Mathematical modelling in risk/exposure assessment of tobacco related lung cancer

The existence of a dose-related increase of lung cancer riskin cigarette smokers has been indisputably established. Thisfinding, however, is not confirmed at low doses (< 5 cigarettes/day),there still being a lack of epidemiological data. The use ofmathematical models of carcinogenesis to extrapolate from higherdoses allows estimation of the risk for very light smokers.The present study has been designed to compare a set of mathematicalmodels, i.e. one-hit, two-stage, multi-stage, logit, probit,and Weibull, in extrapolating relative risks at low doses fromthe data of nine large cohort studies on cigarette smokers reportedin the IARC Scientific Monograph on tobacco smoking. All modelsevaluated, apart from the one-hit, achieved a good fit, withthe proportion of explained variance ranging between 61% and67%. The relative risk estimates for passive smokers from themost updated epidemiological studies were taken into accountto evaluate, on the basis of these models, the correspondingexposure in terms of ‘cigarette equivalent’ smoked.These values ranged from 0.21 to 0.43 cigarettes/day for thetwo-stage and multistage model, while probit, logit and Weibullmodels, yielded estimates one or even two orders of magnitudelower. The authors emphasize the substantial agreement betweenthe estimates of ‘cigarette equivalent9 based on the applicationof two-stage and multi-stage models to the epidemiological evidenceon the effect of passive smoking and to the data based on thecomparison of tobacco metabolites in active and passive smokers.     

In Vitro and In Vivo Antimicrobial Activities of Gallium Nitrate against Multidrug-Resistant Acinetobacter baumannii

Multidrug-resistant Acinetobacter baumannii poses a tremendous challenge to traditional antibiotic therapy. Due to the crucial role of iron in bacterial physiology and pathogenicity, we investigated iron metabolism as a possible target for anti-A. baumannii chemotherapy using gallium as an iron mimetic. Due to chemical similarity, gallium competes with iron for binding to several redox enzymes, thereby interfering with a number of essential biological reactions. We found that Ga(NO₃)₃, the active component of an FDA-approved drug (Ganite), inhibits the growth of a collection of 58 A. baumannii strains in both chemically defined medium and human serum, at concentrations ranging from 2 to 80 μM and from 4 to 64 μM, respectively. Ga(NO₃)₃ delayed the entry of A. baumannii into the exponential phase and drastically reduced bacterial growth rates. Ga(NO₃)₃ activity was strongly dependent on iron availability in the culture medium, though the mechanism of growth inhibition was independent of dysregulation of gene expression controlled by the ferric uptake regulator Fur. Ga(NO₃)₃ also protected Galleria mellonella larvae from lethal A. baumannii infection, with survival rates of ≥75%. At therapeutic concentrations for humans (28 μM plasma levels), Ga(NO₃)₃ inhibited the growth in human serum of 76% of the multidrug-resistant A. baumannii isolates tested by ≥90%, raising expectations on the therapeutic potential of gallium for the treatment of A. baumannii bloodstream infections. Ga(NO₃)₃ also showed strong synergism with colistin, suggesting that a colistin-gallium combination holds promise as a last-resort therapy for infections caused by pan-resistant A. baumannii.     

Glomerular filtration rate in the elderly and in the oldest old: correlation with frailty and mortality

The equations for estimating kidney function have become very popular in the last decade. However, the clinical and prognostic meaning of these measures may be very different in older populations. Two cohorts of people aged 65–89 years (older sample) and 90 or more (oldest old sample) were used to investigate the prognostic significance of estimated glomerular filtration rate (eGFR). Additionally, we also investigated whether combining frailty and eGFR may improve the accuracy of frailty in predicting mortality. We found that lower eGFR values were significantly more frequent among frail subjects in both groups. eGFR < 30 was associated with increased risk for all-cause mortality either in subjects aged 65–89 years (HR = 3.71, 95% CI = 1.23–11.2) or in those aged 90 or more (HR = 1.53, 95% CI = 1.05–2.23). In the latter group, a not significant trend for increasing mortality was also observed among people with eGFR > 60 (HR = 1.28, 95% CI = 0.72–2.26). In addition, the oldest old subjects with eGFR > 60 and eGFR < 30 had the lowest hand-grip strength and ADL values. Combining eGFR and frailty status significantly improved the accuracy of frailty in predicting mortality only in the older sample. In conclusion, a U-shaped relationship exists between eGFR and mortality in the oldest old, but not in older individuals. Our findings suggest that eGFR needs to be adjusted for muscle mass/physical performance when estimating kidney function in people aged 90 or more. Nevertheless, in subjects aged 65–89 years, eGFR may improve the accuracy of frailty status in predicting prognosis, thus suggesting that eGFR may represent an additional dimension of frailty syndrome.     

