Perioperative and early postoperative neurological deficit in older patients during carotid artery thrombendarterectomy

Cerebrovascular accidents, strokes in particular, are among the most frequent causes of death today in developed countries. In the last two decades, stroke was the second most frequent cause of death in Primorsko-Goranska Region in Croatia. In older patients, individuals older than 65 years of age have an increased risk of stroke, mainly because the degree of carotid artery stenosis increases with age. The most frequent complication of the high percent stenosis of the carotid arteries is thrombosis in the area of atherosclerotic changes of blood vessels. With the increase in the age of the population, there is also an increase in the number of risk factors of cerebrovascular accident. Doppler ultrasound sonography and Multi Slice CT scans have the most prominent role in the early detection of atherosclerotic changes and in the assessment of the degree of carotid artery narrowing. Today, in Croatia as well as worldwide, thrombendarterectomy holds the most important place in stroke prevention. Between 2006 and 2009, 209 patients underwent surgical intervention at the Clinical Hospital Center in Rijeka for high degree of carotid artery narrowing. In the group younger than 65 years of age, which consisted of 53 patients, a neurological deficit was noted in 4 patients (7.54%) in the perioperative and early postoperative course. In the group of individuals older than 65 years of age, which consisted of 156 patients, a neurological deficit was noted in 9 patients (5.76%). There was no significant statistical difference in the incidence of neurological deficit, nor in the mortality in individuals older than 65 years of age during carotid arteries thrombendarterectomy.     

Response of antioxidant defense system to chromium (VI)-induced cytotoxicity in human diploid cells

The aim of this study is to establish antioxidant indicators of chromium toxicity in fetal human lung fibroblasts (HLF). The results obtained corroborate and develop our earlier observation of low-dose and long-term action of Cr(VI) on human cells in culture. In the case of a nontoxic chromium dose, temporary oxidative stress is overcome by increased activity of the antioxidant system with correlation to cell cycle re-entry. The toxic concentrations misbalance the cell antioxidant defense systems and cause irreversible growth arrest and massive cell death by apoptosis. Sub-toxicity is defined as toxicity stretched in time. The activity of GPx (glutathione peroxidase) is proposed as a biomarker of oxidative stress caused by Cr(VI), and the GR (glutathione reductase) inhibition is considered as a marker of the toxicity developed under the complex Cr(VI) action. In HLF cells the glutathione dependent defense system is the first system destroyed in response to toxic chromium action. Only the balance between SOD (superoxide dismutase) and H₂O₂ degrading enzymes (catalase and GPx), should play an important role in the fate of a cell, not individual enzymes.     

Changes of the GPR17 receptor, a new target for neurorepair, in neurons and glial cells in patients with traumatic brain injury

Unveiling the mechanisms participating in the damage and repair of traumatic brain injury (TBI) is fundamental to develop new therapies. The P2Y-like GPR17 receptor has recently emerged as a sensor of damage and a key actor in lesion remodeling/repair in the rodent brain, but its role in humans is totally unknown. Here, we characterized GPR17 expression in brain specimens from seven intensive care unit TBI patients undergoing neurosurgery for contusion removal and from 28 autoptic TBI cases (and 10 control subjects of matched age and gender) of two university hospitals. In both neurosurgery and autoptic samples, GPR17 expression was strong inside the contused core and progressively declined distally according to a spatio-temporal gradient. Inside and around the core, GPR17 labeled dying neurons, reactive astrocytes, and activated microglia/macrophages. In peri-contused parenchyma, GPR17 decorated oligodendrocyte precursor cells (OPCs) some of which had proliferated, indicating re-myelination attempts. In autoptic cases, GPR17 expression positively correlated with death for intracranial complications and negatively correlated with patients’ post-traumatic survival. Data indicate lesion-specific sequential involvement of GPR17 in the (a) death of irreversibly damaged neurons, (b) activation of microglia/macrophages remodeling the lesion, and (c) activation/proliferation of multipotent parenchymal progenitors (both reactive astrocytes and OPCs) starting repair processes. Data validate GPR17 as a target for neurorepair and are particularly relevant to setting up new therapies for TBI patients.     

