Low serum phosphate levels are related to increased cardiovascular risk in HIV-1 infected patients

Purpose of the study Hypophosphatemia may contribute directly to the devel- opment of obesity, hypertension and dyslipidemia. Hyperglycemia, insulin resistance, hyperlipidemia and hypertension, which are components of metabolic syn- drome, are also recognized as strong risk factors for car- diovascular disease [1]. This study was performed to determine whether serum phosphate levels are asso- ciated with increased risk for cardiovascular events. Methods We enrolled 125 consecutive HIV-1-infected patients in a cross-sectional study. All patients were receiving highly active antiretroviral therapy (HAART) for more than six months. Fasting phosphate, lipids (cholesterol, HDL, triglycerides), Homeostasis Model Assessment (HOMA), blood pressure were evaluated. Framingham 10 years risk of general cardiovascular disease was used to assess three cardiovascular risk (CVR) categories (low CVR 20%). Summary of results We observed a statistically significant decrease in serum phosphate levels in the three different CVR groups (low risk: 3.5 mg/dl; medium risk: 3.3 mg/dl; high risk: 2.9 mg/dl; p=0.001). There was a strong negative correlation between Framingham score and phosphate levels (r:- 0.37, p<0.0001). Figure 1 Multiple regression analysis, including age, months of HAART, CD4 cells count, cholesterol, HDL, HOMA, systolic pressure, months of Tenofovir use, showed that only HOMA (r:-0.30, p<0.01) and age (r:-0.3, p<0.01) were the most important determinants of serum phos- phate values. Conclusions We found that lower phosphate level is correlated with cardiovascular risk and insulin resistance. Therefore, when serum phosphate levels are too low the patients is at risk for cardiovascular events and/or metabolic syndrome

Liquid filled canyons on Titan

In May 2013 the Cassini RADAR altimeter observed channels in Vid Flumina, a drainage network connected to Titan’s second largest hydrocarbon sea, Ligeia Mare. Analysis of these altimeter echoes shows that the channels are located in deep (up to ~570 m), steep-sided, canyons and have strong specular surface reflections that indicate they are currently liquid filled. Elevations of the liquid in these channels are at the same level as Ligeia Mare to within a vertical precision of about 0.7 m, consistent with the interpretation of drowned river valleys. Specular reflections are also observed in lower order tributaries elevated above the level of Ligeia Mare, consistent with drainage feeding into the main channel system

The 5'-3' exoribonuclease Pacman (Xrn1) regulates expression of the heat shock protein Hsp67Bc and the microRNA miR-277-3p in Drosophila wing imaginal discs

Pacman/Xrn1 is a highly conserved exoribonuclease known to play a critical role in gene regulatory events such as control of mRNA stability, RNA interference and regulation via miRNAs. Although Pacman has been well studied in Drosophila tissue culture cells, the biologically relevant cellular pathways controlled by Pacman in natural tissues are unknown. This study shows that a hypomorphic mutation in pacman (pcm5) results in smaller wing imaginal discs. These tissues, found in the larva, are known to grow and differentiate to form wing and thorax structures in the adult fly. Using microarray analysis, followed by quantitative RT-PCR, we show that eight mRNAs were increased in level by >2 fold in the pcm5 mutant wing discs compared to the control. The levels of pre mRNAs were tested for five of these mRNAs; four did not increase in the pcm5 mutant, showing that they are regulated at the post-transcriptional level and therefore could be directly affected by Pacman. These transcripts include one that encodes the heat-shock protein Hsp67Bc, which is upregulated 11.9-fold at the post-transcriptional level and 2.3-fold at the protein level. One miRNA, miR-277-3p, is 5.6-fold downregulated at the post-transcriptional level in mutant discs, suggesting that Pacman affects its processing in this tissue. Together, these data show that a relatively small number of mRNAs and miRNAs substantially change in abundance in pacman mutant wing imaginal discs. Since Hsp67Bc is known to regulate autophagy and protein synthesis, it is possible that Pacman may control the growth of wing imaginal discs by regulating these processes

