Marta Di Nicola

Prognostic Value of Different Indices of Blood Pressure Variability in Hypertensive Patients

BACKGROUND The independent prognostic significance of different indices of blood pressure (BP) variability is not clear. We investigated the prognostic value of BP variability estimated as s.d. or average real variability (ARV) of daytime and night time BP, in hypertensive patients. METHODS The occurrence of fatal and nonfatal cardiovascular events was evaluated in 1,280 sequential hypertensive patients (550 initially untreated and 730 initially treated) aged > or =40 years. Subjects with s.d. or ARV of daytime or night time systolic or diastolic BP below or above the median were classified as having low or high BP variability. RESULTS During the follow-up (4.75 +/- 1.8 years), 104 cardiovascular events occurred. The event rate per 100 patient-years was 1.71 in the global population. After adjustment for other covariates, Cox regression analysis showed that cardiovascular risk was higher in subjects with high ARV of daytime systolic BP in initially untreated, initially treated, and all the subjects (high vs. low ARV, hazard ratio (HR) 2.29 (1.06-4.94), HR 1.90 (1.06-3.39), and HR 2.07 (1.31-3.28), respectively). ARV of daytime diastolic BP and night time BP, and s.d. of daytime and night time BP were not significantly associated with risk or were not independent predictors of outcome. CONCLUSIONS In this study, high ARV of daytime systolic BP resulted in an independent predictor of cardiovascular risk in hypertensive patients, while high s.d. did not. Our data suggest that, in comparison to s.d., ARV could be a more appropriate index of BP variability and a more useful predictor of outcomes.

microRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer.

Introduction: Lung cancer is the highest cause of mortality among tumor pathologies worldwide. There are no validated techniques for an early detection of pulmonary cancer lesions other than low-dose helical computed tomography scan. Unfortunately, this method has some negative effects. Recent studies have laid the basis for development of exosomes-based techniques to screen/diagnose lung cancers. As the isolation of circulating exosomes is a minimally invasive procedure, this technique opens new possibilities for diagnostic applications. Methods: We used a first set of 30 plasma samples from as many patients, including 10 patients affected by lung adenocarcinomas, 10 with lung granulomas, and 10 healthy smokers matched for age and sex as negative controls. Wide-range microRNAs analysis (742 microRNAs) was performed by quantitative real time polymerase chain reaction. Data were compared on the basis of lesion characteristics, using WEKA software for statistics and modeling. Subsequently, selected microRNAs were evaluated on an independent larger group of samples (105 specimens: 50 lung adenocarcinomas, 30 lung granulomas, and 25 healthy smokers). Results: This analysis led to the selection of four microRNAs to perform a screening test (miR-378a, miR-379, miR-139-5p, and miR-200b-5p), useful to divide population into two groups: nodule (lung adenocarcinomas + carcinomas) and non-nodule (healthy former smokers). Six microRNAs (miR-151a-5p, miR-30a-3p, miR-200b-5p, miR-629, miR-100, and miR-154-3p) were selected for a second test on the nodule population to discriminate between lung adenocarcinoma and granuloma. Conclusions: The screening test showed 97.5% sensitivity, 72.0% specificity, and area under the curve receiver operating characteristic of 90.8%. The diagnostic test had 96.0% sensitivity, 60.0% specificity, and area under the curve receiver operating characteristic of 76.0%. Further evaluation is needed to confirm the predictive power of these models on larger cohorts of samples.

