Axial anatomy of the leaf midrib provides new insights into the hydraulic architecture and cavitation patterns of Acer pseudoplatanus leaves

The structure of leaf veins is typically described with a hierarchical scheme (e.g. midrib, 1st order, 2nd order), that is used to predict variation in conduit diameter from one order to another overlooking possible variation within the same order. We tested whether xylem conduit diameter changes within the same vein order, with consequences on resistance to embolism. We measured the hydraulic diameter (Dh), and number of vessels (VNo) along the midrib and petioles of Acer pseudoplatanus leaves. We estimated the leaf area supplied (LAsup) at different points of the midrib and how variation in anatomical traits affected embolism resistance. Our results showed that Dh scales with distance from the midrib tip (L) with a power of 0.42, and that VNo scales with LAsup with a power of 0.66. Total conductive area scales isometrically with the LAsup. Embolism events along the midrib occurred first in the basipetal part and afterwards at the leaf tip where vessels are narrower. The distance from the midrib tip well predicts the variations in vessels diameter along the 1st order vein in sycamore maple leaves and this anatomical pattern seems to have an effect on hydraulic safety since wider vessels at the leaf base embolize first

Cost-effectiveness analysis of initial HIV treatment under Italian guidelines

INTRODUCTION: Since the mid-1990s, highly active antiretroviral therapy (HAART) has modified the clinical course of human immunodeficiency virus (HIV) infection, reducing the rate of disease progression, the incidence of opportunistic infections, and mortality. The authors of this paper performed an economic analysis to estimate the cost-effectiveness of the HAART regimens in Italy for managing HIV-infected patients according to national guidelines. PATIENTS AND METHODS: The incremental cost-effectiveness analysis was carried out by means of a Markov model, which through a decision-analytic approach, made it possible to compare the studied antiretroviral regimens. The population considered in the model consisted of adult subjects with HIV who received antiretroviral HAART treatment for the first time. The population considered in the analysis reflects the patients' characteristics according to one of the regional surveillance systems HIV/AIDS infection report currently operating in Italy. The analysis was carried out from the point of view of the Italian health care system. The considered outcome measures were quality-adjusted life years (QALYs) and direct health costs calculated for the year 2010. Both the outcomes (QALYs) and the costs were discounted by 3.5%. The time horizon adopted in the model was 10 years. RESULTS: The model shows, in terms of cost per gained QALY, single tablet regimen (STR) appeared to be the most cost-effective therapeutic choice (22,017), followed by tenofovir (TDF) + lamivudine + efavirenz (EFV) (24,526), and TDF/emtricitabine (FTC) + nevirapine (26,416), and TDF + FTC + EFV (26,558); the remaining strategies have an incremental cost-effectiveness ratio (ICER) value varying from 28,000 to 41,000 per QALY. The sensitivity analysis on the main variables confirmed the validity of the base case scenario. CONCLUSION: STR is the most cost-effective treatment strategy, compared with the other therapeutic regimens recommended by the Italian guidelines. All the ICER values of the various regimens considered by the Italian guidelines were lower than the threshold value of 50,000 commonly accepted at the international level. The model developed represents a tool for policy makers and health care professionals to make short- and long-term cost projections and thus evaluate their impact on the available budgets for HIV patients

Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-Week results of a randomized trial

Objectives Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48. Methods Patients on 3-drug ART with stable HIV-1 RNA <50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm).Results In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm. Conclusion Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therap

Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-Week results of a randomized trial

Objectives: Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48. Methods: Patients on 3-drug ART with stable HIV-1 RNA <50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm). Results: In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm. Conclusion: Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therapy

Emotions may influence the production of pro-inflammatory cytokines in HIV positive individuals

