Search

Serial muscle biopsies within clinical trials for Duchenne muscular dystrophy (DMD) are critical to document therapeutic responses. Less invasive means of sampling muscle are needed. We analyzed a retrospective consecutive case-series cohort of vacuum-assisted core needle muscle biopsy procedures performed on healthy and dystrophic individuals at a single institution assessing for safety and reliability of obtaining sufficient high-quality biopsy tissue for histologic assessment in adult and pediatric subjects. Of 471 muscle cores from 128 biopsy procedures, 377-550 mg of total muscle tissue was obtained per procedure with mean core weight of 129 mg (SD, 25.1 mg). All biopsies were adequate for histological assessment. There were no significant adverse events. This core needle biopsy approach, when combined with improved sample processing, provides a safe means to consistently obtain muscle samples for diagnostic and clinical trial applications. [ABSTRACT FROM AUTHOR]

Objectives To estimate the influence of educational level and oral hygiene behaviours on the prevalence and severity of dental caries and periodontal disease in an adult Italian population attending the Oral Hygiene department of a public Dental Clinic. Methods Dental caries was diagnosed according to the World Health Organization criteria. The DMFT index (decayed, missing, filled tooth) was used to record the dental caries' experience. The periodontal status was assessed using the community periodontal index of treatment needs ( CPITN). Questionnaires on educational level and oral hygiene behaviours were also collected. Results A total of 350 patients were enrolled. The mean DMFT value reported was 4.37 ± 3.06, and higher values were observed for male patients ( P < 0.05). Increased CPITN scores and DMFT values were significantly correlated with lower level of education ( P < 0.05). Subjects of high educational status showed significantly better oral hygiene habits ( P < 0.05). Conclusions The oral health status, in terms of periodontal disease and dental caries, appears correlated with patients' educational level. [ABSTRACT FROM AUTHOR]

Objectives. Fibroblast growth factor-23 (FGF-23) and vitamin D are hormones involved in phosphate homoeostasis. They also directly influence cardiomyocyte hypertrophy. We examined whether the relationships between levels of vitamin D or FGF- 23, cardiac phenotype and outcome were independent of established cardiac biomarkers in a large cohort of community-dwelling elderly subjects. Design and Setting. Plasma levels of FGF-23 and vitamin D were measured in 1851 men and women (65-84 years) resident in the Lazio region of Italy. Participants were referred to eight cardiology centres for clinical examination, electrocardiography, comprehensive Doppler echocardiography and blood sampling. All-cause mortality or hospitalizations were available after a median follow-up of 47 months with record linkage of administrative data. Results. Vitamin D deficiency (<20 ng mL-1) was found in 72.3% of subjects, but FGF-23 levels were normal [74 (58-97) RU per mL]. After adjustment for cardiovascular risk factors and morbidities, low concentrations of vitamin D and high levels of FGF-23 were associated with a higher left ventricular (LV) mass index. Levels of FGF-23 [hazard ratio (HR) (95% confidence interval (CI)) 1.71 (1.28-2.28), P < 0.0001] but not vitamin D [0.76 (0.57-1.01), P = 0.08] were independently associated with mortality after adjustment for clinical risk factors and two cardiac markers together (N-terminal pro-brain natriuretic peptide and high-sensitivity cardiac troponin T), but did not predict hospital admission. People with above median values of FGF-23 and below median values of vitamin D had greater LV hypertrophy and higher mortality. Conclusions. In community-dwelling elderly individuals with highly prevalent vitamin D deficiency, FGF-23 levels were associated with LV hypertrophy and predicted mortality independently of two robust cardiac biomarkers. A causal relationship was not demonstrated, but the hormones involved in mineral metabolism emerged as nontraditional risk factors and may affect cardiovascular risk. [ABSTRACT FROM AUTHOR]

