Split crest technique for implant treatment of agenesis of the upper lateral incisors: results of a randomized pilot histological and clinical study at 24-month follow-up

Agenesis of lateral incisors, besides the functional issues, represents a great esthetic drawback. The selection of an appropriate treatment is a complex decision, which should consider the stability of the clinical outcomes over time. The aim of the present study was a histological and clinical comparison of two-stage split crest technique (SCT), with bone chips alone or mixed with porcine bone in patients affected by unilateral and bilateral agenesis of the upper lateral incisors. Eleven patients were enrolled, and randomly assigned to receive a treatment with autologous bone chips (group 1) or autologous bone chips mixed 1:1 to porcine-derived xenogenic bone (group 2). After a 2-month healing period, implants were placed and biopsies harvested for histomorphometrical evaluation. Clinical assessment, according to ICOI PISA health scale, and radiographic marginal bone loss evaluation at 12- and 24-month follow-ups were conducted. The histomorphometry showed significantly greater new bone formation (p > 0.0229) in group 2. At 12- and 24-month follow-ups, all the evaluated implants, regardless of the group they were allocated, could be categorized as "success" in the ICOI Pisa Health Scale for Dental Implants, and did not show significant difference in crestal bone loss. To the best of our knowledge, these are the first histological and clinical outcomes indicating that the use of bone chips mixed 1:1 to porcine bone in SCT could be a promising technique for the rehabilitation of patients with agenesis of the upper lateral incisors, although studies with a larger number of patients and implants, and a longer follow up are needed

Uprighting impacted mandibular second molar using a skeletal anchorage: a case report

The aim of this case report is to present an innovative combined orthodontic-surgical technique to disimpact mandibular second molar (MM2) using an orthodontic miniscrew and an elastic chain. The impact on the Oral health-related quality of life (OHRQoL) was also evaluated. Using the present techinique, it is possible to expose the impacted tooth, insert a self-drilling miniscrew in the retromolar area, and remove the bud of third mandibular molar. At the same time the orthodontic force is applied with the use of an elastomeric chain that connects the head of miniscrew and vestibular and oral buttons bonded on MM2. A close traction is performed for the whole treatment time without the reactivation of the elastic force. The use of skeletal anchorage allowed the disimpaction of impacted MM2 in a short treatment time (about three months) avoiding the typical biomechanical side effects of traditional orthodontic appliance and increasing the effectiveness of the treatment. Further studies are necessary to evaluate the real advantages and disadvantages of this combined orthodontic-surgical approach

Short-range order and chemical compositions of glasses along the basaltic-rhyolite sub-alkaline join by Raman and FTIR spectroscopies

Six sub-alkaline glasses with compositions progressively shifting from the tholeiitic basalt (B100) end-member to the rhyolite (R100) end-member were investigated and analysed in the same frequency domain by both Raman and FTIR. This approach highlights spectroscopic similarities and differences such as positions, widths and intensities of Raman and FTIR bands, which may also exhibit significant overlapping. Both the Raman and FTIR spectra show several peaks grouped in three main vibrational windows: 200–650 (low frequency region, named F-I in this study), 650–850 (intermediate region, F-II) and 850–1250 cm−1 (high-frequency region, F-III). In line with previous investigations, the F-I interval can be ascribed to vibrational modes involving rings of tetrahedrally coordinated cations linked by bridging oxygens. It can be fitted with three components, whereas F-II involves the motion of Si atoms within its oxygen cage and is adequately represented by two components. Finally, F-III contains different T-O (T = tetrahedrally coordinated network-forming cation) stretching bands that can be tied to the overall degree of polymerization of the glass and are fitted with four components. In some glasses, the three and the two components within F-I and F-II are identifiable in both Raman and FTIR spectra; in cases of strong peak overlap, these peaks can be complementary to one another towards our interpretation of the molecular arrangement(s) in these glasses. Indeed, the positions of the four components in F-III are first constrained in the Raman spectra, which are more identifiable, then further refined using available Raman spectra for corresponding chemically simple silicate systems. The nine fitted components can reproduce the Raman and FTIR spectra extremely well. As a function of the amount of SiO2, the positions and intensities of the three low frequency components progressively shift in both Raman and FTIR. Similarly, the two bands in the F-II intermediate region exhibit a monotonic shifting of their positions. Indeed, the components at high frequency display less significant shifting of their positions as a function of SiO2, while their intensities change more markedly in the Raman spectrum compared to those for FTIR. The vibrational components measured in this study provide a referenced dataset of assignations of the most abundant natural volcanic glasses. Therefore, it provides a diagnostic tool based on the cross-validation of Raman and FTIR spectra to quickly identify the glass chemistry, offering the possibility to expand the applicability of remote investigations

Prospective phase II single-center study of the safety of a single very high dose of liposomal amphotericin B for antifungal prophylaxis in patients with acute myeloid leukemia.