Lacertoid Footprints of the Upper Permian Arenaria di Val Gardena Formation (Northern Italy)

Lacertoid footprints are the largest component of the Upper Permian Arenaria di Val Gardena Formation ichnofauna that contains hundreds of specimens mostly referred to the ichnogenus Rhynchosauroides Maidwell 1911. In this paper, we analyzed unpublished material and re-examined the Rhynchosauroides footprints of that ichnofauna, in particular the figured specimens. Analysis of Rhynchosauroides and its type ichnospecies R. rectipes Maidwell 1911 was first necessary. This preliminary investigation highlighted several problems, including ichnospecies named on the basis of poorly preserved material and in some cases significantly different from the type ichnospecies.

The study allowed for recognition of three ichnotaxa referred to Rhynchosauroides: Rhynchosauroides pallinii Conti et al., 1977, Rhynchosauroides isp.1 and Rhynchosauroides isp.2 and Ganasauripus ladinus igen. et isp. nov. Other material previously referred to Rhynchosauroides is herein regarded as unclassifiable, in the light of present ichnological knowledge and procedures.     

Combined Species Identification, Genotyping, and Drug Resistance Detection of Mycobacterium tuberculosis Cultures by MLPA on a Bead-Based Array

The population structure of Mycobacterium tuberculosis is typically clonal therefore genotypic lineages can be unequivocally identified by characteristic markers such as mutations or genomic deletions. In addition, drug resistance is mainly mediated by mutations. These issues make multiplexed detection of selected mutations potentially a very powerful tool to characterise Mycobacterium tuberculosis. We used Multiplex Ligation-dependent Probe Amplification (MLPA) to screen for dispersed mutations, which can be successfully applied to Mycobacterium tuberculosis as was previously shown. Here we selected 47 discriminative and informative markers and designed MLPA probes accordingly to allow analysis with a liquid bead array and robust reader (Luminex MAGPIX technology). To validate the bead-based MLPA, we screened a panel of 88 selected strains, previously characterised by other methods with the developed multiplex assay using automated positive and negative calling. In total 3059 characteristics were screened and 3034 (99.2%) were consistent with previous molecular characterizations, of which 2056 (67.2%) were directly supported by other molecular methods, and 978 (32.0%) were consistent with but not directly supported by previous molecular characterizations. Results directly conflicting or inconsistent with previous methods, were obtained for 25 (0.8%) of the characteristics tested. Here we report the validation of the bead-based MLPA and demonstrate its potential to simultaneously identify a range of drug resistance markers, discriminate the species within the Mycobacterium tuberculosis complex, determine the genetic lineage and detect and identify the clinically most relevant non-tuberculous mycobacterial species. The detection of multiple genetic markers in clinically derived Mycobacterium tuberculosis strains with a multiplex assay could reduce the number of TB-dedicated screening methods needed for full characterization. Additionally, as a proportion of the markers screened are specific to certain Mycobacterium tuberculosis lineages each profile can be checked for internal consistency. Strain characterization can allow selection of appropriate treatment and thereby improve treatment outcome and patient management.     

Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population

Background

Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes.

Objectives

We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures.

Methods

For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV₁), FEV₁ over forced vital capacity (FEV₁/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF_25-75) was regressed on interval exposure to particulate matter <10 µm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (p_interaction<0.05). Replication was attempted for SNPs with MAF>10% in 3320 SAPALDIA participants without GWAS.

Results

On the SNP-level, rs2035268 in gene SNCA accelerated FEV₁/FVC decline by 3.8% (p_interaction = 2.5×10⁻⁶), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml p_interaction = 9.7×10⁻⁸) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (p_interaction = 3.0×10⁻⁴) on FEV₁/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful.

Conclusions

Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobacco smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challenging.     

Detection of a second novel gammaherpesvirus in a free-ranging koala (Phascolarctos cinereus)

A second novel gammaherpesvirus was detected in a free-ranging koala (Phascolarctos cinereus) shown previously to be infected with phascolarctid herpesvirus 1. Analysis of the DNA polymerase gene showed that the virus was genetically distinct from all known gammaherpesviruses. This is the first reported dual gammaherpesvirus infection in an Australian marsupial.     

Selected acute phase CSF factors in ischemic stroke: findings and prognostic value

Background  

Study aimed at investigation of pathogenic role and prognostic value of several selected cerebrospinal fluid acute phase factors that can reflect the severity of ischemic brain damage.