LIMPIC: a computational method for the separation of protein MALDI-TOF-MS signals from noise

BackgroundMass spectrometry protein profiling is a promising tool for biomarker discovery in clinical proteomics. However, the development of a reliable approach for the separation of protein signals from noise is required. In this paper, LIMPIC, a computational method for the detection of protein peaks from linear-mode MALDI-TOF data is proposed. LIMPIC is based on novel techniques for background noise reduction and baseline removal. Peak detection is performed considering the presence of a non-homogeneous noise level in the mass spectrum. A comparison of the peaks collected from multiple spectra is used to classify them on the basis of a detection rate parameter, and hence to separate the protein signals from other disturbances.ResultsLIMPIC preprocessing proves to be superior than other classical preprocessing techniques, allowing for a reliable decomposition of the background noise and the baseline drift from the MALDI-TOF mass spectra. It provides lower coefficient of variation associated with the peak intensity, improving the reliability of the information that can be extracted from single spectra. Our results show that LIMPIC peak-picking is effective even in low protein concentration regimes. The analytical comparison with commercial and freeware peak-picking algorithms demonstrates its superior performances in terms of sensitivity and specificity, both on in-vitro purified protein samples and human plasma samples.ConclusionThe quantitative information on the peak intensity extracted with LIMPIC could be used for the recognition of significant protein profiles by means of advanced statistic tools: LIMPIC might be valuable in the perspective of biomarker discovery.

Dysregulation of chemo-cytokine production in schizophrenic patients versus healthy controls

BackgroundThe exact cause of schizophrenia is not known, although several aetiological theories have been proposed for the disease, including developmental or neurodegenerative processes, neurotransmitter abnormalities, viral infection and immune dysfunction or autoimmune mechanisms. Growing evidence suggests that specific cytokines and chemokines play a role in signalling the brain to produce neurochemical, neuroendocrine, neuroimmune and behavioural changes. A relationship between inflammation and schizophrenia was supported by abnormal cytokines production, abnormal concentrations of cytokines and cytokine receptors in the blood and cerebrospinal fluid in schizophrenia. Since the neuropathology of schizophrenia has recently been reported to be closely associated with microglial activation we aimed to determined whether spontaneous or LPS-induced peripheral blood mononuclear cell chemokines and cytokines production is dysregulated in schizophrenic patients compared to healthy subjects. We enrolled 51 untreated first-episode schizophrenics (SC) and 40 healthy subjects (HC) and the levels of MCP-1, MIP-1α, IL-8, IL-18, IFN-γ and RANTES were determined by Elisa method in cell-free supernatants of PBMC cultures.ResultsIn the simultaneous quantification we found significantly higher levels of constitutively and LPS-induced MCP-1, MIP-1α, IL-8 and IL-18, and lower RANTES and IFNγ levels released by PBMC of SC patients compared with HC. In ten SC patients receiving therapy with risperidone, olanzapine or clozapine basal and LPS-induced production of RANTES and IL-18 was increased, while both basal and LPS-induced MCP-1 production was decreased. No statistically significant differences were detected in serum levels after therapy.ConclusionThe observation that in schizophrenic patients the PBMC production of selected chemo-cytokines is dysregulated reinforces the hypothesis that the peripheral cyto-chemokine network is involved in the pathophysiology of schizophrenia. These preliminary, but promising data are supportive of the application of wider profiling approaches to the identification of biomarker as diagnostic tools for the analysis of psychiatric diseases.

Visual performance and biocompatibility of 2 multifocal diffractive IOLs: six-month comparative study.

PURPOSE: To evaluate the distance and near functional capacity, wavefront error and biocompatibility in patients with 2 diffractive multifocal intraocular lenses (MIOLs). SETTING: Ophthalmology Department of Chieti‐Pescara University (Italy). METHODS: This prospective study comprised 28 eyes of 28 senile cataract patients having phacoemulsification and implantation of the Tecnis ZM900 MIOL (Group 1) and the AcrySof ReSTOR MIOL (Group 2). The main outcome measures, over a 6‐month follow‐up period, were spherical equivalent, distance visual acuity at high and low contrast, near visual acuity, and defocus curve. Wavefront error was evaluated in both groups. Capsule opacification was also assessed. RESULTS: The high and low contrast uncorrected and best corrected visual acuity for distance did not show statistically significant differences between the 2 groups. The distance corrected near visual acuity was 1.86 ± 1.66 in Group 1 and 1.93 ± 1.12 in Group 2. The depth of focus was 4.5 diopters in both groups. The root mean square of total aberration and of spherical and coma aberrations were significantly lower in Group 1 than in Group 2. A higher percentage of patients with Tecnis MIOLs showed a more severe grade of anterior fibrosis. Posterior opacification was minimal and not significantly different between the 2 groups. CONCLUSION: Diffractive MIOLs were effective in improving functional capacity for distance and near and provided a good quality of vision due to a significant reduction in spherical aberration, particularly in the Tecnis MIOLs. The higher capsular biocompatibility of the ReSTOR MIOL compared with the Tecnis MIOL could ensure long‐term stability.