The spectral shape of the synchrotron X-ray emission from SN 1006 reveals the fundamental role played by radiative losses in shaping the high-energy tail of the electron spectrum. We analyze data from the XMM- Newton SN 1006 Large Program and confirm that in both nonthermal limbs the loss-limited model correctly describes the observed spectra. We study the physical origin of the observed variations of the synchrotron cutoff energy across the shell. We investigate the role played by the shock velocity and by the electron gyrofactor. We found that the cutoff energy of the synchrotron X-ray emission reaches its maximum value in regions where the shock has experienced its highest average speed. This result is consistent with the loss-limited framework. We also find that the electron acceleration in both nonthermal limbs of SN 1006 proceeds close to the Bohm diffusion limit, the gyrofactor being in the range η ∼ 1.5-4. We finally investigate possible explanations for the low values of cutoff energy measured in thermal limbs. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Objective To investigate the association between circulating cardiac biomarkers and minor abnormalities in cardiac phenotype [left ventricular ( LV) mass and midwall fractional shortening ( MFS)] in elderly individuals in a general population sample. Design and setting We examined the relationship between plasma concentrations of high-sensitivity cardiac troponin T (hs- cTnT) or N-terminal probrain natriuretic peptide ( NT-pro BNP) and elevated LV mass ( LV mass/body surface area >95 g m−2 for women and 115 g m−2 for men), reduced MFS (<15%) or isolated LV diastolic dysfunction in 1973 elderly subjects (mean age 73 ± 5 years, range 65-84) resident in the Lazio region of Italy and enrolled in the PREDICTOR study. Results Overall, 24.8% of subjects had elevated LV mass, and 30.4% had reduced MFS. Median [quartile 1-3] plasma concentrations of hs- cTnT and NT-pro BNP were higher in individuals with elevated than those with normal LV mass: 6.6 [3.5-11.6] and 147 [64-296] ng L−1 vs. 4.6 [3.0-8.1] and 79 [41-151] ng L−1 respectively ( P < 0.001). There was a graded increase in median hs- cTnT concentrations across clinical categories of LV hypertrophy: 4.6 [3.0-8.1], 5.8 [3.1-10.2], 7.6 [3.8-13.7] and 8.4 [3.8-17.6] ng L−1 for subjects with normal LV mass and mild, moderate or severe LV hypertrophy respectively ( P < 0.0001); hs- cTnT also increased with increasing quartiles of MFS or grades of isolated LV diastolic dysfunction. Conclusions Within an extremely low range of concentrations, increased hs- cTnT amongst community-dwelling elderly subjects is associated with subtle alterations in cardiac phenotype, suggesting that minor injury to cardiac myocytes and subsequent release of troponin reflect subclinical pathophysiological LV deterioration in this population. [ABSTRACT FROM AUTHOR]

This contribution summarizes the splinter session 'Non-thermal processes in coronae and beyond' held at the Cool Stars 17 workshop in Barcelona in 2012. It covers new developments in high energy non-thermal effects in the Earth's exosphere, solar and stellar flares, the diffuse emission in star forming regions and reviews the state and the challenges of the underlying atomic databases. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Objectives: Curative properties of medicinal plants such as Psidium guajava L. (Myrtaceae) have often been indicated by epidemiological studies on populations in which these fruits are consumed daily. However, complete characterization of the active principles responsible for this ability has never been performed. Here, we have characterized P. guajava's anti-cancer potential and identified the parts of the fruit involved in its anti-neoplastic action. Materials and methods: We studied morphology of our cells, cell cycle characteristics and apoptosis and performed immunostaining, differentiation and western blot analyses. Results: We report that the P. guajava extract exerted anti-cancer control on both haematological and solid neoplasias. P. guajava extract's anti-tumour properties were found to be tightly bound to induction of apoptosis and differentiation. Use of ex vivo myeloid leukaemia blasts corroborated that P. guajava was able to induce cell death but did not exhibit anti-cancer effects on all malignant cells investigated, indicating selective activity against certain types of tumour. Analyses of P. guajava pulp, peel and seeds identified the pulp as being the most relevant component for causing cell cycle arrest and apoptosis, whereas peel was responsible for causing cell differentiation. P. guajava itself and its pulp-derived extract were found to induce apoptosis accompanied by caspase activation and p16, p21, Fas ligand (FASL TNF super-family, member 6), Bcl-2-associated agonist of cell death (BAD) and tumour necrosis factor receptor super-family, member 10b (DR5), overexpression. Conclusions: Our findings showed that P. guajava L. extract was able to exert anti-cancer activity on cultures in vitro and ex vivo, supporting the hypothesis of its anti malignant pro-apoptotic modulation. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate a set of reference counts applied to multiparameter pre-counts in blood donors. Aim: Analyse the impact of pre-donation counts and specific reference intervals on donors' management. Background: Multiparameter blood counts allow an improved enrolment process of blood donors due to a prompt identification of abnormalities involving haemoglobin (Hb), white blood cells (WBC) and platelets (PLT). Methods/Materials: Multiple pre-donation capillary counts were applied in the enrolment process of 13 347 consecutive donors. The rate of specific alterations of permanent exclusion and donor readmittance to donations for temporary exclusion had been evaluated, applying a set of multiparameter reference intervals. Results: Alterations involved Hb in 72·55% of cases, mean corpuscular volume (MCV) in 20·99%, total WBC in 9·39%, lymphocytes in 7·55% and PLT in 6·07%. Among donors with initial alterations (543; 4·06%), 12·70% were readmitted to donations within 15 days, 14·36% had permanent exclusion, 36·83% underwent prompt supplementation treatment and 36·09% were lost at follow-up or refused treatments. Discussion: The systematic use of blood count reference intervals and pre-donation multiparameter blood counts allowed prompt identification of WBC, PLT and MCV alterations, readmittance within 15 days of 12·70% of initially excluded donors and contributed to prompt management of supplement deficiency. [ABSTRACT FROM AUTHOR]

