning their HIV status. Women wanted to discuss their circumstances with their husbands first, receive a CD4 count and obtain an HIV test at another facility to confirm their HIV status. HCWs expressed concern that women might just agree to take the drugs to please them. HCWs also discussed concerns around loss to follow-up and drug resistance., Conclusions: Although Option B+ has significantly increased the number of women initiating ART, there are still challenges that need to be addressed to strengthen initiation, adherence and retention in care. Strategies to strengthen the counselling services upon diagnosis need to be developed to improve same-day initiation of ART and long-term adherence.

Internal parasites are a significant determinant of the productivity of ruminant species in the tropics. Provision of anthelmintics has become a predominant part of animal health interventions in emergency drought responses, aiming to maintain the food conversion efficiency of livestock when pasture is scarce. This study aimed to assess the owner-perceived impact of anthelmintic provision on the health and productivity of small ruminants in the drought-prone counties of Isiolo and Marsabit, northern Kenya. Participatory approaches were used to retrospectively measure differences in key indicators of livestock output before and after anthelmintic administration. Results showed that there was no perceived impact of anthelmintic administration during droughts on small ruminant health and productivity, but some benefit of anthelmintic administration during rainy season was perceived. The study also provided some evidence of potential differences in the epidemiology of internal parasites between the counties. These findings may be utilised to inform future livestock intervention programmes in drought-prone areas.

Introduction: Streptococcus agalactiae (Group B streptococcus [GBS]) is the most common cause of sepsis and meningitis in infants <3 months of age. Intrapartum antibiotic prophylaxis (IAP) is effective in preventing the transmission of GBS to newborns. The Centers for Disease Control and Prevention (CDC) guidelines suggest vaginal and rectal cultures to assess GBS colonization between 35 and 37 weeks' gestation., Methods: Between July and December 2013, we identified 535 women admitted to the Obstetric and Gynecology Unit of Cardarelli Hospital (Campobasso, Italy) for delivery. We evaluated the indications for IAP, complete execution of IAP, and neonatal outcomes., Results: Our sample included 468 women and 475 live births. Correct screening for GBS was executed in 241 cases (51.5%), the number of women colonized was 96 (30.2%), and 136 women had indications to receive IAP, but only 68 (50%) received adequate treatment., Conclusions: GBS colonization status should be determined by collecting both vaginal and rectal specimens at 35-37 weeks' gestation. Inadequate screening for GBS and incorrect IAP led to an increased incidence of early-onset disease in newborns. Local public health agencies should promote surveillance and educational programs to prevent neonatal GBS infections.

Autosomal recessive inherited ataxias are a growing group of genetic disorders. We report two Italian siblings presenting in their mid-50s with difficulty in walking, dysarthria and progressive cognitive decline. Visual loss, ascribed to glaucoma, manifested a few years before the other symptoms. Brain MRI showed severe cerebellar atrophy, prevalent in the vermis, with marked cortical atrophy of both hemispheres. Exome sequencing identified a novel homozygous mutation (c.935G > A;p.Ser312Asn) in the ceroid neuronal lipofuscinosis type 5 gene (CLN5). Bioinformatics predictions and in vitro studies showed that the mutation was deleterious and likely affects ER-lysosome protein trafficking. Our findings support CLN5 hypomorphic mutations cause autosomal recessive cerebellar ataxia, confirming other reports showing CLN mutations are associated with adult-onset neurodegenerative disorders. We suggest CLN genes should be considered in the molecular analyses of patients presenting with adult-onset autosomal recessive cerebellar ataxia.

Research in family medicine is a well-established entity nationally and internationally, covering all aspects of primary care including remote and isolated practices. However, due to limited capacity and resources in rural family medicine, its potential is not fully exploited yet. An idea to foster European rural primary care research by establishing a practice-based research network has been recently put forward by several members of the European Rural and Isolated Practitioners Association (EURIPA) and the European General Practice Research Network (EGPRN). Two workshops on why, and how to design a practice-based research network among rural family practices in Europe were conducted at two international meetings. This paper revisits the definition of practice-based research in family medicine, reflects on the current situation in Europe regarding the research in rural family practice, and discusses a rationale for practice-based research in rural family medicine. A SWOT analysis was used as the main tool to analyse the current situation in Europe regarding the research in rural family practice at both meetings. The key messages gained from these meetings may be employed by the Wonca Working Party on research, the International Federation of Primary Care Research Network and the EGPRN that seek to introduce a practice-based research approach. The cooperation and collaboration between EURIPA and EGPRN creates a fertile ground to discuss further the prospect of a European practice-based rural family medicine research network, and to draw on the joint experience.

