Bio-herbicidal potential of the essential oils from different Rosmarinus Officinalis L. chemotypes in laboratory assays

The current study aimed to assess the allelopathic effect of Rosmarinus officinalis L. essential oils (EOs) to define the potent effect against weed species, by exploring distinct chemotypes and their main compounds. The EOs from eight accessions were characterized. Their components were identified by gas chromatography, and four chemotypes were defined; C1 (α-pinene), C2 (camphor), C3 (α-pinene/1,8-cineole), and C4 (α-pinene/1,8-cineole/camphor). Four concentrations of the EOs (400, 800, 1200, and 2400 μL/L) and the main compounds of each chemotype were tested in a laboratory assay against Amaranthus retroflexus L. and Lolium perenne L. in pre-and post-germination. The results showed that the EOs significantly affected all the tested parameters (germination, early growth, and physiological and histological parameters of the weeds under study) in a dose, chemotype, and species dependent manner. A. retroflexus was more sensitive than L. perenne at germination level being significantly inhibited at the lowest dose of all the chemotypes. The latter all exhibited significant effects but with a higher potency of C2 (camphor chemotype) and C3 (α-pinene/1,8-cineole chemotype), as well qualitative differences in the induced damage. Our results thus increase knowledge about the role of the monoterpene composition in bioherbicidal effect, which can help in the development of EO based bio-herbicides

Invading parasites: spillover of an alien nematode reduces survival in a native species

It is widely assumed that spillover of alien parasites to native host species severely impacts na\uefve populations, ultimately conferring a competitive advantage to invading hosts that introduced them. Despite such host-switching events occurring in biological invasions, studies demonstrating the impact of alien macroparasites on native animal hosts are surprisingly few. In Europe, native red squirrels (Sciurus vulgaris) are replaced by introduced North American grey squirrels (S. carolinensis) mainly through resource competition, and, only in the United Kingdom and Ireland, by competition mediated by a viral disease. In Italy such disease is absent, but spillover of an introduced North American nematode (Strongyloides robustus) from grey to red squirrels is known to occur. Here, we used long-term (9 years) capture-mark-recapture and parasitological data of red squirrels in areas co-inhabited by grey squirrels in Northern Italy to investigate the impact of this alien helminth on na\uefve native squirrels\u2019 body mass, local survival, and reproduction of females. We found no negative effect of the alien parasite on body mass or reproductive success, but intensity of infection by S. robustus reduced survival of both male and female squirrels. Significantly, survival of squirrels co-infected by their native nematode, Trypanoxyuris sciuri, was less affected by S. robustus, suggesting a protective effect of the native helminth against the new infection. Hence, we demonstrate that alien S. robustus spillover adds to the detrimental effects of resource competition and stress induced by grey squirrels, further reducing the fitness of the native species in the presence of the invasive competitor

ING116070: a study of the pharmacokinetics and antiviral activity of dolutegravir in cerebrospinal fluid in HIV-1-infected, antiretroviral therapy-naive subjects.

BackgroundDolutegravir (DTG), a once-daily, human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, was evaluated for distribution and antiviral activity in cerebrospinal fluid (CSF).MethodsING116070 is an ongoing, single-arm, open-label, multicenter study in antiretroviral therapy-naive, HIV-1-infected adults. Subjects received DTG (50 mg) plus abacavir/lamivudine (600/300 mg) once daily. The CSF and plasma (total and unbound) DTG concentrations were measured at weeks 2 and 16. The HIV-1 RNA levels were measured in CSF at baseline and weeks 2 and 16 and in plasma at baseline and weeks 2, 4, 8, 12, and 16.ResultsThirteen white men enrolled in the study; 2 withdrew prematurely, 1 because of a non-drug-related serious adverse event (pharyngitis) and 1 because of lack of treatment efficacy. The median DTG concentrations in CSF were 18 ng/mL (range, 4-23 ng/mL) at week 2 and 13 ng/mL (4-18 ng/mL) at week 16. Ratios of DTG CSF to total plasma concentration were similar to the unbound fraction of DTG in plasma. Median changes from baseline in CSF (n = 11) and plasma (n = 12) HIV-1 RNA were -3.42 and -3.04 log10 copies/mL, respectively. Nine of 11 subjects (82%) had plasma and CSF HIV-1 RNA levels <50 copies/mL and 10 of 11 (91%) had CSF HIV-1 RNA levels <2 copies/mL at week 16.ConclusionsThe DTG concentrations in CSF were similar to unbound plasma concentrations and exceeded the in vitro 50% inhibitory concentration for wild-type HIV (0.2 ng/mL), suggesting that DTG achieves therapeutic concentrations in the central nervous system. The HIV-1 RNA reductions were similar in CSF and plasma. Clinical Trials Registration. NCT01499199