Electrochemical and optoelectronic properties of terthiophene- and bithiophene-based polybenzofulvene derivatives

The electrochemical behavior of some polybenzofulvene derivatives bearing bithiophene (BT) or terthiophene (TT) side chains was investigated by cyclic voltammetry. Very interestingly, the presence of unsubstituted terminal thiophene moieties allowed poly-6-BT-BF3k and poly-6-TT-BF3k to be cross-linked by electrochemical procedures. Conductive films were obtained by electrodeposition from solutions of these polymers onto electrode surfaces through the formation of covalent cross-linking due to dimerization (i.e. electrochemical oxidation) of the BT or TT side chains. The films showed electrochromic features and switched from yellow-orange (neutral) to green (positively charged) by switching the potential, and were stable to tenths of cycles, without degradation in the wet state in the electrolyte solution. Finally, the thin film obtained by electrodeposition of poly-6-TT-BF3k on a indium tin oxide (ITO) glass substrate showed in the neutral state a significantly red-shifted photoluminescence (PL) emission (∼40 nm red-shifted with respect to that of the corresponding film obtained by casting procedures), which was consistent with the presence of more conjugated moieties produced by the oxidative dimerization of the TT side chains. The innovative architecture and the easy preparation could lead to a broad range of applications in optoelectronics and bioelectronics for these cross-linked hybrid materials based on π-stacked polybenzofulvene backbones bearing oligothiophene side chains.

The electrochemical behavior of some polybenzofulvene derivatives bearing bithiophene (BT) or terthiophene (TT) side chains was investigated by cyclic voltammetry and cross-linked materials were obtained by dimerization of the BT or TT side chains.     

Influence of a metaphylactic treatment with Baycox® Bovis on the reproductive performances of Fresian heifers: a preliminary study

A blind, randomised, controlled, multicentric field trial was conducted to assess the influence of a metaphylactic treatment with an oral solution of toltrazuril on some reproductive parameters of Italian Fresian heifers during the first 18–20 months of life. For this goal 40 calves were selected from two dairy farms and randomly divided into two homogeneous groups: MTol, treated with toltrazuril and NegC, left untreated. The calves were clinically and coprologically examined over the entire study period. The body condition scores, the body weights and the age at the first service were recorded and compared between the two groups, in addition to some other reproductive parameters including number of pregnancies, average service per pregnancy, conception rate, conception rate at first service and post first service conception rate. The analysis of the results showed that the metaphylactic treatment with toltrazuril influenced positively the average age of the first service (MTol 461.4 days versus NegC 485.45 days), the overall conception rate (MTol 95 % versus NegC 85 %), the success at first (MTol 60 % versus NegC 45 %) and second (MTol 75 % versus NegC 45 %) services and, consequently, the mean number of services to be carried out for each animal (MTol 1.4?±?0.6 versus NegC 1.6?±?0.79). Furthermore, the results confirmed that toltrazuril treatment, applied in accordance with the epidemiological aspects of each farm, is highly efficacious in persistent reduction of oocyst excretions with particular reference to Eimeria zuernii, Eimeria bovis, considered to be mainly responsible for clinical coccidiosis.     

Short interval intracortical facilitation correlates with the degree of disability in multiple sclerosis

BackgroundThe Expanded Disability Status Scale (EDSS) is the most widely used measure of disability in MS, however because of its limitations surrogate markers of clinical disability progression are of high interest. Transcranial magnetic stimulation (TMS) measures of demyelination and cortical excitability correlate with disability levels in MS.ObjectiveAim of this study was testing whether paired pulse (pp) TMS represents a reliable surrogate marker to measure clinical disability in MS.MethodsppTMS measures of intracortical synaptic transmission such as short interval intracortical inhibition (SICI), long interval intracortical inhibition (LICI), short interval intracortical facilitation (SICF) and intracortical facilitation (ICF) were collected from 74 patients affected by MS. Correlation of EDSS scores with ppTMS measures was analyzed.ResultsEDSS scores correlated with patient’s age, disease duration, Motor Evoked Potentials latency and thresholds and SICF measures but not with age of onset, SICI, ICF and LICI.ConclusionsThese findings support a possible use of SICF and MEP latency as surrogate markers of disability in MS. Further research is warranted to determine the role of SICF in the follow up of disease progression and to validate its use as an endpoint in multiple sclerosis clinical trials.