Background and Objectives Blood donor enrolment process is frequently based on the sole capillary haemoglobin (Hb) evaluation while platelet donors by apheresis also requires platelet (Plt) count. The ‘sole Hb’ approach prevents a complete donor evaluation and does not allow Plt donor enrolment. To extend blood counts before donations, we evaluated the performances of a multiparametric counter using capillary blood. Materials and Methods The ABX Micros 60 (Micros 60) blood analyzer was employed on capillary blood and compared with venous counts by a reference counter (Coulter AcT 5diff) in a first series of 416 donors and in a second series of 136, after a 3-month period of routine use of this study counter. An average of 50 μl of capillary blood was collected whose 10 μl had been aspirated by Micros 60. Results High correlations were found between capillary counts using Micros 60 and venous counts using the reference counter. Mean Plt counts differed of 37 × 109/l less for capillary approach in the first series of comparisons, but decreased to 10 × 109/l less in the second series due to a greater expertise of operators in capillary sampling. All other parameters were accurate and never reached clinical relevance albeit they showed statistically significant differences. Conclusion Data on Micros 60 demonstrated that capillary predonation counts may represent a feasible and effective approach to realize an accurate enrolment process of blood and Plt donors. [ABSTRACT FROM AUTHOR]

Background Despite improvements in hepatitis B surface antigen (HBsAg) test sensitivity, post-transfusion hepatitis B virus (HBV) infection still occurs because HBsAg is undetectable during the early window phase (WP) of the infection, in the convalescence core window phase of the infection, or in serologically silent chronic hepatitis or in mutant forms of HBV. HBV-DNA screening using high sensitivity nucleic amplification technology (NAT) assays has recently been introduced to reduce the residual risk of transmission of HBV by transfusion of blood components. Materials Over 1 year 75 063 donations were individually screened for HBV-DNA by the Ultrio Procleix assay on the Tigris platform. The donations were collected in the Latium region, an area of the central Italy, and they accounted for the 40% of the total blood units collected in this area per year. The initial reactive samples were re-tested and confirmed by the discriminatory HBV assay. Additional HBV serological markers were also performed. Suspected WP infections were followed-up to monitor the development of the immune response. All HBV-DNA-positive donors were called back to check up their infectious status. Results The results of testing the 75 063 donations are: 33 donations HBsAg positive, 31 out of them HBV-DNA-positive and two HBV-DNA negative; 22 donations HBsAg-negative but HBV-DNA positive with low viral load. Six of the 22 were found to be consistently HBV-DNA reactive whereas the remaining 16 donations showed inconsistent results on multiple NAT retesting. One WP infection was confirmed by the follow-up of the donor for 3 months following the index blood donation. Conclusions In the donor population of the Latium region, NAT screening has revealed a higher than expected number of donors who were HBsAg non-reactive but HBV-DNA-positive with three donors showing HBV-DNA as the only marker of infection. The adoption of genome screening has increased the safety of the blood supply and has also contributed to the protection of donor health by identifying either WP or clinically silent infections. [ABSTRACT FROM AUTHOR]

In the current literature there is a great confusion between coping and defense mechanisms. As Cramer (1998) points out, a distinction between them is both possible and worthwhile in that they possess different cognitive features. Cramer proposes two basic criteria: the conscious/unconscious and the intentional/unintentional nature of the processes. We focus on a further criterion, the manipulation versus revision of one's mental attitudes, which so far has been neglected in the relevant literature. We suggest that responses to adversity implying manipulation are typical of defense mechanisms, while those implying the revision of one's mental attitudes characterize coping strategies. Finally, we address emotion-focused coping as the area where coping and defense meet, and we suggest that responses displaying defensive features should be excluded from the category of coping in accordance with the distinctions identified. [ABSTRACT FROM AUTHOR]

An abstract of the study "Atrial Fibrillation (AF) in Heart Failure Patients After Cardiac Surgery: Effect of Two-Beta-Blockers," by G. Marazzi and colleagues is presented.