Background: A Quick Test of Cognitive Speed (AQT) is a brief test that can identify cognitive impairment. AQT has been validated in Arabic, English, Greek, Japanese, Norwegian, Spanish, and Swedish. The aim of this study was to develop Italian criterion-referenced norms for AQT., Methods: AQT consists of three test plates where the patient shall rapidly name (1) the color of 40 blue, red, yellow, or black squares (AQT color), (2) the form of 40 black figures (circles, squares, triangles, or rectangles; AQT form), (3) the color and form of 40 figures (consisting of previous colors and forms; AQT color-form). The AQT test was administered to 121 Italian cognitively healthy primary care patients (age range: 45-90 years). Their mean Mini-Mental State Examination (MMSE) score was 28.8 ± 0.9 points (range 26-30 points). AQT naming times in seconds were used for developing preliminary criterion cut-off times for different age groups., Results: Age was found to have a significant moderate positive correlation with AQT naming times color (r = 0.65, p < 0.001), form (r = 0.53, p < 0.001), color-form (r = 0.63, p < 0.001) and a moderate negative correlation with MMSE score (r = -0.44, p < 0.001) and AQT naming times differed significantly between younger (45-55 years old), older (56-70 years old), and the oldest (71-90 years old) participants. Years of education correlated positively but weakly with MMSE score (r = 0.27, p = 0.003) and negatively but weakly with AQT color (r = -0.16, p = ns), form (r = -0.24, p = 0.007), and color-form (r = -0.19, p = 0.005). We established preliminary cut-off times for the AQT test based on +1 and +2 standard deviations according to the approach in other languages and settings., Conclusions: This is the first Italian normative AQT study. Future studies of AQT - a test useful for dementia screening in primary care - will eventually refine cut-off times for normality balancing sensitivity and specificity in cognitive diagnostics.

Malignant mesothelioma is a deadly tumor whose diagnosis and treatment remain very challenging. There is an urgent need to advance our understanding of mesothelioma biology and to identify new molecular markers for improving management of patients. CD157 is a membrane glycoprotein linked to ovarian cancer progression and mesenchymal differentiation. The common embryonic origin of ovarian epithelial cells and mesothelial cells and the evident similarities between ovarian and mesothelial cancer prompted us to investigate the biological role and clinical significance of CD157 in malignant pleural mesothelioma (MPM). CD157 mRNA and protein were detected in four of nine MPM cell lines of diverse histotype and in 85.2% of MPM surgical tissue samples (32/37 epithelioid; 37/44 biphasic). CD157 expression correlated with clinical aggressiveness in biphasic MPM. Indeed, high CD157 was a negative prognostic factor and an independent predictor of poor survival for patients with biphasic MPM by multivariate survival analysis (HR = 2.433, 95% CI 1.120-5.284; p = 0.025). In mesothelioma cell lines, CD157 gain (in CD157-negative cells) or knockdown (in CD157-positive cells) affected cell growth, migration, invasion and tumorigenicity, most notably in biphasic MPM cell lines. In these cells, CD157 expression was associated with increased activation of the mTOR signaling pathway, resulting in decreased platinum sensitivity. Moreover, a trend towards reduced survival was observed in patients with biphasic MPM receiving postoperative platinum-based chemotherapy. These findings indicate that CD157 is implicated in multiple aspects of MPM progression and suggest that CD157 expression could be used to stratify patients into different prognostic groups or to select patients that might benefit from particular chemotherapeutic approach.

Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal-dominant neurodegenerative disorders involving the cerebellum and 23 different genes. We mapped SCA38 to a 56 Mb region on chromosome 6p in a SCA-affected Italian family by whole-genome linkage analysis. Targeted resequencing identified a single missense mutation (c.689G>T [p.Gly230Val]) in ELOVL5. Mutation screening of 456 independent SCA-affected individuals identified the same mutation in two further unrelated Italian families. Haplotyping showed that at least two of the three families shared a common ancestor. One further missense variant (c.214C>G [p.Leu72Val]) was found in a French family. Both missense changes affect conserved amino acids, are predicted to be damaging by multiple bioinformatics tools, and were not identified in ethnically matched controls or within variant databases. ELOVL5 encodes an elongase involved in the synthesis of polyunsaturated fatty acids of the ω3 and ω6 series. Arachidonic acid and docosahexaenoic acid, two final products of the enzyme, were reduced in the serum of affected individuals. Immunohistochemistry on control mice and human brain demonstrated high levels in Purkinje cells. In transfection experiments, subcellular localization of altered ELOVL5 showed a perinuclear distribution with a signal increase in the Golgi compartment, whereas the wild-type showed a widespread signal in the endoplasmic reticulum. SCA38 and SCA34 are examples of SCAs due to mutations in elongase-encoding genes, emphasizing the importance of fatty-acid metabolism in neurological diseases., (Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

