The reduction of intracellular 1,4,5-inositol trisphosphate (IP 3 ) levels stimulates autophagy, whereas the enhancement of IP 3 levels inhibits autophagy induced by nutrient depletion. Here, we show that knockdown of the IP 3 receptor (IP 3 R) with small interfering RNAs and pharmacological IP 3 R blockade is a strong stimulus for the induction of autophagy. The IP 3 R is known to reside in the membranes of the endoplasmic reticulum (ER) as well as within ER-mitochondrial contact sites, and IP 3 R blockade triggered the autophagy of both ER and mitochondria, as exactly observed in starvation-induced autophagy. ER stressors such as tunicamycin and thapsigargin also induced autophagy of ER and, to less extent, of mitochondria. Autophagy triggered by starvation or IP 3 R blockade was inhibited by Bcl-2 and Bcl-X L specifically targeted to ER but not Bcl-2 or Bcl-X L proteins targeted to mitochondria. In contrast, ER stress-induced autophagy was not inhibited by Bcl-2 and Bcl-X L . Autophagy promoted by IP 3 R inhibition could not be attributed to a modulation of steady-state Ca 2 þ levels in the ER or in the cytosol, yet involved the obligate contribution of Beclin-1, autophagy-related gene (Atg)5, Atg10, Atg12 and hVps34. Altogether, these results strongly suggest that IP 3 R exerts a major role in the physiological control of autophagy. The first step of macroautophagy consists in the gradual envelopment of cytoplasmic material (cytosol and/or organelles) in the phagophore, a cistern that finally sequesters cytoplasmic material in autophagosomes (also called autophagic vacuoles (AVs)) lined by two membranes. Autophagosomes then undergo a progressive maturation by fusion with endosomes and/or lysosomes. This latter step creates autolysosomes in which the inner membrane as well as the luminal content of the AVs is degraded by lysosomal enzymes. The process of autophagy is controlled by a series of evolutionary conserved genes, the atg genes, whose products are essential for specific steps of the autophagic process. 1,2One of the strongest triggers of autophagy is nutrient stress. 3,4 In response to starvation, cells degrade nonessential components thereby generating nutrients for meeting the cell's energetic demand as well as for vital biosynthetic reactions. In such circumstances, when autophagy is an adaptation, inhibition of autophagy has a negative impact on cell survival. For example, mice lacking the atg5 gene survive without any major developmental defect until birth, yet succumb to the stressful neonatal period unless puppies are force-fed with milk within the first hours after birth.5 Similarly, human cell lines cultured in nutrient-free media mount a cytoprotective autophagic response. Suppression of autophagy by chemical inhibitors or knockdown of essential genes thus sensitize cells to starvation-induced cell death. 6,7Autophagy inhibition also sensitizes cells to the depletion of obligatory growth (or survival) factors resulting in a decrease of nutrient import through the plasma membrane. For example...

Introduction. Maxillary sinus surgery is a reliable and predictable treatment option for the prosthetic rehabilitation of the atrophic maxilla. Nevertheless, these interventions are not riskless of postoperative complications with respect to implant positioning in pristine bone. Aim. The aim of this paper is to report the results of a clinical consensus of experts (periodontists, implantologists, maxillofacial surgeons, ENT, and microbiology specialists) on several clinical questions and to give clinical recommendations on how to prevent, diagnose, and treat postoperative infections. Materials and Methods. A panel of experts in different fields of dentistry and medicine, after having reviewed the available literature on the topic and taking into account their long-standing clinical experience, gave their response to a series of clinical questions and reached a consensus. Results and Conclusion. The incidence of postop infections is relatively low (2%–5.6%). A multidisciplinary approach is advisable. A list of clinical recommendation are given.

Abstract. This chapter presents a number of illustrative case studies of a wide range of applications of multiobjective optimization methods, in areas ranging from engineering design to medical treatments. The methods used include both conventional mathematical programming and evolutionary optimization, and in one case an integration of the two approaches. Although not a comprehensive review, the case studies provide evidence of the extent of the potential for using classical and modern multiobjective optimization in practice, and opens many opportunities for further research. IntroductionThe intention with this chapter is to provide illustrations of real applications of multiobjective optimization, covering both conventional mathematical programming approaches and evolutionary multiobjective optimization. These illustrations do cover a broad range of application, but do not attempt to provide a comprehensive review of applications.

Immediate loading of root-form dental implants has shown promising results and offers treatment cost and convenience advantages to patients. Although blade implants have been immediately loaded for over 2 decades, the ability of this implant design to achieve osseointegration has been debated. The aim of the present study was to histologically evaluate the peri-implant tissues of an immediately loaded blade implant retrieved for abutment fracture after a 20-year loading period. Histologic samples were prepared and examined by light microscope. Compact, cortical, mature bone with well-formed osteons was present at the interface of the implant. Bone-to-implant contact was 51% +/- 6%. The histologic data showed that osseointegration was obtained in an immediately loaded blade implant inserted into the mandible, and that mineralized tissues were maintained at the interface over a long period (20 years).

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