Background — Current screening practices for blood donations have been successful in reducing human immunodeficiency virus (HIV) transmission through transfusion therapy. However, during the early acute phase of HIV infection the subject may harbour large amounts of highly infectious viruses without developing symptoms or detectable antigen and antibody concentrations. Thus, testing based on nucleic acid amplification technology (NAT) has been recently introduced in blood screening to shorten preseroconversion window period and to reduce the risk of virus transmission. Case Report — A volunteer blood donor was admitted in January 2000 to donate since he met the criteria for blood donor selection. The donor was found HIV repeatedly reactive by both Ab-based and NAT-based screening tests and confirmed HIV-1 positive by WB. The donor counseling allowed to identify a risk behaviour denied during the pre-donation interview. In that occasion, the donor reported that he made a check-up in May 1998, including HIV test which was negative. The check-up was just between 2 donations, one in January 1998 (HIV-1 Ab negative) and the last in January 2000 (HIVI Ab positive). It was possible to come in contact with the laboratory where the donor was checked-up and to obtain specimens, properly stored, to allow further investigations. The specimens dated respectively May 1998 and January 2000 were tested by 3[sup rd] generation (MEIA Abbott and TETRA ELISA Biotest) and new generation combined Ag/Ab (Enzygnost HIV Integral Dade Behring) immunoenzymatic tests, WB (Genelabs Diagnostics HIV Blot 2.2) and RT-PCR (Cobas HIV-1/HCV Ampliscreen Roche Diagnostic). The specimen dated May 1998 was found EIA negative, WB very faint and RTPCR positive. The results suggest that in May 1998 the donor was in the window period of HIV-1 infection, likely at very early seroconversion phase not detected by the routinely used screening/diagnostic tests, with the exception of the high sensitive genomic amplification based tests. Conclusions — The case reported here suggests that, nevertheless the strict protocols for donor selection, the prevention of viral transmissible disease in the transfusion setting relies on the blood donation screening. The introduction of technology with increased sensitivity, such as genomic screening, could really add safety to transfusion therapy. [ABSTRACT FROM AUTHOR]

An abstract of the article "Effects of six months testosterone supplementation in elderly female patients with chronic heart failure," by G. Caminiti and colleagues is presented.

Caveolin-1 is a molecular scaffold involved in lipid raft organization in several cell types. It has been implicated in protein and membrane trafficking, cytoskeletal reorganization, and regulation of signal transduction. Despite initial reports suggesting that caveolin-1 is not present in lymphocytes, we have recently identified caveolin-1 expression in murine T cells through Western blot analyses of lysates from purified primary T cell populations. In addition, we show that caveolin-1 regulates TCR/CD28 induced CD8+ T cell activation. CD8+ T cells from caveolin-1 deficient mice hypoproliferate and undergo fewer cell divisions in response to TCR/CD28 engagement and antigen:APC stimulation relative to wildtype littermates. In addition, CD8+ cells from caveolin-1 deficient mice have reduced cell survival when compared to those from wildtype mice after stimulation. Indeed, CD8+ T cells from caveolin-1 deficient mice had a lower percentage of live cells after 48 and 72 hours of stimulation and a higher number of cells undergoing apoptosis. Further, overexpression of caveolin-1 in a T cell hybridoma line increased NFAT activity in a dose dependent manner. These data suggest an important role for caveolin-1 as a positive regulator of T cell activation and cell survival. TT is predoctoral trainee recipient of the Microbial Pathogenesis Training Grant 2-T32-AI-07323. [ABSTRACT FROM AUTHOR]

An abstract of the study "Testosterone Predicts Low Functional Capacity and Morbility in Male Patients With Chronic Heart Failure," by G. Rosano and colleagues is presented.

