Years of life that could be saved from prevention of hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour 65 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost

The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex

Capacitative Ca2+ Entry Is Closely Linked to the Filling State of Internal Ca2+ Stores: A Study Using Simultaneous Measurements of ICRAC and Intraluminal [Ca2+]

ICRAC (the best characterized Ca2+ current activated by store depletion) was monitored concurrently for the first time with [Ca2+] changes in internal stores. To establish the quantitative and kinetic relationship between these two parameters, we have developed a novel means to clamp [Ca2+] within stores of intact cells at any level. The advantage of this approach, which is based on the membrane-permeant low-affinity Ca2+ chelator N,N,N′,N′-tetrakis (2-pyridylmethyl)ethylene diamine (TPEN), is that [Ca2+] within the ER can be lowered and restored to its original level within 10–15 s without modifications of Ca2+ pumps or release channels. Using these new tools, we demonstrate here that Ca2+ release–activated Ca2+ current (ICRAC) is activated (a) solely by reduction of free [Ca2+] within the ER and (b) by any measurable decrease in [Ca2+]ER. We also demonstrate that the intrinsic kinetics of inactivation are relatively slow and possibly dependent on soluble factors that are lost during the whole-cell recording

Guidelines on experimental methods to assess mitochondrial dysfunction in cellular models of neurodegenerative diseases

Neurodegenerative diseases are a spectrum of chronic, debilitating disorders characterised by the progressive degeneration and death of neurons. Mitochondrial dysfunction has been implicated in most neurodegenerative diseases, but in many instances it is unclear whether such dysfunction is a cause or an effect of the underlying pathology, and whether it represents a viable therapeutic target. It is therefore imperative to utilise and optimise cellular models and experimental techniques appropriate to determine the contribution of mitochondrial dysfunction to neurodegenerative disease phenotypes. In this consensus article, we collate details on and discuss pitfalls of existing experimental approaches to assess mitochondrial function in in vitro cellular models of neurodegenerative diseases, including specific protocols for the measurement of oxygen consumption rate in primary neuron cultures, and single-neuron, time-lapse fluorescence imaging of the mitochondrial membrane potential and mitochondrial NAD(P)H. As part of the Cellular Bioenergetics of Neurodegenerative Diseases (CeBioND) consortium ( www.cebiond.org ), we are performing cross-disease analyses to identify common and distinct molecular mechanisms involved in mitochondrial bioenergetic dysfunction in cellular models of Alzheimer's, Parkinson's, and Huntington's diseases. Here we provide detailed guidelines and protocols as standardised across the five collaborating laboratories of the CeBioND consortium, with additional contributions from other experts in the field

Qualitative evaluation of the effects of professional oral hygiene instruments on prosthetic ceramic surfaces

During professional hygiene procedures, different instruments used may cause various damage to dental prostheses. Deplaquing and scaling with curettes and ultrasonic instruments may inadvertently increase the surface roughness of the material and the risk of future bacterial adhesion and/or also compromise the marginal seal of the prosthesis. Hence, the aim of this study was to assess the qualitative effects of two types of curettes and one piezoelectric instrument with a stain-less-steel tip on three types of metal-free samples. After treating the samples with different instru-mentations, they were analyzed using the scanning electron microscope and then underwent a qualitative microanalysis by using a spectroscopy machine. All the materials tested in this study have undergone significant changes of their superficial structure after instrumentation both with mechanical and manual instruments. Plastic curettes appeared to be less aggressive than the other in-struments. Disilicate samples show a significantly lower degree of surface glazing erosion com-pared to the zirconia sample with all the instruments used

Ca2+ Homeostasis in the Agonist-sensitive Internal Store: Functional Interactions Between Mitochondria and the ER Measured In Situ in Intact Cells