Some preclinical and pharmacokinetic studies suggested the variable safety and the potential efficacy of an antifungal prophylaxis with a single high dose of liposomal amphotericin B (L-AmB) in high-risk patients. An open-label, prospective study was conducted with 48 adults receiving induction chemotherapy for acute myeloid leukemia (AML). Patients received a single infusion of 15 mg/kg of body weight L-AmB and, eventually, a second dose after 15 days of persistent neutropenia. The primary objective was tolerability and safety. Efficacy was also evaluated as a secondary endpoint. A pharmacokinetic study was performed with 34 patients in order to evaluate any association of plasma L-AmB levels with toxicity and efficacy. Overall, only 6 patients (12.5%) reported Common Toxicity Criteria (CTC) grade 3 hypokalemia, which was corrected with potassium supplementation in all cases, and no patient developed clinically relevant nephrotoxicity. Mild infusion-related adverse events occurred after 6 of 53 (11.3%) total infusions, with permanent drug discontinuation in only one case. Proven invasive fungal disease (IFD) was diagnosed in 4 (8.3%) patients. The mean AmB plasma levels at 6 h, 24 h, and 7 days after L-AmB administration were 160, 49.5, and 1 mg/liter, respectively. The plasma AmB levels were higher than the mean values of the overall population in 3 patients who developed CTC grade 3 hypokalemia and did not significantly differ from the mean values of the overall population in 3 patients who developed IFD. Our experience demonstrates the feasibility and safety of a single 15-mg/kg L-AmB dose as antifungal prophylaxis in AML patients undergoing induction chemotherapy

A human iPSC line capable of differentiating into functional macrophages expressing ZsGreen: a tool for the study and in vivo tracking of therapeutic cells

We describe the production of a human induced pluripotent stem cell (iPSC) line, SFCi55-ZsGr, that has been engineered to express the fluorescent reporter gene, ZsGreen, in a constitutive manner. The CAG-driven ZsGreen expression cassette was inserted into the AAVS1 locus and a high level of expression was observed in undifferentiated iPSCs and in cell lineages derived from all three germ layers including haematopoietic cells, hepatocytes and neurons. We demonstrate efficient production of terminally differentiated macrophages from the SFCi55-ZsGreen iPSC line and show that they are indistinguishable from those generated from their parental SFCi55 iPSC line in terms of gene expression, cell surface marker expression and phagocytic activity. The high level of ZsGreen expression had no effect on the ability of macrophages to be activated to an M(LPS + IFNγ), M(IL10) or M(IL4) phenotype nor on their plasticity, assessed by their ability to switch from one phenotype to another. Thus, targeting of the AAVS1 locus in iPSCs allows for the production of fully functional, fluorescently tagged human macrophages that can be used for in vivo tracking in disease models. The strategy also provides a platform for the introduction of factors that are predicted to modulate and/or stabilize macrophage function. This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’

Trends and Challenges in Experimental Macromolecular Crystallography

Macromolecular X-ray crystallography underpins the vigorous field of structural molecular biology having yielded many protein, nucleic acid and virus structures in fine detail. The understanding of the recognition by these macromolecules, as receptors, of their cognate ligands involves the detailed study of the structural chemistry of their molecular interactions. Also these structural details underpin the rational design of novel inhibitors in modern drug discovery in the pharmaceutical industry. Moreover, from such structures the functional details can be inferred, such as the biological chemistry of enzyme reactivity. There is then a vast number and range of types of biological macromolecules that potentially could be studied. The completion of the protein primary sequencing of the yeast genome, and the human genome sequencing project comprising some 105 proteins that is underway, raises expectations for equivalent three dimensional structural database