The major ADP-ribosylating enzyme families are the focus of this special issue of Frontiers in Bioscience . However, there is room for another family of enzymes with the capacity to utilize nicotinamide adenine dinucleotide (NAD): the ADP-ribosyl cyclases (ARCs). These unique enzymes catalyse the cyclization of NAD to cyclic ADP ribose (cADPR), a widely distributed second messenger. However, the ARCs are versatile enzymes that can manipulate NAD, NAD phosphate (NADP) and other substrates to generate various bioactive molecules including nicotinic acid adenine dinucleotide diphosphate (NAADP) and ADP ribose (ADPR). This review will focus on the group of well-characterized invertebrate and vertebrate ARCs whose common gene structure allows us to trace their origin to the ancestor of bilaterian animals. Behind a facade of gene and protein homology lies a family with a disparate functional repertoire dictated by the animal model and the physical trait under investigation. Here we present a phylogenetic view of the ARCs to better understand the evolution of function in this family.

CD157/BST-1 behaves both as an ectoenzyme and signaling receptor and is an important regulator of leukocyte trafficking and ovarian cancer progression. However, the molecular interactions underpinning the role of CD157 in these processes remain obscure. The biological functions of CD157 and its partnership with members of the integrin family prompted us to assume the existence of a direct interaction between CD157 and an unknown component of the extracellular matrix. Using solid-phase binding assays and surface plasmon resonance analysis, we demonstrated that CD157 binds fibronectin with high affinity within its heparin-binding domains 1 and 2. Furthermore, we found that CD157 binds to other extracellular matrix proteins containing heparin-binding domains. Finally, we proved that the CD157-fibronectin interaction occurs with living cells, where it elicits CD157-mediated cell responses. Indeed, knockdown of CD157 in Met-5A mesothelial cells changed their morphology and cytoskeleton organization and attenuated the activation of intracellular signaling pathways triggered by fibronectin. This led to impaired cell spreading and adhesion to selected extracellular matrix proteins. Collectively, these findings indicate a central role of CD157 in cell-extracellular matrix interactions and make CD157 an attractive therapeutic target in inflammation and cancer., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

We aimed at investigating in vitro the cytotoxic activity (determined using WST-1, apoptosis and cell cycle assays) of gemcitabine, alone or in combination with mitotane, in mitotane-sensitive H295R and mitotane-insensitive SW-13 cells. Results of these experiments were compared with drug-induced modulation of RRM1 gene, the specific target of gemcitabine. In H295R cells, mitotane and gemcitabine combinations showed antagonistic effects and interfered with the gemcitabine-mediated inhibition of the S phase of the cell cycle. By contrast, in SW-13 cells, except when mitotane was sequentially administered prior to gemcitabine, the combination of the two drugs was synergistic. Such opposite effects were associated with opposite expression profiles of the target gene, with significant up-modulation in H295R but not in SW-13 under gemcitabine and mitotane combination treatment., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

CD157 is a member of the ADP-ribosyl cyclase gene family that is involved in the metabolism of NAD. CD157 behaves both as an ectoenzyme and as a receptor. Though CD157 is anchored to the membrane by a glycosylphosphatidylinositol moiety, which makes it unsuitable to transduce signals on its own, it exploits its localization in selected membrane microdomains and its proclivity to interact with integrins to accomplish receptor functions. Initially characterized as a stromal and myeloid antigen involved in the control of leukocyte adhesion, migration and diapedesis, CD157 was subsequently found to have a far wider distribution. In particular, CD157 was found to be expressed by epithelial ovarian cancer cells where it is involved in interactions among tumor cells, extracellular matrix proteins and mesothelium. The overall picture inferred from experimental and clinical observations is that CD157 is a critical player both in leukocyte trafficking and in ovarian cancer invasion and metastasis formation. In this review, we will discuss the biological mechanisms underpinning the role of CD157 in the control of leukocyte migration and ovarian cancer dissemination.

