High levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the serum are associated with poor prognosis in HPV-negative squamous cell oropharyngeal cancer

Background: An emerging subset of oropharyngeal squamous cell carcinomas (OPSCC) is caused by HPV. HPV-positive OPSCC has a better prognosis than HPV-negative OPSCC, but other prognostic markers for these two different diseases are scarce. Our aim was to evaluate serum levels and tumor expression of matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and to assess their prognostic role in HPV-positive and HPV-negative OPSCC. Materials and methods: A total of 90 consecutive OPSCC patients diagnosed and treated with curative intent at the Helsinki University Hospital between 2012 and 2016 were included. Serum samples were prospectively collected. An immunofluorometric assay and an enzyme-linked immunosorbent assay were used to determine MMP-8 and TIMP-1 serum concentrations, respectively. HPV status of the tumors was determined using a combination of HPV-DNA genotyping and p16-INK4a immunohistochemistry. The endpoints were overall survival (OS) and disease-free survival (DFS). Results: High TIMP-1 serum levels were strongly and independently associated with poorer OS (adjusted HR 14.7, 95% CI 1.8-117.4, p = 0.011) and DFS (adjusted HR 8.7, 95% CI 1.3-57.1, p = 0.024) among HPV-negative patients; this association was not observed in HPV-positive OPSCC. Although TIMP-1 was immunoexpressed in the majority of the tumor tissue samples, the level of immunoexpression was not associated with prognosis, nor did MMP-8 serum levels. Conclusion: Our results indicate that serum TIMP-1 levels may serve as an independent prognostic marker for HPV-negative OPSCC patients.</div

Geographic Information Systems (GIS) in Assessing Dental Health

The present study investigated the distribution profile of dental caries and its association with areas of social deprivation at the individual and contextual level. The cluster sample consisted of 1,002 12-year-old schoolchildren from Piracicaba, SP, Brazil. The DMFT Index was used for dental caries and the Care Index was used to determine access to dental services. On the individual level, variables were associated with a better oral status. On the contextual level, areas were not associated with oral status. However, maps enabled determining that the central districts have better social and oral conditions than the deprived outlying districts

A2ML1 and otitis media: novel variants, differential expression, and relevant pathways

A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media. Sixteen novel, damaging A2ML1 variants identified in otitis media patients were rare or low-frequency in population-matched controls. In the indigenous population, both gingivitis and A2ML1 variants including the known duplication variant and the novel splice variant c.4061 + 1 G>C were independently associated with otitis media. Sequencing of salivary RNA samples from indigenous Filipinos demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants. Sequencing of additional salivary RNA samples from US patients with otitis media revealed differentially expressed genes that are highly correlated with A2ML1 expression levels. In particular, RND3 is upregulated in both A2ML1 variant carriers and high-A2ML1 expressors. These findings support a role for A2ML1 in keratinocyte differentiation within the middle ear as part of otitis media pathology and the potential application of ROCK inhibition in otitis media

IGS-RFLP analysis and development of molecular markers for identification of Fusarium poae, Fusarium langsethiae, Fusarium sporotrichioides and Fusarium kyushuense

The intergenic spacer (IGS) regions of the rDNA of several Fusarium spp. strains obtained from the collaborative researchers (Int. J. Food Microbiol. (2003)) were amplified by polymerase chain reaction (PCR), and an IGS¿RFLP analysis was performed. Restriction digestion with AluI, MspI and PstI allowed differentiation between the related Fusarium poae and Fusarium kyushuense species. Fusarium langsethiae was also separated from Fusarium sporotrichioides (including var. minus) on the basis of the banding patterns after MspI digestion, while specific XhoI, AluI and MspI restriction patterns were found in the IGS amplicons of F. sporotrichioides var. minus. According to the phylogenetic analysis of IGS¿RFLP patterns, F. langsethiae (except for one strain), F. sporotrichioides, F. poae and F. kyushuense strains formed four well-supported clades with high-bootstrap values. Based on the sequence differences in the IGS region, species-specific primers were designed for the F. langsethiae/F. sporotrichioides group and for F. poae. The specificity and sensitivity of the primers were tested on various Fusarium species and isolates, and on several other important fungal genera associated with cereals. The F. poae-specific primers, designed in this study, showed the same specificity as primers Fp82f/Fp82r developed previously. The two phylogenetic subgroups of F. langsethiae, found by IGS sequencing analysis, were separated on the basis of size differences of the amplification products with primers CNL12/PulvIGSr specific for the F. langsethiae/F. sporotrichioides group. RFLP analysis of the amplified IGS region is a useful molecular assay for characterisation and a phylogenetic study of several related Fusarium species¿F. langsethiae, F. sporotrichioides, F. sporotrichioides var. minus, F. poae and F. kyushuense. The primers designed in this study were highly specific and allowed identification of F. poae and the F. langsethiae/F. sporotrichioides group

