Parameters for the mathematical modelling of Clostridium difficile acquisition and transmission: a systematic review

INTRODUCTION: Mathematical modelling of Clostridium difficile infection dynamics could contribute to the optimisation of strategies for its prevention and control. The objective of this systematic review was to summarise the available literature specifically identifying the quantitative parameters required for a compartmental mathematical model of Clostridium difficile transmission. METHODS: Six electronic healthcare databases were searched and all screening, data extraction and study quality assessments were undertaken in duplicate. Results were synthesised using a narrative approach. RESULTS: Fifty-four studies met the inclusion criteria. Reproduction numbers for hospital based epidemics were described in two studies with a range from 0.55 to 7. Two studies provided consistent data on incubation periods. For 62% of cases, symptoms occurred in less than 4 weeks (3-28 days) after infection. Evidence on contact patterns was identified in four studies but with limited data reported for populating a mathematical model. Two studies, including one without clinically apparent donor-recipient pairs, provided information on serial intervals for household or ward contacts, showing transmission intervals of <1 week in ward based contacts compared to up to 2 months for household contacts. Eight studies reported recovery rates of between 75%-100% for patients who had been treated with either metronidazole or vancomycin. Forty-nine studies gave recurrence rates of between 3% and 49% but were limited by varying definitions of recurrence. No study was found which specifically reported force of infection or net reproduction numbers. CONCLUSIONS: There is currently scant literature overtly citing estimates of the parameters required to inform the quantitative modelling of Clostridium difficile transmission. Further high quality studies to investigate transmission parameters are required, including through review of published epidemiological studies where these quantitative estimates may not have been explicitly estimated, but that nonetheless contain the relevant data to allow their calculation

Choroid plexus trafficking of immune cells towards the rat cochlear nuclei after noise trauma or cochlear destruction

Cochlear nuclei are the first CNS station of auditory pathways, and the sole target of primary auditory fibers from the cochlea, which terminate in a frequency-dependent (tonotopic) pattern. Cochlear nuclei include a ventral nucleus (VCN) involved in binaural comparisons and a dorsal nucleus (DCN) involved in the integration of auditory and nonauditory stimuli. Circuital responses to peripheral damage, such as noise trauma or cochlear destruction, are quite different between VCN and DCN, possibly related to different auditory pathologies (e.g. tinnitus and speech comprehension deficit in noise vs errors in sound localization in space). Microglial responses would be therefore expected to also display differences. However, most studies have so far concentrated on the VCN. We investigated the changes of DCN-related Iba1+ cells after 10 kHz noise trauma and unilateral cochlear destruction. A week after cochlear destruction, disorganized clusters of Iba1+ cells appeared at the ipsilateral DCN surface facing the 4th ventricle, especially at contact sites with the choroid plexus and cerebellum, whereas a rod microglia train was observed at the surface of the contralateral DCN. An increase in ring-shaped and dystrophic microglia was also observed in the ipsilateral DCN. In the choroid plexus, moreover, Iba1+ cells were significantly more numerous on both sides. Three days after noise trauma, Iba1+ cells increased in density and displayed activated morphology in the DCN region corresponding to noise trauma frequencies. At 12 days after trauma, activation had spread through the whole DCN, and superficial clusters of Iba1+ cells and choroid plexus Iba1+ cell increase was observed as for cochlear destruction. Morphological shifts were also observed in the microglial population, with an increase of ring-shaped and amoeboid (but not dystrophic) microglia. Minocycline bolished changes in Iba1+ cell density due to damage, although not morphological activation signs; stereotaxic (LPS) injections in the DCN induced instead a strong local amoeboid microgliosis. On the other hand, neither treatment affected choroid plexus macrophage density. These data suggest that the response of the Iba1+ population after peripheral trauma includes contribution from both local microglia and choroid plexus-derived factors. In order to differentiate Iba1+ populations and assess their relative importance, we labeled them selectively for CCR2 (for inflowing macrophages) and Tmem119 (for resident microglia). Moreover, we labeled other cell types (mast cells, neutrophils) at early stages after damage, counting them in choroid plexus and DCN parenchyma. The present work suggests that the DCN, in addition to integrating nonauditory context nerve signals with auditory stimuli, also integrates immune factors crossing its ventricular surface, possibly in order to differentiate physiological and pathological stimulation patterns

Assisted evaluation of antibiotic resistance development in Pseudomonas aeruginosa from intensive care units.