Background mdash; Nucleic acid amplification based tests (NATs) in blood screening has the potential to identify infectious units that escape detection by the current Ab and Ab/Ag based tests, because these technologies combine the advantages of direct detection of viruses with a sensitivity several fold higher than that of the traditional methods. Commercially multiplex NAT assays, designed to detect HCV and HIV, are currently available. Validation of these analytical procedures is an advisable step before their implementation on routine use. Eventhough when commercial kits are used some validation points are already covered by the kit manufacturer, validation of the assays with regard to the most important characteristics of specificity, robustness and sensitivity has to be demonstrated by the users. Study design — Transcription mediated amplification (TMA) based NAT assay (Chiron Gen Probe) was validated for HCV and HIV-1 detection according to protocol of the European Guidelines PA/PH/OMCL(98),22 to determine the cut-off point, defined as 95% detection limit (DL) of the assay, and the robustness in term of cross-contamination. The ISS HCV-RNA 0498 (calibrated against WHO 1[sup st] HCV-RNA International Standard) and the WHO 1[sup st] International Standard for HIV-1 RNA (NIBSC 97/656) were used at the following concentrations: 31.7, 10, 3.17 1 IU/ml. 24 replicates of each dilution were tested and the DL was calculated by Probit analysis. WHO HIV-1 RNA standard spiked with ISS HCV-RNA 0498 and Multiplex 97/544 (NIBSC) were tested at different concentrations to verify the capacity of the assay to reveal both the viruses in the same specimen. Results — DL: HCV-RNA8 IU/ml HIV-1 RNA14 IU/ml. No Cross-contamination was observed by testing a panel of alternate HCVRNA or HIV-1 RNA positive and negative samples. Very low concentrations of HCV-RNA and HIV1-RNA were detectable by HIV-1/HCV assay and confirmed by the individual discriminatory HCV or HIV1 assay either in Multiplex or in the WHO HIV1 RNA plus 0498 HCV-RNA preparations. Conclusions — The development of NAT assays from separate to multiplex detection of viruses could result in a decrease of virus-specific sensitivity. In our hands the TMA designed by GenProbe to detect both HCV and HIV-1 was found a test with a very high sensitivity for the detection of both the viruses HCV and HIV-1. Therefore the assay is applicable to the screening of large numbers of blood units either testing mini pools or individual samples. [ABSTRACT FROM AUTHOR]

Aim: Current diagnostic systems, DSM-5 and ICD-10, still adopt a categorical approach to classify psychotic disorders. The present study was aimed at investigating the structure of psychotic symptomatology in both affective and non-affective psychosis from a dimensional approach., Methods: Participants with a first episode psychosis (FEP) were recruited from a cluster-randomized controlled trial (GET-UP PIANO TRIAL), offered to all Community Mental Health Centres (CMHCs) located across two northern Italian regions. After clinical stabilization, patients were assessed with a comprehensive set of psychopathological measures including the Positive and Negative Syndrome Scale, the Hamilton Depression Rating Scale and the Bech-Rafaelsen Mania Rating Scale. A two-step cluster analysis was performed., Results: Overall, 257 FEP patients (male, n = 171, 66.5%; mean age = 24.96 ± 4.56) were included in the study. The cluster analysis revealed a robust four-cluster solution: delusional-persecutory (n = 82; 31.9%), depressed (n = 95; 37%), excited (n = 26; 10.1%) and negative-disorganized (n = 54; 21%), thus suggesting a quadripartite structure with both affective and non-affective dimensions. Among non-affective dimensions, negative and disorganization symptoms constituted a unique construct apart from positive symptoms., Conclusions: Symptom dimensions may represent a useful tool for dissecting the indistinct and non-specific psychopathology of FEP in order to better target specific interventions., (© 2019 John Wiley & Sons Australia, Ltd.)

A total of 3,868 urban policemen in Rome were investigated through a historical cohort study with emphasis on mortality from cardiovascular disease and cancer. Overall mortality from cardiovascular disease, respiratory conditions, digestive and genitourinary diseases, and accidents was lower than expected. An excess risk of ischemic heart disease was observed among subjects aged less than 50 years [14 deaths, standardized mortality ratio (SMR = 1.63), 95% CI = 0.89-2.73], corresponding to workers with a short duration of employment and a short latency since first employment. Overall cancer mortality was as expected and no excess was found for lung cancer (82 deaths, SMR = 1.05). Increased mortality was observed from colon cancer (16 deaths, SMR = 1.47), melanoma (four deaths, SMR = 2.34), bladder cancer (13 deaths, SMR = 1.27), renal cancer (seven deaths, SMR = 1.39), and non-Hodgkin's lymphoma (six deaths, SMR = 1.51), although none of the excesses were statistically significant. Two deaths from male breast cancer (SMR = 14.36) and three from cancer of endocrine glands were found (SMR = 3.44). Nested case-control studies were conducted to evaluate cancer mortality risk by job category. Bladder cancer was significantly increased among car drivers (OR = 4.17); for kidney cancer, an increased odds ratio (OR = 2.27) was found among motorcyclists; non-Hodgkin's lymphoma clustered among motorcyclists (OR = 5.14). In summary, excess risk for specific cancer sites (colon, male breast, and endocrine glands) might be linked to occupational exposures; professional drivers seem to be at higher risk of bladder cancer, kidney cancer, and non-Hodgkin's lymphoma.