Relation between pro-inflammatory cytokines and acetylcholine levels in relapsing-remitting multiple sclerosis patients.

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disorder. Since acetylcholine (ACh) is known to participate in the inflammatory response, we investigated the possible relationship between pro-inflammatory cytokines and acetylcholine levels in relapsing-remitting multiple sclerosis (RR-MS) patients. Levels of ACh and pro-inflammatory cytokines IL1-β and IL-17 were measured both in cerebrospinal fluid (CSF) and sera of 22 RR-MS patients in the relapsing phase and in 17 control subjects affected by other non-neurological diseases (OND). We observed higher levels of pro-inflammatory cytokines such as IL-1β and IL-17 in both CSF and serum of RR-MS patients compared to control subjects. Moreover, ACh levels were lower in CSF and serum of RR-MS patients compared to levels of control subjects. Although the relationship between high inflammatory cytokine levels and low ACh levels need to be further investigated in the future, our data suggest that IL-1β, and cytokines induced by it, such as IL-17 and ACh, may be involved in the pathogenesis of MS.

Improved metabolic profile after switch to darunavir/ritonavir in HIV positive patients previously on protease inhibitor therapy.

Metabolic abnormalities associated with cumulative exposure to antiretroviral therapy have been linked to an increased risk of myocardial infarction in HIV positive individuals. The aim of this study was to evaluate whether the switch from lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) to darunavir/ritonavir (DRV/r) is able to improve the lipid profile. A total of 13 Caucasian subjects (7 from LPV/r and 6 from FPV/r) were enrolled in the study and received DRV/r at the dose of 800/100 mg, without change in their NRTI backbone. Viro‐immunological parameters, triglycerides (TGs), total cholesterol (TCh), high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) cholesterol, fasting glucose, HOMA‐IR, indexes of hepatic and renal functionality, microalbuminuria and cystatin C were measured at baseline (T0), 3 months (T3), 6 months (T6), and 12 months (T12). The switch to DRV/r reduced levels of TCh, LDL, and TGs at T3. Similar improvements were confirmed further at T6 and at T12. A 14% increase in CD4+ count cells (P < 0.05) was observed. Serum cystatin C values showed a statistically significant decrease. After 12 months of switching to DRV/r from LPV/r or FPV/r, patients infected with HIV with TGs above 200 mg/dl, showed a 49% decrease in TGs, along with a 16% reduction of LDL and 19% reduction of TCh. Switching to DRV/r also improved immunological parameters, such as CD4+ cells count and cystatin C plasmatic levels, which may translate into a reduction of the cardiovascular risk. In conclusion, a switch to DRV/r should be considered in those HIV positive patients undergoing antiretroviral therapy, who also present abnormal lipid profiles. J. Med. Virol. 85:755–759, 2013.

Hydrophobic acrylic versus heparin surface-modified polymethylmethacrylate intraocular lens: a biocompatibility study.