Objective: To document family medicine research in the 25 EGPRN member countries in 2010., Design: Semi-structured survey with open-ended questions., Setting: Academic family medicine in 23 European countries, Israel, and Turkey., Subjects: 25 EGPRN national representatives., Main Outcome Measures: Demographics of the general population and family medicine. Assessments, opinions, and suggestions., Results: EGPRN has represented family medicine for almost half a billion people and > 300,000 general practitioners (GPs). Turkey had the largest number of family medicine departments and highest density of GPs, 2.1/1000 people, Belgium had 1.7, Austria 1.6, and France 1.5. Lowest GP density was reported from Israel 0.17, Greece 0.18, and Slovenia 0.4 GPs per 1000 people. Family medicine research networks were reported by 22 of 25 and undergraduate family medicine research education in 20 of the 25 member countries, and in 10 countries students were required to do research projects. Postgraduate family medicine research was reported by 18 of the member countries. Open-ended responses showed that EGPRN meetings promoted stimulating and interesting research questions such as comparative studies of chronic pain management, sleep disorders, elderly care, healthy lifestyle promotion, mental health, clinical competence, and appropriateness of specialist referrals. Many respondents reported a lack of interest in family medicine research related to poor incentives and low family medicine status in general and among medical students in particular. It was suggested that EGPRN exert political lobbying for family medicine research., Conclusion: Since 1974, EGPRN organizes biannual conferences that unite and promote primary care practice, clinical research and academic family medicine in 25 member countries.

Background: SCA28 is an autosomal dominant ataxia associated with AFG3L2 gene mutations. We performed a whole genome expression profiling using lymphoblastoid cell lines (LCLs) from four SCA28 patients and six unrelated healthy controls matched for sex and age., Methods: Gene expression was evaluated with the Affymetrix GeneChip Human Genome U133A 2.0 Arrays and data were validated by real-time PCR., Results: We found 66 genes whose expression was statistically different in SCA28 LCLs, 35 of which were up-regulated and 31 down-regulated. The differentially expressed genes were clustered in five functional categories: (1) regulation of cell proliferation; (2) regulation of programmed cell death; (3) response to oxidative stress; (4) cell adhesion, and (5) chemical homeostasis. To validate these data, we performed functional experiments that proved an impaired SCA28 LCLs growth compared to controls (p < 0.005), an increased number of cells in the G0/G1 phase (p < 0.001), and an increased mortality because of apoptosis (p < 0.05). We also showed that respiratory chain activity and reactive oxygen species levels was not altered, although lipid peroxidation in SCA28 LCLs was increased in basal conditions (p < 0.05). We did not detect mitochondrial DNA large deletions. An increase of TFAM, a crucial protein for mtDNA maintenance, and of DRP1, a key regulator of mitochondrial dynamic mechanism, suggested an alteration of fission/fusion pathways., Conclusions: Whole genome expression profiling, performed on SCA28 LCLs, allowed us to identify five altered functional categories that characterize the SCA28 LCLs phenotype, the first reported in human cells to our knowledge.

Epithelial ovarian carcinoma (EOC) is an aggressive tumor often diagnosed at an advanced stage, when there is little or no prospect of cure. Despite advances in surgical and chemotherapeutic strategies, only marginal improvements in patient outcome have been obtained. Hence, unraveling the biological mechanisms underpinning EOC progression is critical for improving patients' survival. Recently, we reported that CD157 (an ectoenzyme regulating leukocyte diapedesis) is expressed in EOC and that high expression of the molecule is negatively correlated with the disease outcome in patients. Here, we demonstrate that forced overexpression of CD157 in OVCAR-3, TOV-21G, A2780 and OV-90 ovarian cancer cell lines promotes morphological and phenotypic changes characterized by disruption of intercellular junctions, downregulation of epithelial markers and upregulation of mesenchymal ones. These changes in cell shape and phenotype bring to reduced sensitivity to anoikis, increased anchorage-independent growth, cell motility and mesothelial invasion. Conversely, knockdown of CD157 in OV-90 and OC314 cells reverts the mesenchymal phenotype and reduces the cells' migratory potential. Transcriptome profiling analysis highlighted 378 significantly differentially expressed genes, representing the signature of CD157-overexpressing OVCAR-3 and OV-90 cells. The modulation of selected genes translates into alteration of protein expression that give cells a highly malignant phenotype. The overall picture deduced from the analysis of the modulated transcripts is that high expression of CD157 strengthens a number of biological processes favoring tumor progression (including development and cell motility), and weakens several biological processes hindering tumor progression (such as apoptosis, cell death and response to stress). Together, these findings implicate CD157 in the progression of EOC to metastatic disease and suggest that CD157 may represent a valuable therapeutic target.

