Iron and Sphingolipids as Common Players of (Mal)Adaptation to Hypoxia in Pulmonary Diseases

Hypoxia, or lack of oxygen, can occur in both physiological (high altitude) and pathological conditions (respiratory diseases). In this narrative review, we introduce high altitude pulmonary edema (HAPE), acute respiratory distress syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD), and Cystic Fibrosis (CF) as examples of maladaptation to hypoxia, and highlight some of the potential mechanisms influencing the prognosis of the affected patients. Among the specific pathways modulated in response to hypoxia, iron metabolism has been widely explored in recent years. Recent evidence emphasizes hepcidin as highly involved in the compensatory response to hypoxia in healthy subjects. A less investigated field in the adaptation to hypoxia is the sphingolipid (SPL) metabolism, especially through Ceramide and sphingosine 1 phosphate. Both individually and in concert, iron and SPL are active players of the (mal)adaptation to physiological hypoxia, which can result in the pathological HAPE. Our aim is to identify some pathways and/or markers involved in the physiological adaptation to low atmospheric pressures (high altitudes) that could be involved in pathological adaptation to hypoxia as it occurs in pulmonary inflammatory diseases. Hepcidin, Cer, S1P, and their interplay in hypoxia are raising growing interest both as prognostic factors and therapeutical targets

Challenges in Dental Statistics: Survey Methodology Topics

This paper gathers some contributions concerning survey methodology in dental research, as discussed during the first Workshop of the SISMEC STATDENT working group on statistical methods and applications in dentistry, held in Ancona on the 28th September 2011. The first contribution deals with the European Global Oral Health Indicators Development (EGOHID) Project which proposed a comprehensive and standardized system of epidemiological tools (questionnaires and clinical forms) for national data collection on oral health in Europe. The second contribution regards the design and conduct of trials to evaluate the clinical efficacy and safety of toothbrushes and mouthrinses. Finally, a flexible and effective tool used to trace dental age reference charts tailored to Italian children was presented

Challenges in Dental Statistics: Survey Methodology Topics

This paper gathers some contributions concerning survey methodology in dental research, as discussed during the first Workshop of the SISMEC STATDENT working group on statistical methods and applications in dentistry, held in Ancona on the 28th September 2011. The first contribution deals with the European Global Oral Health Indicators Development (EGOHID) Project which proposed a comprehensive and standardized system of epidemiological tools (questionnaires and clinical forms) for national data collection on oral health in Europe. The second contribution regards the design and conduct of trials to evaluate the clinical efficacy and safety of toothbrushes and mouthrinses. Finally, a flexible and effective tool used to trace dental age reference charts tailored to Italian children was presented

The physics models of FLUKA: status and recent development

A description of the intermediate and high energy hadronic interaction models used in the FLUKA code is given. Benchmarking against experimental data is also reported in order to validate the model performances. Finally the most recent developments and perspectives for nucleus-nucleus interactions are described together with some comparisons with experimental data.Comment: talk from the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla, Ca, USA, March 2003, 10 pages, p

Oxidative Stress Markers to Investigate the Effects of Hyperoxia in Anesthesia

Oxygen (O-2) is commonly used in clinical practice to prevent or treat hypoxia, but if used in excess (hyperoxia), it may act as toxic. O-2 toxicity arises from the enhanced formation of Reactive Oxygen Species (ROS) that exceed the antioxidant defenses and generate oxidative stress. In this study, we aimed at assessing whether an elevated fraction of inspired oxygen (FiO(2)) during and after general anesthesia may contribute to the unbalancing of the pro-oxidant/antioxidant equilibrium. We measured five oxidative stress biomarkers in blood samples from patients undergoing elective abdominal surgery, randomly assigned to FiO(2) = 0.40 vs. 0.80: hydroperoxides, antioxidants, nitrates and nitrites (NOx), malondialdehyde (MDA), and glutathionyl hemoglobin (HbSSG). The MDA concentration was significantly higher 24 h after surgery, and the body antioxidant defense lower, in the FiO(2) = 0.80 group with respect to both the FiO(2) = 0.40 group and the baseline values (p <= 0.05, Student's t-test). HbSSG in red blood cells was also higher in the FiO(2) = 0.80 group at the end of the surgery. NOx was higher in the FiO(2) = 0.80 group than the FiO(2) = 0.40 group at t = 2 h after surgery. MDA, the main end product of the peroxidation of polyunsaturated fatty acids directly influenced by FiO(2), may represent the best marker to assess the pro-oxidant/antioxidant equilibrium after surgery

The Influence of Dental Occlusion on Spectrophotometric Tooth Color Determinations