Rationale : Emotions have been associated with production of pro-inflammatory cytokines such as TNF-alpha and IL-6; more precisely, negative emotions with greater cytokines level whereas positive emotions with lower level of pro-inflammatory cytokines. This may have significant repercussions on individuals’ health specifically for those who are subjected to chronic inflammation as in the case of HIV positive persons. In fact, HIV virus itself produces greater TNF-alpha production, which in its turns might promote greater IL-6 levels. Thus, this work was conducted in order to verify whether along with HIV association with pro-inflammatory cytokines production, negative and positive emotions, as well as their “balance”, might be associated with cytokines level. Methods : Participants to this cross-sectional study were 90 individuals with HIV diagnosis. Emotions were assessed through the Italian version of Derogatis Affects Balance Scale edited by the first two authors of this work. The biomarkers included were viral load, TNF-alpha, and IL-6. Individuals also self-reported whether they were under antiretroviral therapy. Results : A Structural Equation Model was performed in order to test if negative and positive emotions and their balance (that consisted in the ratio of positive/negative emotions) along with viral load were associated with cytokines level. Results indicated that viral load (β = 0.538, p<0.001), negative emotions (β = 0.366, p<0.05) and positive/negative emotions (β = − 0.420, p<0.05) ratio were significantly associated with greater TNF-alpha production. No significant associations were observed with IL-6. Conclusion : Taken together, these results may indicate that together with virus effect in producing greater inflammation, emotions may also contribute to it. Negative emotions could then promote greater inflammation whereas, when individuals experience more positive emotions than negative, inflammation might be reduced

Supplementary Figure and table

Supplementary Figure and table of the paper "<b><i>Switching between swimming states in rotifers – case study </i></b><b>Keratella cochlearis</b>" by Obertegger et al. in Marine and Freshwater Behaviour and Physiolog

R skript of the steps involved in analysing trajectories of rotifers

steps involved in analysing trajectories of rotifers as explained in the paper "<b><i>Switching between swimming states in rotifers – case study </i></b><b>Keratella cochlearis</b> " by Obertegger et al. in Marine and Freshwater Behaviour and Physiolog

males of K. cochlearis as identified by BEMOVI (overlay)

males of K. cochlearis as identified by BEMOVI (overlay) - <div><b><i>Switching between swimming states in rotifers – case study </i></b><b>Keratella cochlearis</b>" by Obertegger et al. in Marine and Freshwater Behaviour and Physiology<br></div

Tenofovir-induced renal toxicity in 324 HIV-infected, antiretroviral-naive patients.

To better evaluate the renal safety profile of tenofovir, we performed a retrospective study of HIV-infected antiretroviral-naïve patients starting a first antiretroviral therapy between July 2004 and July 2008, and followed-up for 24 months. The glomerular filtration rate (GFR) was calculated using the MDRD formula, and tubular dysfunction was diagnosed with 2 or more of the following: proteinuria, glucosuria, hypouricemia, hypophosphatemia and hypokalemia. Overall, 324 patients were enrolled: 201 were tenofovir-exposed and were compared with 123 tenofovir-unexposed subjects. In both the unadjusted and adjusted analyses, tenofovir-exposed subjects had a significantly greater decline in GFR and a significantly higher incidence of proximal tubular dysfunction through 24 months. Reduced glomerular and tubular functions were significantly associated with older age, diabetes, hypertension and concomitant therapy with a protease inhibitor

Prevalence of sub-clinical vertebral fractures in HIV-infected patients

Although the increased prevalence of low bone mineral density among HIV-infected patients has raised concern for increased fracture risk, few investigations have evaluated fracture rates. Increasing evidence indicates that HIV patients are at higher risk of osteoporotic fractures compared to the general population. This is a very important issue, because fragility fractures are complications with a significant prognostic value. Our study performed lateral spine X-ray to assess the prevalence of sub-clinical vertebral fractures in 202 HIV patients. Factors associated with vertebral fractures were also investigated. The prevalence of vertebral fractures was significantly high (23.3%): 14 subjects had SDI (spine deformity index)= 1, 22 SDI=2-3 and 11 SDI >4. Differences in the prevalence of vertebral fractures between naive and ART experienced patients was 18% vs. 24%, respectively. Furthermore, patients had a high prevalence of severe and multiple fractures; in 19 patients (40%) fractures involved multiple vertebrae. Patients with vertebral fractures were significantly older, with renal insufficiency and steroid use more frequently than subjects with no fractures. Our data suggest that the prevalence of vertebral fractures in HIV infection may be higher than expected, and lateral spine X-ray has a role in the screening of bone disease, at least in patients with a significant risk of fragility fractures