CD157, a member of the CD38 gene family, is an NAD-metabolizing ectoenzyme and a signaling molecule whose role in polarization, migration, and diapedesis of human granulocytes has been documented; however, the molecular events underpinning this role remain to be elucidated. This study focused on the role exerted by CD157 in monocyte migration across the endothelial lining and adhesion to extracellular matrix proteins. The results demonstrated that anti-CD157 antibodies block monocyte transmigration and adhesion to fibronectin and fibrinogen but that CD157 cross-linking is sufficient to overcome the block, suggesting an active signaling role for the molecule. Consistent with this is the observation that CD157 is prevalently located within the detergent-resistant membrane microdomains to which, upon clustering, it promotes the recruitment of β(1) and β(2) integrin, which, in turn, leads to the formation of a multimolecular complex favoring signal transduction. This functional cross-talk with integrins allows CD157 to act as a receptor despite its intrinsic structural inability to do so on its own. Intracellular signals mediated by CD157 rely on the integrin/Src/FAK (focal adhesion kinase) pathway, resulting in increased activity of the MAPK/ERK1/2 and the PI3K/Akt downstream signaling pathways, which are crucial in the control of monocyte transendothelial migration. Collectively, these findings indicate that CD157 acts as a molecular organizer of signaling-competent membrane microdomains and that it forms part of a larger molecular machine ruled by integrins. The CD157-integrin partnership provides optimal adhesion and transmigration of human monocytes.

Background: CD157, an ADP-ribosyl cyclase-related cell surface molecule, regulates leukocyte diapedesis during inflammation. Because CD157 is expressed in mesothelial cells and diapedesis resembles tumor cell migration, we investigated the role of CD157 in ovarian carcinoma., Methods: We assayed surgically obtained ovarian cancer and mesothelial cells and both native and engineered ovarian cancer cell lines for CD157 expression using flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR), and for adhesion to extracellular matrices, migration, and invasion using cell-based assays. We investigated invasion of human peritoneal mesothelial cells by serous ovarian cancer cells with a three-dimensional coculture model. Experiments were performed with or without CD157-blocking antibodies. CD157 expression in tissue sections from ovarian cancer patients (n = 88) was examined by immunohistochemistry, quantified by histological score (H score), and categorized as at or above or below the median value of 60, and compared with clinical parameters. Statistical tests were two-sided., Results: CD157 was expressed by ovarian cancer cells and mesothelium, and it potentiated the adhesion, migration, and invasion of serous ovarian cancer cells through different extracellular matrices. CD157-transfected ovarian cancer cells migrated twice as much as CD157-negative control cells (P = .001). Blockage of CD157 inhibited mesothelial invasion by serous ovarian cancer cells in a three-dimensional model. CD157 was expressed in 82 (93%) of the 88 epithelial ovarian cancer tissue specimens. In serous ovarian cancer, patients with CD157 H scores of 60 or greater had statistically significantly shorter disease-free survival and overall survival than patients with lower CD157 H scores (CD157 H score > or =60 vs <60: median disease-free survival = 18 months, 95% confidence interval [CI] = 5.92 to 30.07 vs unreached, P = .005; CD157 H score > or =60 vs <60: median overall survival = 45 months, 95% CI = 21.21 to 68.79 vs unreached, P = .024). Multivariable Cox regression showed that CD157 is an independent prognostic factor for recurrence (hazard ratio of disease recurrence = 3.01, 95% CI = 1.35 to 6.70, P = .007) and survival (hazard ratio of survival = 3.44, 95% CI = 1.27 to 9.31, P = .015)., Conclusions: CD157 plays a pivotal role in the control of ovarian cancer cell migration and peritoneal invasion, and it may be clinically useful as a prognostic tool and therapeutic target.

CD157 is a glycosylphosphatidylinositol-anchored molecule encoded by a member of the CD38/ADP-ribosyl cyclase gene family, involved in the metabolism of NAD. Expressed mainly by cells of the myeloid lineage and by vascular endothelial cells, CD157 has a dual nature behaving both as an ectoenzyme and as a receptor. Although it lacks a cytoplasmic domain, and cannot transduce signals on its own, the molecule compensates for this structural limit by interacting with conventional receptors. Recent experimental evidence suggests that CD157 orchestrates critical functions of human neutrophils. Indeed, CD157-mediated signals promote cell polarization, regulate chemotaxis induced through the high affinity fMLP receptor and control transendothelial migration.