Mitochondria have a well-established capacity to detect cytoplasmic Ca2+ signals resulting from the discharge of ER Ca2+ stores. Conversely, both the buffering of released Ca2+ and ATP production by mitochondria are predicted to influence ER Ca2+ handling, but this complex exchange has been difficult to assess in situ using conventional measurement techniques. Here we have examined this interaction in single intact BHK-21 cells by monitoring intraluminal ER [Ca2+] directly using trapped fluorescent low-affinity Ca2+ indicators. Treatment with mitochondrial inhibitors (FCCP, antimycin A, oligomycin, and rotenone) dramatically prolonged the refilling of stores after release with bradykinin. This effect was largely due to inhibition of Ca2+ entry pathways at the plasma membrane, but a significant component appears to arise from reduction of SERCA-mediated Ca2+ uptake, possibly as a consequence of ATP depletions in a localized subcellular domain. The rate of bradykinin-induced Ca2+ release was reduced to 51% of control by FCCP. This effect was largely overcome by loading cells with BAPTA-AM, highlighting the importance of mitochondrial Ca2+ buffering in shaping the release kinetics. However, mitochondria-specific ATP production was also a significant determinant of the release dynamic. Our data emphasize the localized nature of the interaction between these organelles, and show that competent mitochondria are essential for generating explosive Ca2+ signals

Evaluation of Load Distribution in a Mandibular Model with Four Implants Depending on the Number of Prosthetic Screws Used for OT-Bridge System: A Finite Element Analysis (FEA)

In full-arch implant rehabilitations, when the anterior screw abutment channel compromises the aesthetic of the patient, the OT-Bridge system used with its Seeger rings may provide the necessary retention of the prosthesis. However, no studies have evaluated the forces generated at the Seeger level during loading. This Finite Element Analysis aims to investigate the mechanical behavior of Seeger rings in a mandibular model with four implants and an OT-Bridge system, used without one or two anterior prosthetic screws. A 400 N unilateral load was virtually applied on a 7 mm distal cantilever. Two different variables were considered: the constraint conditions using two or three screws instead of four and the three different framework materials (fiberglass reinforced resin, cobalt-chrome, TiAl6V4). The FEA analysis exhibited tensile and compressive forces on the Seeger closest to the loading point. With the resin framework, a tension force on abutment 3.3 generates a displacement from 5 to 10 times greater than that respectively expressed in metal framework materials. In a full-arch rehabilitation with four implants, the case with three prosthetic screws seems to be a safer and more predictable configuration instead of two. Considering the stress value exhibited and the mechanical properties of the Seeger, the presence of only two prosthetic screws could lead to permanent deformation of the Seeger in the screwless abutment closest to the loading point

Assessment of Preload Loss after Cyclic Loading in the OT Bridge System in an “All-on-Four” Rehabilitation Model in the Absence of One and Two Prosthesis Screws

The aim of this study was to evaluate the stability of prosthetic screws after applying cyclic loadings in an “all-on-four” rehabilitation model with the OT Bridge system. The model was tested both with and without anterior screws. Four implant analogues following the “all-on-four” concept were inserted in an edentulous mandibular resin model. An OT Bridge system with a Cr–Co prosthetic framework was fabricated. Depending on the presence or absence of one or two anterior screws on the implant analogues, three groups were created, i.e., Gr.1: three tightening screws, Gr.2: two tightening screws, Control Group: four tightening screws. Each single group underwent subsequent 400,000 cyclic loads, simulating approximately a year of chewing by using a dynamometer machine. This cycle was repeated five times for each group, and preload loss values were evaluated on each prosthetic screw after each cycle. All the data obtained were analyzed by one-way ANOVA and Student’s t-test. No statistically significant differences after intragroup analysis were found. A statistically significant difference within the Gr.1 between the screws in positions 33 and 36, equal to 15.2% (p-value = 0.0176), was found. The OT Bridge seems a useful system to maintain the retention of a prosthesis during mechanical stress conditions even in the absence of one screw in an “all-on-four” rehabilitation. This could represent a good solution to solve the esthetic problem of the screw buccal access hole for fixed solutions

Editorial: Evolution in respiratory pharmacology

This collection of Research Topics entitled “Evolution in respiratory pharmacology,” involving authors from several countries, confirms that “Respiratory Pharmacology” is a current topic in clinical and research settings. All articles focused on contributions that explore the changing context and emerging new perspectives within Respiratory Pharmacology (Kim et al., Cerqua et al., Li et al., Lin et al., Zhang et al.). The emphasis of this Research Topic is on the dynamics of change and the evolution of the latest progress made in the field of Respiratory Pharmacology. This collection of articles aims to inform, inspire, and provide direction and guidance to researchers in the field