Structural MRI in Frontotemporal Dementia: Comparisons between Hippocampal Volumetry,Tensor-Based Morphometry and Voxel-Based Morphometry

Background

MRI is an important clinical tool for diagnosing dementia-like diseases such as Frontemporal Dementia (FTD). However there is a need to develop more accurate and standardized MRI analysis methods.

Objective

To compare FTD with Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) with three automatic MRI analysis methods - Hippocampal Volumetry (HV), Tensor-based Morphometry (TBM) and Voxel-based Morphometry (VBM), in specific regions of interest in order to determine the highest classification accuracy.

Methods

Thirty-seven patients with FTD, 46 patients with AD, 26 control subjects, 16 patients with progressive MCI (PMCI) and 48 patients with stable MCI (SMCI) were examined with HV, TBM for shape change, and VBM for gray matter density. We calculated the Correct Classification Rate (CCR), sensitivity (SS) and specificity (SP) between the study groups.

Results

We found unequivocal results differentiating controls from FTD with HV (hippocampus left side) (CCR = 0.83; SS = 0.84; SP = 0.80), with TBM (hippocampus and amygdala (CCR = 0.80/SS = 0.71/SP = 0.94), and with VBM (all the regions studied, especially in lateral ventricle frontal horn, central part and occipital horn) (CCR = 0.87/SS = 0.81/SP = 0.96). VBM achieved the highest accuracy in differentiating AD and FTD (CCR = 0.72/SS = 0.67/SP = 0.76), particularly in lateral ventricle (frontal horn, central part and occipital horn) (CCR = 0.73), whereas TBM in superior frontal gyrus also achieved a high accuracy (CCR = 0.71/SS = 0.68/SP = 0.73). TBM resulted in low accuracy (CCR = 0.62) in the differentiation of AD from FTD using all regions of interest, with similar results for HV (CCR = 0.55).

Conclusion

Hippocampal atrophy is present not only in AD but also in FTD. Of the methods used, VBM achieved the highest accuracy in its ability to differentiate between FTD and AD.     

Risk factors for post-weaning diarrhoea on piglet producing farms in Finland

Background  

Post-weaning diarrhoea (PWD) is a significant gastrointestinal disease in pigs. It is considered a multifactorial disease associated with proliferation of enterotoxigenic Escherichia coli in the intestinal tract of affected pigs. The aim of this study was to analyse risk factors related to the occurrence of PWD on Finnish piglet producing farms.     

Triacylglycerol fatty acid composition in diet-induced weight loss in subjects with abnormal glucose metabolism--the GENOBIN study

Background

The effect of weight loss on different plasma lipid subclasses at the molecular level is unknown. The aim of this study was to examine whether a diet-induced weight reduction result in changes in the extended plasma lipid profiles (lipidome) in subjects with features of metabolic syndrome in a 33-week intervention.

Methodology/Principal Findings

Plasma samples of 9 subjects in the weight reduction group and 10 subjects in the control group were analyzed using mass spectrometry based lipidomic and fatty acid analyses. Body weight decreased in the weight reduction group by 7.8±2.9% (p<0.01). Most of the serum triacylglycerols and phosphatidylcholines were reduced. The decrease in triacylglycerols affected predominantly the saturated short chain fatty acids. This decrease of saturated short chain fatty acid containing triacylglycerols correlated with the increase of insulin sensitivity. However, levels of several longer chain fatty acids, including arachidonic and docosahexanoic acid, were not affected by weight loss. Levels of other lipids known to be associated with obesity such as sphingolipids and lysophosphatidylcholines were not altered by weight reduction.

Conclusions/Significance

Diet-induced weight loss caused significant changes in global lipid profiles in subjects with abnormal glucose metabolism. The observed changes may affect insulin sensitivity and glucose metabolism in these subjects.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00621205","term_id":"NCT00621205"}}NCT00621205     

Comparison of rat epidermal keratinocyte organotypic culture (ROC) with intact human skin: Lipid composition and thermal phase behavior of the stratum corneum

The present report is a part of our continuing efforts to explore the utility of the rat epidermal keratinocyte organotypic culture (ROC) as an alternative model to human skin in transdermal drug delivery and skin irritation studies of new chemical entities and formulations. The aim of the present study was to compare the stratum corneum lipid content of ROC with the corresponding material from human skin. The lipid composition was determined by thin-layer chromatography (TLC) and mass-spectrometry, and the thermal phase transitions of stratum corneum were studied by differential scanning calorimetry (DSC). All major lipid classes of the stratum corneum were present in ROC in a similar ratio as found in human stratum corneum. Compared to human skin, the level of non-hydroxyacid-sphingosine ceramide (NS) was increased in ROC, while α-hydroxyacid-phytosphingosine ceramide (AP) and non-hydroxyacid-phytosphingosine ceramides (NP) were absent. Also some alterations in fatty acid profiles of ROC ceramides were noted, e.g., esterified ω-hydroxyacid-sphingosine contained increased levels of oleic acid instead of linoleic acid. The fraction of lipids covalently bound to corneocyte proteins was distinctly lower in ROC compared to human skin, in agreement with the results from DSC. ROC underwent a lipid lamellar order to disorder transition (T₂) at a slightly lower temperature (68 °C) than human skin (74 °C). These differences in stratum corneum lipid composition and the thermal phase transitions may explain the minor differences previously observed in drug permeation between ROC and human skin.     

