Do Neutrophils Play a Role in Establishing Liver Abscesses and Distant Metastases Caused by Klebsiella pneumoniae?

Serotype K1 Klebsiella pneumoniae is a major cause of liver abscesses and endophthalmitis. This study was designed to identify the role of neutrophils in the development of distant metastatic complications that were caused by serotype K1 K. pneumoniae. An in vitro cellular model was used to assess serum resistance and neutrophil-mediated killing. BALB/c mice were injected with neutrophils containing phagocytosed K. pneumoniae. Serotype K1 K. pneumoniae was significantly more resistant to serum killing, neutrophil-mediated phagocytosis and intra-cellular killing than non-K1 isolates (p<0.01). Electron microscopic examination had similar findings as in the bioassay findings. Intraperitoneal injection of neutrophils containing phagocytosed serotype K1 K. pneumoniae led to abscess formation in multiple sites including the subcutaneous tissue, lung, and liver, whereas no abscess formation was observed in mice injected with non-K1 isolates. The resistance of serotype K1 K. pneumoniae to complement- and neutrophil-mediated intracellular killing results in the dissemination of K. pneumoniae via the bloodstream. Escape from neutrophil intracellular killing may contribute to the dissemination and establishment of distant metastases. Thus, neutrophils play a role as a vehicle for helping K. pneumoniae and contributing to the establishment of liver abscess and distant metastatic complications

Modeling the Effects of Cell Cycle M-phase Transcriptional Inhibition on Circadian Oscillation

Circadian clocks are endogenous time-keeping systems that temporally organize biological processes. Gating of cell cycle events by a circadian clock is a universal observation that is currently considered a mechanism serving to protect DNA from diurnal exposure to ultraviolet radiation or other mutagens. In this study, we put forward another possibility: that such gating helps to insulate the circadian clock from perturbations induced by transcriptional inhibition during the M phase of the cell cycle. We introduced a periodic pulse of transcriptional inhibition into a previously published mammalian circadian model and simulated the behavior of the modified model under both constant darkness and light–dark cycle conditions. The simulation results under constant darkness indicated that periodic transcriptional inhibition could entrain/lock the circadian clock just as a light–dark cycle does. At equilibrium states, a transcriptional inhibition pulse of certain periods was always locked close to certain circadian phases where inhibition on Per and Bmal1 mRNA synthesis was most balanced. In a light–dark cycle condition, inhibitions imposed at different parts of a circadian period induced different degrees of perturbation to the circadian clock. When imposed at the middle- or late-night phase, the transcriptional inhibition cycle induced the least perturbations to the circadian clock. The late-night time window of least perturbation overlapped with the experimentally observed time window, where mitosis is most frequent. This supports our hypothesis that the circadian clock gates the cell cycle M phase to certain circadian phases to minimize perturbations induced by the latter. This study reveals the hidden effects of the cell division cycle on the circadian clock and, together with the current picture of genome stability maintenance by circadian gating of cell cycle, provides a more comprehensive understanding of the phenomenon of circading gating of cell cycle

Video-assisted minimally invasive parathyroidectomy: benefits and long-term results

Abstract BACKGROUND: In recent years several endoscopic and video-assisted techniques for parathyroidectomy have been described. The role of these techniques, with respect to time-honored conventional surgery, has been largely debated. This paper was designed to review the evidence, and make the recommendations, for the video-assisted/endoscopic approach to parathyroidectomy. METHODS: A database search was conducted in PubMed from which abstracts were screened matching our definition. Publications were further assessed and assigned their respective level of evidence. Additional data were obtained on the basis of our personal experience. RESULTS: Thirty-eight mainly retrospective studies have been published. Only four small, prospective, randomized trials, providing level II evidence, and one retrospective case-control comparative study, providing level IV evidence, have been found. Minimally invasive video-assisted parathyroidectomy (MIVAP) has emerged as one of the leading techniques. To date several randomized studies have shown that MIVAP is an efficacious and feasible procedure with the same complications rate as conventional surgery. Moreover, MIVAP seems to have significant advantages in terms of cosmetic result, postoperative pain and recovery, and patient satisfaction. CONCLUSIONS: From an evidence-based point of view, MIVAP should be considered a valid and validated option for the treatment of sporadic primary hyperparathyroidism sustained by a well-localized, single adenoma. Its role for the treatment of multiglandular diseases (familial hyperparathyroidism, secondary hyperparathyroidism) needs to be better clarified