Fluctuation relations in non-equilibrium stationary states of Ising models

Fluctuation relations for the entropy production in non equilibrium stationary states of Ising models are investigated by Monte Carlo simulations. Systems in contact with heat baths at two different temperatures or subject to external driving will be studied. In the first case, by considering different kinetic rules and couplings with the baths, the behavior of the probability distributions of the heat exchanged in a time $\tau$ with the thermostats, both in the disordered and in the low temperature phase, are discussed. The fluctuation relation is always verified in the large $\tau$ limit and deviations from linear response theory are observed. Finite-$\tau$ corrections are shown to obey a scaling behavior. In the other case the system is in contact with a single heat bath but work is done by shearing it. Also for this system the statistics collected for the mechanical work shows the validity of the fluctuation relation and preasymptotic corrections behave analogously to the case with two baths.Comment: 9 figure

Respiratory Syncytial Virus Bronchiolitis in Infancy: The Acute Hospitalization Cost

Introduction: Respiratory syncytial virus (RSV) bronchiolitis is among the leading causes of hospitalization in infants. Prophylaxis with palivizumab may reduce RSV infection, but its prescription is restricted to high-risk groups. The aim of the study is to retrospectively determine acute hospitalization costs of bronchiolitis. Materials and methods: Infants aged 1 month-1 year, admitted to Bambino Gesu Children Hospital, Rome, Italy, with a diagnosis of bronchiolitis from January 1 till December 31, 2017, were included in the study. Results: A total of 531 patients were enrolled in the study, and the mean age was 78.75 days. The main etiologic agent causing bronchiolitis was RSV, accounting for 58.38% of infections. The total cost of bronchiolitis hospitalization was 2,958,786 euros. The mean cost per patient was significantly higher in the case of RSV (5,753.43 +/- 2,041.62 euros) compared to other etiology (5,395.15 +/- 2,040.87 euros) (p = 0.04). Discussion: The study confirms the high hospitalization cost associated with bronchiolitis. In detail, in the case of RSV etiology, the cost was higher compared to other etiology, which is likely due to the longer hospitalization and the more frequent admission to the intensive cure department. Conclusion: This study highlights that bronchiolitis is an important cost item even in a tertiary hospital and that cost-effective interventions targeting RSV are increasingly urgent

Epidemiology of fragility fractures in Italy

OBJECTIVES: We aimed to calculate the incidence of major fragility fractures in Italy, including those which do not result systematically in hospital admissions, on the basis of hospitalization rates provided in our previous researches.METHODS: We analyzed Italian national hospital discharge data from year 2004 to 2006 in order to determine age- and sex-specific incidence rates of hip, vertebral, humeral, and forearm fractures occurred in people aged 40 to 100 years of age. Re-hospitalizations of the same patients have been excluded from the analysis. Hospital discharge data have been adjusted taking into account recently published information concerning fracture-specific hospitalization rates.RESULTS: We estimated a total of 88,647 hip fractures in year 2006 among people aged 40 to 100 years old, with a +5.9% increase across the three examined years. Women aged >75 years old (n=53,259) accounted for 60% of total fractures observed both in males and females from 40 to 100 years of age. Concerning males, the highest incidence was observed between 80 and 84 years old (about 5,000 hip fractures). Overall incidence rate per 100,000 inhabitants computed for hip fractures was 284.28, with marked age- and sex-specific differences. Clinical vertebral fractures were estimated to be almost 61,000 in 2006, with a +3.1% increase across the three examined years. Overall incidence rate per 100,000 inhabitants computed for clinical vertebral fractures was 195.23, but this value doubled between 75 and 95 years of age. In the same year 2006, a total of 56,129 humeral and 97038 forearm/wrist fractures, with a +5.5% and +3.9% increase across three years, respectively. Overall humeral fractures incidence per 100,000 was 180, with highest rates (up to 600 and over) observed in women between 75 and 95 years of age, while incidence per 100,000 computed for wrist fractures was 311, with top values observed in women between aged 55-85 years old - thus including early post-menopausal age group - and a peak in those between 75 and 79 years of age.CONCLUSIONS: The burden of major osteoporotic fractures in Italy is very high. Preventive strategies aimed to reduce fractures incidence should be carried out at regional level

Updated incidence rates of fragility fractures in Italy: extension study 2002-2008