421 strains of Pseudomonas aeruginosa were isolated from patients admitted to intensive care units and tested with automated systems for sensitivity to 21 antimicrobial agents. Data were collected in a database for evaluation and monitoring of resistance development. Results showed that assisted monitoring of antimicrobial resistance gives continuously updated information, with particular attention to the different local therapeutical schedules. It is therefore advisable that clinicians constantly exchange information with the microbiology laboratory through a hospital information system in which data from different laboratories are pooled in real time

Photoinduction of micronuclei by 4,4',6 trimethylangelicin and 8-methoxypsoralen in different experimental models

The frequencies of micronuclei induced by treatment with 4,4',6-trimethylangelicin (TMA) and 8-methoxypsoralen (8-MOP) have been compared in the following experimental models: (1) peripheral normochromatic erythrocytes (NCE) during 10 days after single p.o. administration of TMA or 8-MOP in male and female mice; (2) peripheral NCE during photocarcinogenesis by TMA or 8-MOP topically administered to female mice; (3) primary cultures of human skin fibroblasts treated with TMA or 8-MOP. The frequency of micronuclei in peripheral NCE of mice (both sexes) was significantly enhanced after p.o. administration of TMA or 8-MOP. This latter was more active than TMA in inducing chromosomal damage. No increased frequencies of micronuclei in peripheral NCE were detected in mice subjected to TMA or 8-MOP photocarcinogenic treatment, even when malignancies developed. In human fibroblast cultures, at equimolar concentrations, the induction of lethal effects by TMA in the presence of 365-nm radiation was higher than that exerted by 8-MOP. At equal survival, however, TMA showed practically the same activity as 8-MOP in the induction of micronuclei. Our findings provide evidence of genotoxicity by TMA administered p.o. without irradiation and give further information about photogenotoxicity of these substances

DANNO AL DNA IN CELLULE DELL’IPPOCAMPO DI GERBILLO DOPO TRATTAMENTO DI ISCHEMIA/RIPERFUSIONE

La riperfusione post-ischemica rappresenta una significativa causa di morbilità e di morte in diversi campi della medicina che comprendono, tra gli altri, l'infarto del miocardio, l'ischemia cerebrale, lo shock settico o emorragico e il trapianto d'organo. A livello del microcircolo il danno da ischemia/riperfusione (I/R) è provocato, oltre che dall'accumulo chemiotattico e dall'adesione all'endotelio di leucociti circolanti, dalla generazione di specie reattive dell'ossigeno e dell'azoto quali l'anione superossido e il perossinitrito. Il danno al DNA da parte di queste specie reattive è stato dimostrato sia in modelli sperimentali in vitro che in cellule in cultura. Una procedura sperimentale efficace per mettere in evidenza il danno al DNA sotto forma di rotture a singola elica (SSB) in cellule in cultura è la micro-gel-elettroforesi su singola cellula (Comet test). Una modifica di questa tecnica (Halo-Diffusion Assay - HDA) consente di evidenziare anche la frammentazione cromatinica, strettamente correlata all’apoptosi. Recentemente, l’esecuzione di questi saggi si è resa possibile usando come campione anche frammenti tissutali provenienti da animali da esperimento

The effect of selective low-density lipoprotein apheresis on plasma lipoperoxides and antioxidant vitamins in familial hypercholesterolemic patients

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterized by a lifelong elevation in the concentration of low-density lipoprotein (LDL) bound cholesterol in blood by cholesterol deposits and by early coronary artery disease. The LDL apheresis technique has been introduced with the goal of reducing LDL cholesterol levels, thereby preventing the development of atherosclerosis. The literature on LDL apheresis reports 2 different facets, the therapeutic aspect associated with the lessening of LDL concentration and the initiation of a peroxidation process associated with the biocompatibility of the artificial membrane. Lipid and protein peroxidation gives rise to toxic and atherogenic hydroperoxide, mostly lipid hydroperoxides, and derivative compounds, which may offset the benefit of the procedure. In this paper, plasma hydroperoxide levels are determined along with the elevation of the serum and LDL antioxidant status in hypercholesterolemic patients before and following repeated LDL apheresis sessions. Hydroperoxide concentration has been expressed both in terms of plasma volume and LDL concentration. A highly significant increase in LDL lipid hydroperoxides is demonstrated when expressed in terms of LDL concentration and is associated with the LDL apheresis procedure. The usefulness of antioxidant supplementation in LDL apheresis is discussed

Use of serum markers in the diagnosis and management of laryngeal cancer

Many neoplastic diseases are reported to be accompanied by the presence or associated with an increase in biological substances identified as tumour markers. The most common markers implicated in head and neck cancers are CEA, TPA, LASA, SCC, CA 19-9, and ferritin. These markers (except SCC) were evaluated in 50 patients with a laryngeal carcinoma, in 20 patients with benign lesions, and in 20 healthy subjects. The results show for each marker assayed the following sensitivity values (true positives): CEA, 10%; CA 19-9, 30%; TPA, 30%; LASA, 90%; ferritin, 60%. Specificity (true negatives) was as follows: CEA, 85%; CA 19-9, 99.4%; TPA, 98%; LASA, 99.8%; ferritin, 97%. LASA and ferritin seem to be the most suitable markers for patient monitoring because of their higher sensitivity in all phases of cancer disease