Xrn1/Pacman affects apoptosis and regulates expression of hid and reaper

Programmed cell death, or apoptosis, is a highly conserved cellular process that is crucial for tissue homeostasis under normal development as well as environmental stress. Misregulation of apoptosis is linked to many developmental defects and diseases such as tumour formation, autoimmune diseases and neurological disorders. In this paper, we show a novel role for the exoribonuclease Pacman/Xrn1 in regulating apoptosis. Using Drosophila wing imaginal discs as a model system, we demonstrate that a null mutation in pacman results in small imaginal discs as well as lethality during pupation. Mutant wing discs show an increase in the number of cells undergoing apoptosis, especially in the wing pouch area. Compensatory proliferation also occurs in these mutant discs, but this is insufficient to compensate for the concurrent increase in apoptosis. The phenotypic effects of the pacman null mutation are rescued by a deletion that removes one copy of each of the pro-apoptotic genes reaper, hid and grim, demonstrating that pacman acts through this pathway. The null pacman mutation also results in a significant increase in the expression of the pro-apoptotic mRNAs, hid and reaper, with this increase mostly occurring at the post-transcriptional level, suggesting that Pacman normally targets these mRNAs for degradation. Our results uncover a novel function for the conserved exoribonuclease Pacman and suggest that this exoribonuclease is important in the regulation of apoptosis in other organisms

Movies, ethics and accounting: a teaching experience

This research presents an innovative learning experience undertaken in three groups of a financial accounting course at the University of Valencia (Spain). After watching three accountingrelated movies, students answered a test based on each movie with questions about the ethical and accounting issues described in them and their satisfaction with the learning technique. Nonparametric tests and a multivariate analysis showed that the students who participated in this experience obtained a higher exam mark than those who did not. Our results evidence a significant effect on the final exam mark for more questions only in one of the movies. Our results are valuable because they show that students engage in this methodological approach, which can be helpful for them to improve their exam performance

Human metapneumovirus and human bocavirus associated with respiratory infection in Apulian population

AbstractWe have studied the occurrence of hBoV, hMPV and InfA-B in an Apulian population with respiratory tract infections. During influenza season 2008–2009, 116 oropharingeal swabs were collected from patients affected by Influenza-Like Illness (ILI). The PCR products of hMPV M and HBoV NP-1 genes were sequenced. 78 out of 116 samples were positive for at least one respiratory virus; hBoV was detected in 53, hMPV in 22 and InfA-B in 41 out of 116 swabs. A high rate of hBoV infection in adult (18.9%) and elderly (26.4%) subjects was found. The co-infection rate was higher for hMPV (18/22 cases, 81.8%) compared to hBoV (26/53 cases, 49.1%), and InfA-B (25/41 cases, 61.0%). Co-infections were common in children. hBoV positive samples shared a high level of genetic similarity with the hBoV1 genotype, and hMPV positive samples clustered with A2 subgroup. Our results suggest that hBoV and hMPV play a role in ILI

Kidney tubular function and serum phosphate levels in HIV-1-infected patients treated with tenofovir: preliminary results

Purpose of the study There is concern that human immunodeficiency virus (HIV) infection and the use of highly active antiretro- viral therapy lead to cumulative toxicity. Tenofovir (TDF) is the first choice for most subjects. Even if it has a safe metabolic profile, much attention has been fixed on kidney tubular function and regulation of phosphate metabolism. We performed this study to evaluate the role of a TDF based regimen has on renal tubular over time. Methods Prospective, cross-sectional, single centre study was car- ried out. 121 HIV-1-infected patients were consecutively enrolled in six groups based on duration of TDF exposi- tion: G0, from 6 to 12 months; G1 from 13 to 24 months; G2 from 25 to 36 months; G3 from 37 to 48 months; G4 more than 48 months and G5 under HAART but never exposed to TDF. Glomerular func- tion was assessed using creatinine clearance (CrCL) cal- culated by MDRD. Tubular function was assessed using fractional excretion ratio of phosphate and normalized renal threshold phosphate concentration. Demographic, CD4, serum phosphate levels, viral load were collected. Summary of results A total of 121 consecutive HIV-1-infected patients were analyzed: 15 in G0, 11 in G1, 14 in G2, 32 in G3, 35 in G4 and 14 in G5. Mean of TDF exposure was 10.26, 21.4, 36.2, 47.3 and 67.4 months in G0, G1, G2, G3 and G4 respectively. There was no statistically significant dif- ference of mean values of FEP(11.2, 10.3, 8.4, 9.8, 11.1 and 10% in G0, G1, G2, G3, G4 and G5 respectively), TmPO4/GFR (3.5, 3.5, 3.6, 3.6, 3.4 and 3.4 mg/dl in G0, G1, G2, G3, G4 and G5 respectively ), CrCL (102.2, 94.3, 92.9, 106.5, 103.1 and 101.6 ml/min/1.73m2 in G0, G1, G2, G3, G4 and G5 respectively) and serum phos- phate levels (3.4, 3.3, 3.1, 3.5, 3.3 and 3.4 in G0, G1, G2, G3, G4 and G5 respectively) between groups. Moreover, we did not find correlation of FEP (r:0.04, p:0.6) and TmPO4/GFR (r:0.05, p:0.5) with duration of TDF therapy. Conclusions Treatment with TDF is not associated with altered kid- ney tubular function and serum phosphate levels over time