Background: Shade matching is a significant treatment step and a challenge for the clinical team with potentially high costs for color correction. Currently, in the United States, the majority of private dental practitioners use visual color matching, but a recent study has reported a high rate of mistakes of subjective color determination among graduate dentists. Objective: The aim of this retrospective study is to analyze whether a change in the oral background due to dental occlusion can influence tooth color determination. Methods: Volunteer dental students underwent spectrophotometric color assessment using the SpectroShade device. Two measurements were carried out (with the individuals’ occlusion closed and with the occlusion open) on 43 upper central and 58 lateral incisors. Association between colorimetric variables L*, a*, b* and ΔE00 and tooth width, length and tobacco usage were examined. Results: Slight changes in the CIELAB values between closed and open occlusions were found for both the gingival and the central sections as for the overall tooth area, with mean ΔL*=-1.24, Δa*=-1.77, Δb*=-1.42 and ΔE00=1,84. A larger difference was detected in the incisal area, with mean ΔL*=-2.99, Δa*=-1.76, Δb*=-2.83 and ΔE00=3.65. Conclusion: In conclusion, our study showed that dental occlusion does not play a significant role in tooth color matching determinations, even though attention to avoid overbite due to a maximum intercuspation should be made

The influence of dental occlusion on spectrophotometric tooth color determinations

Background: Shade matching is a significant treatment step and a challenge for the clinical team with potentially high costs for color correction. Currently, in the United States, the majority of private dental practitioners use visual color matching, but a recent study has reported a high rate of mistakes of subjective color determination among graduate dentists. Objective: The aim of this retrospective study is to analyze whether a change in the oral background due to dental occlusion can influence tooth color determination. Methods: Volunteer dental students underwent spectrophotometric color assessment using the SpectroShade device. Two measurements were carried out (with the individuals’ occlusion closed and with the occlusion open) on 43 upper central and 58 lateral incisors. Association between colorimetric variables L*, a*, b* and ΔE00 and tooth width, length and tobacco usage were examined. Results: Slight changes in the CIELAB values between closed and open occlusions were found for both the gingival and the central sections as for the overall tooth area, with mean ΔL*=-1.24, Δa*=-1.77, Δb*=-1.42 and ΔE00=1,84. A larger difference was detected in the incisal area, with mean ΔL*=-2.99, Δa*=-1.76, Δb*=-2.83 and ΔE00=3.65. Conclusion: In conclusion, our study showed that dental occlusion does not play a significant role in tooth color matching determinations, even though attention to avoid overbite due to a maximum intercuspation should be made

Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy- relevant energies down to stopping

Track structures and resulting DNA damage in human cells have been simulated for hydrogen, helium, carbon, nitrogen, oxygen and neon ions with 0.25–256 MeV/u energy. The needed ion interaction cross sections have been scaled from those of hydrogen; Barkas scaling formula has been refined, extending its applicability down to about 10 keV/u, and validated against established stopping power data. Linear energy transfer (LET) has been scored from energy deposits in a cell nucleus; for very low-energy ions, it has been defined locally within thin slabs. The simulations show that protons and helium ions induce more DNA damage than heavier ions do at the same LET. With increasing LET, less DNA strand breaks are formed per unit dose, but due to their clustering the yields of double-strand breaks (DSB) increase, up to saturation around 300 keV/μm. Also individual DSB tend to cluster; DSB clusters peak around 500 keV/μm, while DSB multiplicities per cluster steadily increase with LET. Remarkably similar to patterns known from cell survival studies, LET-dependencies with pronounced maxima around 100– 200 keV/μm occur on nanometre scale for sites that contain one or more DSB, and on micrometre scale for megabasepair-sized DNA fragments

SOHLH1 and SOHLH2 control Kit expression during postnatal male germ cell development

How Kit expression is regulated in the germline remains unknown. SOHLH1 and SOHLH2, two bHLH transcription factors specifically expressed in germ cells, are involved in spermatogonia and oocyte differentiation. In the male, deletion of each factor causes loss of Kit-expressing spermatogonia in the prepuberal testis. In the female, SOHLH1 and SOHLH2 ablations cause oocyte loss in the neonatal ovary. To investigate whether Kit expression is regulated by these two factors in male germ cells, we examined SOHLH1 and SOHLH2 expression during fetal and postnatal mouse development. We found a strong positive correlation between Kit and the two transcription factors only in postnatal spermatogonia. SOHLH2 was enriched in undifferentiated spermatogonia, whereas SOHLH1 expression was maximal at Kit-dependent stages. Expression of SOHLH1, but not SOHLH2, was increased in postnatal mitotic germ cells by treatment with all-trans retinoic acid. We found that E-box sequences within the Kit promoter and its first intron can be transactivated in transfection experiments overexpressing Sohlh1 or Sohlh2. Co-transfection of both factors showed a cooperative effect. EMSA experiments showed that SOHLH1 and SOHLH2 can independently and cooperatively bind an E-box-containing probe. In vivo co-immunoprecipitations indicated that the two proteins interact and overexpression of both factors increases endogenous Kit expression in embryonic stem cells. SOHLH1 was found by ChIP analysis to occupy an E-box-containing region within the Kit promoter in spermatogonia chromatin. Our results suggest that SOHLH1 and SOHLH2 directly stimulate Kit transcription in postnatal spermatogonia, thus activating the signaling involved in spermatogonia differentiation and spermatogenetic progression