Systemic influences of mammary cancer on monocytes in mice

SIMPLE SUMMARY: Using a mouse model of breast cancer driven by the mammary epithelial expression of the polyoma middle T oncoprotein in which the tumors progress from benign to malignant metastatic stages, we show that cancer causes an increase in circulating monocytes and a splenomegaly. This increase in monocyte number is due to their increased proliferation in the bone marrow and not turnover rates in the blood. Single cell sequencing also shows that new populations of monocytes do not arise during cancer. Cancer also drives systemic changes in the monocyte transcriptome, with a notable down-regulation of interferon signaling. These systemic influences start in the bone marrow but intensify in the blood. Comparison of cancer prone and cancer resistant mouse inbred strains carrying the same oncogene reveals that the genetic background of the strain causes different monocyte transcriptional changes. Similarly, a comparison of the mouse transcriptome to human breast cancer monocyte profiles indicates limited similarities, to the extent that interferon signaling is enhanced in humans. Systemic responses are different in the same model of cancer on different genetic backgrounds within a species and even greater changes are found across species. These data suggest that at the very least this mouse model will be limited when it comes to exploring the mechanism behind systemic changes in humans. ABSTRACT: There is a growing body of evidence that cancer causes systemic changes. These influences are most evident in the bone marrow and the blood, particularly in the myeloid compartment. Here, we show that there is an increase in the number of bone marrow, circulating and splenic monocytes by using mouse models of breast cancer caused by the mammary epithelial expression of the polyoma middle T antigen. Cancer does not affect ratios of classical to non-classical populations of monocytes in the circulation nor does it affect their half-lives. Single cell RNA sequencing also indicates that cancer does not induce any new monocyte populations. Cancer does not change the monocytic progenitor number in the bone marrow, but the proliferation rate of monocytes is higher, thus providing an explanation for the expansion of the circulating numbers. Deep RNA sequencing of these monocytic populations reveals that cancer causes changes in the classical monocyte compartment, with changes evident in bone marrow monocytes and even more so in the blood, suggesting influences in both compartments, with the down-regulation of interferon type 1 signaling and antigen presentation being the most prominent of these. Consistent with this analysis, down-regulated genes are enriched with STAT1/STAT2 binding sites in their promoter, which are transcription factors required for type 1 interferon signaling. However, these transcriptome changes in mice did not replicate those found in patients with breast cancer. Consequently, this mouse model of breast cancer may be insufficient to study the systemic influences of human cancer

Deciphering myeloid-derived suppressor cells: isolation and markers in humans, mice and non-human primates

International audienceIn cancer, infection and inflammation, the immune system's function can be dysregulated. Instead of fighting disease, immune cells may increase pathology and suppress host-protective immune responses. Myeloid cells show high plasticity and adapt to changing conditions and pathological challenges. Despite their relevance in disease pathophysiology, the identity, heterogeneity and biology of myeloid cells is still poorly understood. We will focus on phenotypical and functional markers of one of the key myeloid regulatory subtypes, the myeloid derived suppressor cells (MDSC), in humans, mice and non-human primates. Technical issues regarding the isolation of the cells from tissues and blood, timing and sample handling of MDSC will be detailed. Localization of MDSC in a tissue context is of crucial importance and immunohistochemistry approaches for this purpose are discussed. A minimal antibody panel for MDSC research is provided as part of the Mye-EUNITER COST action. Strategies for the identification of additional markers applying state of the art technologies such as mass cytometry will be highlighted. Such marker sets can be used to study MDSC phenotypes across tissues, diseases as well as species and will be crucial to accelerate MDSC research in health and disease

Diagnosis and treatment of a rare case of adenomatoid odontogenic tumor in a young patient affected by attenuated familial adenomatosis polyposis (aFAP): case report and 5 year follow-up

Abstract. -BACKGROUND: The adenomatoid odontogenic tumor (AOT) is a quite rare odontogenic tumor, with an incidence rate of approximately 12 cases/year worldwide. Attenuated familial adenomatous polyposis (aFAP) is a syndrome characterized by a significant risk to develop colon cancer. The aim of the paper is to describe a case never reported before in the literature: an AOT developed in a patient with aFAP; moreover, we want to show how it appears 5 years after surgery and after the regeneration of the eroded bone tissue, using the PlateletRich Fibrin (PRF) as filling material. CASE PRESENTATION: We report the case of a female 18 years old patient, affected by aFAP; she comes to us with a swelling on the right hemi-face. We performed several radiological exams, and they showed a neoformation approximately 2 cm in diameter: this neoformation packed the upper right canine, therefore, we hypothesized a dentigerous cyst. We decided to proceed to open biopsy and enucleation of the lesion. An intra-operative endodontic treatment on the adjacent partially resorbed teeth was also performed. Finally, we performed a reconstruction of eroded bone tissue, by use of Platelet-Rich Fibrin as filling material. The samples fixed and embedded in paraffin have led to the diagnosis of AOT. After 5 years from the surgery, we did not find any clear sign of relapse, in addition, the use of PRF has favored an optimal osteogenesis at the surgical site. The onset of an AOT is quite rare in the general population, and this rarity could represent a critical point for its diagnosis; AOT onset in a patient with aFAP is a finding that could represent a new element of diagnosis and, therefore, the starting point to perform a more effective therapy