Background: Human monoclonal antibodies (mAbs) generated as a result of the immune response are likely to be the most effective therapeutic antibodies, particularly in the case of infectious diseases against which the immune response is protective.Human cytomegalovirus (HCMV) is an ubiquitous opportunistic virus that is the most serious pathogenic agent in transplant patients. The available therapeutic armamentarium (e.g. HCMV hyperimmune globulins or antivirals) is associated with severe side effects and the emergence of drug-resistant strains; therefore, neutralizing human mAb may be a decisive alternative in the prevention of primary and re-activated HCMV infections in these patients., Results: The purpose of this study was to generate neutralizing mAb against HCMV from the immunological repertoire of immune donors. To this aim, we designed an efficient technology relying on two discrete and sequential steps: first, human B-lymphocytes are stimulated with TLR9-agonists and IL-2; second, after both additives are removed, the cells are infected with EBV. Using this strategy we obtained 29 clones secreting IgG neutralizing the HCMV infectivity; four among these were further characterized. All of the mAbs neutralize the infection in different combinations of HCMV strains and target cells, with a potency approximately 20 fold higher than that of the HCMV hyperimmune globulins, currently used in transplant recipients. Recombinant human monoclonal IgG1 suitable as a prophylactic or therapeutic tool in clinical applications has been generated., Conclusion: The technology described has proven to be more reproducible, efficient and rapid than previously reported techniques, and can be adopted at low overall costs by any cell biology laboratory for the development of fully human mAbs for immunotherapeutic uses.

Our study is aimed to evaluate the change of QT/QS2 ratio in normal subjects during both isometric and dynamic exercise before and after propranolol administration. We studied 10 young volunteers healthy subjects who performed an isometric exercise by squeezing a grip dynamometer at 70% of their maximal voluntary contraction as long as possible. They also performed a dynamic exercise undergoing a submaximal bicycle stress test. Both tests were performed before and after administration of propranolol (0.15 mg/Kg e.v.) QT and QS2 intervals were measured at rest, during exercise and in the recovery period. Heart rate and blood pressure were also determined. Isometric exercise induces a significant shortening of both intervals although minor for QT so that the ratio significantly increases in comparison to baseline (p less than .001). At rest propranolol induces a significant decrease of heart rate and only a slight lengthening of QT and QS2 so that the ratio is unchanged. During exercise propranolol does not influence the increase of heart rate and blood pressure and the shortening of QT interval but prevent exercise-induced QS2 shortening so that the ratio after beta-blockade is significantly reduced at the peak of exercise (p less than .005). During dynamic exercise QT and QS2 behaviour is similar to that of isometric exercise; in fact both intervals are shortened and QS2 decrease is major than QT so that the ratio increases (p less than .001). These results confirm that QT/QS2 ratio can monitor the effects of adrenergic stimulation on the heart during physiological manoeuvres enhancing sympathetic discharge like occurs during both isometric and dynamic exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of severity of coronary artery disease (CAD) on the duration of corrected electrical systole (QTc) and the prognostic value to predict sudden death of this index were retrospectively evaluated in 123 non-consecutive patients with history of stable angina who underwent cardiac catheterization. Fifteen patients had no angiographic evidence of CAD (O-V group). The 108 patients with a greater than or equal to 70% luminal diameter narrowing of a major coronary artery were further subdivided: 23 patients had 1-vessel (1-V group), 40 patients had 2-vessel (2-V group) and 45 had 3-vessel (3-V group) coronary artery disease; 26 patients showed normal left ventricular (LV) wall motion (A group), 57 patients showed asynergic contraction of 1 or 2 LV areas (B group) and 25 patients showed 3 or more areas of asynergy and/or aneurysm. Sixty-one patients had a previous myocardial infarction (MI). QT interval, calculated in the lead where it was longer, on 12-lead resting electrocardiograms recorded at a paper speed of 25 mm/sec, was corrected by the formula: QTc = QT/square root R-R. The follow-up was performed by telephone. At the time of angiography there was no significant difference in QTc duration between the different groups according to the severity of CAD (O-V, 1-V, 2-V and 3-V groups). Patients showing three or more areas of abnormal segmental wall motion and/or aneurysm (C group) had a significantly longer QTc (p less than 0.05) than patients with normal LV wall motion (A group).(ABSTRACT TRUNCATED AT 250 WORDS)