Fluid-mediated, brittle-ductile cyclicity at seismogenic depth: Fluid record and deformation history of a fault system of the Svecofennian basement in SW Finland

Crustal deformation and fluid flow at the brittle-ductile transition zone (BDTZ) are closely related and reciprocally dependent during repeating and transient cycles of frictional and viscous deformation. Despite numerous studies documenting in detail seismogenic faults exhumed from the BDTZ, uncertainties remain as to the role of fluids in facilitating broadly coeval brittle and ductile deformation at that structural level. We present the results of a multi-scale and multi-technique study that allowed us to reconstruct the temporal variations in fluid pressure, temperature, and bulk composition of the fluids that mediated deformation and steered strain localization within a strike-slip fault originally active at the BDTZ under overall ductile conditions. The studied fault zone is hosted in the Paleoproterozoic Svecofennian basement of SW Finland. The fault core is characterized by two synkinematic and laterally continuous quartz-chlorite veins formed by two texturally distinct types of quartz – Qtz I and Qtz II, with Qtz I older than Qtz II. Meso- and microstructural analysis combined with fluid compositional data indicate recurrent cycles of mutually overprinting brittle and ductile deformation. Geochemical data from fault-minerals and the fluid inclusion study indicate that the two distinct quartz types precipitated from different fluid batches with a fluid bulk salinity in the 0-11 wt% NaCleq range. Quartz-chlorite and sphalerite-stannite geothermometry indicates that the temperature of the fluids involved in the deformation evolved through time from &gt; 350 °C during Qtz I precipitation to &lt; 300 °C at the time of Qtz II crystallization. The peak fluid pressure estimates constrain pore pressure oscillations between 80 and 210 MPa during the recorded faulting episodes. Initial, fluid-mediated embrittlement of the crystalline basement at the BDTZ generated a diffuse network of joints and/or hybrid/shear fractures in the damage zone; subsequent strain accommodation led to more localized deformation within the fault core

Evidence of low-temperature plasticity in naturally deformed pyrite: a LA-ICP-TOFMS-EBSD combined approach (Olkiluoto Island, Finland)

Knowledge of active slip systems and element distribution in deforming minerals is important in understanding deformation processes. Pyrite is such a common mineral in many ore deposits (e.g. auriferous deposits) and in shear zones that a detailed understanding of the mechanisms steering its deformation is necessary. Due to its resistant, pyrite commonly preserves microstructural evidence of both brittle and low-temperature crystal-plastic deformation. The study of intragrain sub-structures within naturally deformed pyrite grains offers the potential, therefore, to investigate the remobilization of chemical elements within the crystal lattice induced by strain. In this study, we combine microstructural observations by electron back-scattered diffraction analysis (EBSD) with pyrite elemental mapping by laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS) to study crystal plastic deformation and element mobility in pyrite from a naturally deformed quartz-sulphide vein associated with a strike-slip fault that cyclically experienced transient differential stress and pore pressure oscillations. Initially, LA-ICP-TOFMS imaging was used to image sets of otherwise invisible intragrain sub-structures as highlighted by the structurally controlled accumulation of specific elements (e.g. Co, Ni, Cu, Sn, Ag, As, Sb, Pb). EBSD analysis was subsequently performed in the areas analysed by TOFMS with the aim to study the nature of the intragrain sub-structures. EBSD data show that these chemically defined intragrain sub-structures correspond to low-angle boundaries. Cumulative misorientation profiles across pyrite grains suggest that low-angle boundaries are both related to healed fractures and growth features but also indicate a continuous cumulative lattice misorientation up to &gt;5°. Boundary trace analysis suggests that fracturing is competing with tilt boundary rotation and pressure-solution to accommodate strain and locally concentrate specific chemical elements