OBJECTIVES: We aimed to update the incidence rates of major fragility fractures in Italy, including those which do not result systematically in hospital admissions, on the basis of hospitalization rates provided in our previous researches.METHODS: We analyzed italian national hospital discharge data from year 2002 to 2008 in order to determine age- and sex-specific incidence rates of hip, vertebral, humeral, and forearm fractures occurred in people aged 40 to 100 years of age. Re-hospitalizations of the same patients have been excluded from the analysis. Hospital discharge data have been adjusted taking into account recently published information concerning fracture-specific hospitalization rates.RESULTS: We estimated a total of 91,494 hip fractures in year 2008 among people aged 40 to 100 years old, with a +18.1% increase across the seven-year period. Women aged >75 years old (n=55,950) accounted for about 60% of total fractures observed both in males and females. Concerning males, the highest incidence was observed between 80 and 84 years old (about 5,000 hip fractures). Overall incidence rate per 100,000 inhabitants computed for hip fractures was 283.5, with marked age- and sex-specific differences. Clinical vertebral fractures were estimated to be almost 61,000 in 2008, with a +6.3% increase over seven years. Overall incidence rate per 100,000 inhabitants computed for clinical vertebral fractures was 189.0, but this value doubled between 75 and 95 years of age. For the same year 2008, we estimated a total of 57,400 humeral and 94,000 forearm/wrist fractures, with a +13.2% and +0.7% increase over the seven-year period, respectively. Overall humeral fractures incidence per 100,000 was estimated in 178.0, with highest rates (up to 600 and over) observed in women between 75 and 95 years of age, while incidence per 100,000 for wrist fractures was computed in 298.0, with top values observed in women between aged 55 years old and over.CONCLUSION: The burden of major osteoporotic fractures in Italy is still increasing. Preventive strategies aimed to reduce fractures incidence should be carried out at regional level

Interaction of Pelargonium sidoides Compounds with Lactoferrin and SARS-CoV-2: Insights from Molecular Simulations

(1) Background: Pelargonium sidoides extracts and lactoferrin are two important natural, anti-inflammatory, and antiviral agents, which can interfere with the early stages of SARS-CoV-2 infection. Molecular docking and molecular dynamics simulation approaches have been applied to check for the occurrence of interactions of the Pelargonium sidoides compounds with lactoferrin and with SARS-CoV-2 components. (2) Methods: Computational methods have been applied to confirm the hypothesis of a direct interaction between PEL compounds and the lactoferrin protein and between Pelargonium sidoides compounds and SARS-CoV-2 Spike, 3CLPro, RdRp proteins, and membrane. Selected high-score complexes were structurally investigated through classical molecular dynamics simulation, while the interaction energies were evaluated using the molecular mechanics energies combined with generalized Born and surface area continuum solvation method. (3) Results: Computational analyses suggested that Pelargonium sidoides extracts can interact with lactoferrin without altering its structural and dynamical properties. Furthermore, Pelargonium sidoides compounds should have the ability to interfere with the Spike glycoprotein, the 3CLPro, and the lipid membrane, probably affecting the functional properties of the proteins inserted in the double layer. (4) Conclusion: Our findings suggest that Pelargonium sidoides may interfere with the mechanism of infection of SARS-CoV-2, especially in the early stages

N-Oleoyl-glycine reduces nicotine reward and withdrawal in mice.

Cigarette smokers with brain damage involving the insular cortex display cessation of tobacco smoking, suggesting that this region may contribute to nicotine addiction. In the present study, we speculated that molecules in the insular cortex that are sensitive to experimental traumatic brain injury (TBI) in mice might provide leads to ameliorate nicotine addiction. Using targeted lipidomics, we found that TBI elicited substantial increases of a largely uncharacterized lipid, N-acyl-glycine, N-oleoyl-glycine (OlGly), in the insular cortex of mice. We then evaluated whether intraperitoneal administration of OlGly would alter withdrawal responses in nicotine-dependent mice as well as the rewarding effects of nicotine, as assessed in the conditioned place preference paradigm (CPP). Systemic administration of OlGly reduced mecamylamine-precipitated withdrawal responses in nicotine-dependent mice and prevented nicotine CPP. However, OlGly did not affect morphine CPP, demonstrating a degree of selectivity. Our respective in vitro and in vivo observations that OlGly activated peroxisome proliferator-activated receptor alpha (PPAR-α) and the PPAR-α antagonist GW6471 prevented the OlGly-induced reduction of nicotine CPP in mice suggests that this lipid acts as a functional PPAR-α agonist to attenuate nicotine reward. These findings raise the possibility that the long chain fatty acid amide OlGly may possess efficacy in treating nicotine addiction