BackgroundThe implant of intraocular lenses (IOLs) following cataract surgery induces a foreign-body reaction to the IOL and a response on the part of the lens epithelial cells (LECs). The purpose of this study was to compare these aspects after the implantation of two different IOL materials.MethodsThirty-six cataract patients were randomised to receive two different foldable lens: an acrylic hydrophobic IOL (Acrysof MA30BA) and a heparin surface-modified (HSM) polymethylmethacrylate IOL (Pharmacia & Upjohn 809C) after phacoemulsification. Slit-lamp biomicroscopy with specular technique was used to assess the inflammatory cell adhesion on the anterior IOL surface, anterior capsule opacification (ACO) and membrane growth from the rhexis edge at 7, 30, 90, 180 and 360 days after surgery.ResultsThe 809C group showed a higher percentage of patients with slight inflammatory cell adhesion on the anterior cell surface and a higher small cellular density during the whole follow-up period. The epithelioid cell response was greater in the 809C group than the Acrysof group but the difference between the two groups was not statistically significant. The ACO increased during the follow-up in both groups but was significantly higher in the 809C group.ConclusionAcrysof lenses are more biocompatible than HSM IOLs, showing a lower grade of inflammatory cell adhesion and ACO. The implantation of these lenses may be particularly indicated in patients with pathologies predisposing to blood–aqueous barrier damage.

Effect of Probiotic Supplement on Cytokine Levels in HIV-Infected Individuals: A Preliminary Study

Inflammation persists in patients infected with HIV. Reduction of inflammatory cytokines and microbial translocation might be one way that this could be managed. Purpose: The anti-inflammatory properties of certain probiotic strains prompted us to investigate whether a probiotic could reduce the inflammatory index of HIV-infected patients. Methods: The study involved 30 HIV+ males on antiretroviral therapy, who were given one bottle of fermented milk Yakult Light® containing Lactobacillus casei Shirota (LcS) twice a day for four weeks. Results: The probiotic LcS was associated with an increase of T lymphocytes and a significant increase of CD56+ cells (p = 0.04). There was also a significant decrease of mRNA levels of TGFβ, IL-10 and IL-12 (p < 0.001) and IL-1β expression (p < 0.001) and an increase of serum IL-23 (p = 0.03). In addition, decreased inflammation and cardiovascular risk were observed, as shown by a reduction of cystatin C (p < 0.001). Conclusions: These data provide preliminary evidence that probiotic supplementation may modulate certain immunological parameters and some of the cytokines that were analyzed. Thus, we propose that LcS may be an inexpensive and practical strategy to support the immune function of HIV+ patients.

Macular Features in Retinitis Pigmentosa: Correlations Among Ganglion Cell Complex Thickness, Capillary Density, and Macular Function

Purpose To investigate correlations among macular ganglion cell complex (GCC) layer thickness, macular capillary density, and macular function in patients affected by retinitis pigmentosa (RP). Methods Fourteen patients (28 eyes) with previous diagnosis of RP were enrolled. The diagnosis of these conditions was made based on both clinical features and electrophysiological examination. All patients underwent a complete ophthalmologic examination, including optical coherence tomography angiography (OCTA) and multifocal electroretinogram (mfERG). Main outcome measures were macular GCC layer thickness; superficial capillary plexus (SCP) vessel density; deep capillary plexus (DCP) vessel density; choriocapillaris plexus (CCP) vessel density; and amplitudes of mfERG N1 and P1 waves. Results Average GCC thickness was significantly thinner in RP patients (76.0 ± 25.1 and 109.2 ± 17.5 μm, P = 0.028). Superficial capillary plexus density was 42.2 ± 3.4% in the RP group and 51.4 ± 2.3% in the control group (P < 0.001). Deep capillary plexus density was reduced in RP patients (42.7 ± 6.2%) after the comparison with healthy subjects (56.6 ± 2.2%, P < 0.001). Choriocapillaris plexus density was significantly less in RP patients than in the control group (65.3 ± 2.7% and 67.2 ± 1.4%, P = 0.024). Superficial capillary plexus and DCP density were significantly correlated with both mfERG values and GCC thickness. Conclusions We showed that both choroid and retinal vessels were modified in RP patients after comparison with healthy subjects. Moreover, we demonstrated that the SCP and DCP vessel densities are correlated with the macular function, as well as with the GCC thickness.