Altered phosphate metabolism in HIV-1-infected patients: another feature of metabolic syndrome?

Purpose of the study Metabolic syndrome represent a cluster of cardiovascu- lar risk factors that has become a serious problem for HIV-1-infected patients. It was proposed that distur- bances in phosphate metabolism may represent a key feature of metabolic syndrome. Because phosphate is involved directly in carbohydrate metabolism, hypopho- sphatemia can results in impaired utilization of glucose, insulin resistance and hyperinsulinemia. Thus, we undertook the present study to investigate the relation- ship between phosphate levels and the presence of the characteristics of metabolic syndrome, as well as the mechanism that may be responsible for reduced phos- phate levels in patients with this syndrome. Methods 130 HIV-1-infected patients were consecutively enrolled in a prospective, cross-sectional, single centre study. All patients were receiving HAART for more than six months. We selected two groups: HIV+ patients with metabolic syndrome (group A, n=86) and HIV+ patients without metabolic syndrome (group B, n=44). The diag- nosis of metabolic syndrome was based on Adult Treat- ment Panel III guidelines. Demographic characteristics, metabolic variables, duration of Tenofovir therapy, dura- tion of HAART, CD4 and viral load were collected. Kid- ney tubular function was examined using tubular resorption of phosphate and normalized renal threshold phosphate concentration. Summary of results Patients with metabolic syndrome showed significantly lower phosphate (3.13 mg/dl vs 3.55 mg/dl, p<0.01) and higher insulin (13.2 mg/dl vs 6.9 mg/dl, p<0.01) levels compared with controls. There was a linear significant decrease in phosphate values as the number of compo- nents of metabolic syndrome increased (p<0.001). Multi- ple regression analysis including all 5 components of metabolic syndrome and months of TDF treatment showed that insulin level was the most discriminant of serum phosphate (r= -0.22, p<0.01). Figure 1 Conclusions Our preliminary data demonstrated that HIV-1-infected patients with metabolic syndrome showed significantly lower phosphate levels compared with HIV-1-infected patients without metabolic syndrome regardless of teno- fovir based therapy. The clinical significance of these disturbances, as well as their importance as target for preventive or therapeutic interventions, remains to be established

HIV infection and frequency of micronucleus in human peripheral blood cells

Purpose. People living with HIV have higher rates of malignancies than the general population in the era of active antiretroviral therapy (ART). Genotoxic effects of HIV infection and/or ART that can induce neoplastic development are not yet well known. A prospective cohort study to investigate DNA damage measured through the micronuclei (MN) frequency in HIV-patients has been performed. Methods. Peripheral blood mononuclear cells (PBMC) were isolated from 52 HIV-patients treated with ART and 55 healthy controls. Results. By the comparison of MN frequency, a significant difference between HIV-patients (15.5 ± 9.8) and controls (6.0 ± 3.6) (p < 0.001) has been revealed. In univariate linear regression analysis, HCV infection (r = 0.31; p < 0.001), HIV-RNA (r = 0.29; p < 0.03) and duration of infection (r = - 0.16; p < 0.25) were associated with MN frequency; while only viral load (VL) significantly correlates (r = 0.29; p < 0.05) in a multiple regression model. Conclusions. The association of VL with MN frequency supports a genotoxic effect of HIV infection