Vitamin C enhances differentiation of a continuous keratinocyte cell line (REK) into epidermis with normal stratum corneum ultrastructure and functional permeability barrier

A continuous rat epidermal cell line (rat epidermal keratinocyte; REK) formed a morphologically well-organized epidermis in the absence of feeder cells when grown for 3 weeks on a collagen gel in culture inserts at an air-liquid interface, and developed a permeability barrier resembling that of human skin. By 2 weeks, an orthokeratinized epidermis evolved with the suprabasal layers exhibiting the differentiation markers keratin 10, involucrin, and filaggrin. Granular cells with keratohyalin granules and lamellar bodies, and corneocytes with cornified envelopes and tightly packed keratin filaments were present. Morphologically, vitamin C supplementation of the culture further enhanced the normal wavy pattern of the stratum corneum, the number of keratohyalin granules present, and the quantity and organization of intercellular lipid lamellae in the interstices of the stratum corneum. The morphological enhancements observed with vitamin C correlated with improved epidermal barrier function, as indicated by reduction of the permeation rates of tritiated corticosterone and mannitol, and transepidermal water loss, with values close to those of human skin. Moreover, filaggrin mRNA was increased by vitamin C, and western blots confirmed higher levels of profilaggrin and filaggrin, suggesting that vitamin C also influences keratinocyte differentiation in aspects other than the synthesis and organization of barrier lipids. The unique REK cell line in organotypic culture thus provides an easily maintained and reproducible model for studies on epidermal differentiation and transepidermal permeation.     

A meta‐analysis of nestedness and turnover components of beta diversity across organisms and ecosystems

Aim

The number of studies investigating the nestedness and turnover components of beta diversity has increased substantially, but our general understanding of the drivers of turnover and nestedness remains elusive. Here, we examined the effects of species traits, spatial extent, latitude and ecosystem type on the nestedness and turnover components of beta diversity.

Location

Global.

Time period

1968–2017.

Major taxa studied

From bacteria to mammals.

Methods

From the 99 studies that partition total beta diversity into its turnover and nestedness components, we assembled 269 and 259 data points for the pairwise and multiple site beta‐diversity metrics, respectively. Our data covered a broad variation in species dispersal type, body size and trophic position. The data were from freshwater, marine and terrestrial realms, and encompassed geographical areas from the tropics to near polar regions. We used linear modelling as a meta‐regression tool to analyse the data.

Results

Pairwise turnover, multiple site turnover and total beta diversity all decreased significantly with latitude. In contrast, multiple site nestedness showed a positive relationship with latitude. Beta‐diversity components did not generally differ among the realms. The turnover component and total beta diversity increased with spatial extent, whereas nestedness was scale invariant for pairwise metrics. Multiple site beta‐diversity components did not vary with spatial extent. Surprisingly, passively dispersed organisms had lower turnover and total beta diversity than flying organisms. Body size showed a relatively weak relationship with beta diversity but had important interactions with trophic position, thus also affecting beta diversity via interactive effects. Producers had significantly higher average pairwise turnover and total beta diversity than carnivores.

Main conclusions

The present results provide evidence that species turnover, being consistently the larger component of total beta diversity, and nestedness are related to the latitude of the study area and intrinsic organismal features. We showed that two beta‐diversity components had generally opposing patterns with regard to latitude. We highlight that beta‐diversity partition may give additional insights into the underlying causes of spatial variability in biotic communities compared with total beta diversity alone.     

Activity and stability of human kallikrein-2-specific linear and cyclic peptide inhibitors.

Human glandular kallikrein (KLK2) is a highly prostate-specific serine protease, which is mainly excreted into the seminal fluid, but part of which is also secreted into circulation from prostatic tumors. Since the expression level of KLK2 is elevated in aggressive tumors and it has been suggested to mediate the metastasis of prostate cancer, inhibition of the proteolytic activity of KLK2 is of potential therapeutic value. We have previously identified several KLK2-specific linear peptides by phage display technology. Two of its synthetic analogs, A R R P A P A P G (KLK2a) and G A A R F K V W W A A G (KLK2b), show specific inhibition of KLK2 but their sensitivity to proteolysis in vivo may restrict their potential use as therapeutic agents. In order to improve the stability of the linear peptides for in vivo use, we have prepared cyclic analogs and compared their biological activity and their structural stability. A series of cyclic variants with cysteine bridges were synthesized. Cyclization inactivated one peptide (KLK2a) and its derivatives, while the other peptide (KLK2b) and its derivatives remained active. Furthermore, backbone cyclization of KLK2b improved significantly the resistance against proteolysis by trypsin and human plasma. Nuclear magnetic resonance studies showed that cyclization of the KLK2b peptides does not make the structures more rigid. In conclusion, we have shown that backbone cyclization of KLK2 inhibitory peptides can be used to increase stability without losing biological activity. This should render the peptides more useful for in vivo applications, such as tumor imaging and prostate cancer targeting.     

Local environment and connectivity are the main drivers of diatom species composition and trait variation in a set of tropical reservoirs

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Relationships between local population persistence, local abundance and regional occupancy of species: distribution patterns of diatoms in boreal streams

Aims We have two aims: (1) to examine the relationship between local population persistence, local abundance and regional occupancy of stream diatoms and (2) to characterize the form of the species–occupancy frequency distribution of stream diatoms. Location Boreal streams in Finland. There were three spatial extents: (1) across ecoregions in Finland, (2) within ecoregions in Finland, and (3) within a single drainage system in southern Finland. Methods Diatoms were sampled from stones (epilithon), sediment (epipelon) and aquatic plants (epiphyton) in streams using standardized sampling methods. To assess population persistence, diatom sampling was conducted monthly at four stream sites from June to October. The relationships between local population persistence, local abundance and regional occupancy were examined using correlation analyses. Results There was a significant positive relationship between local persistence and abundance of diatoms in epilithon, epipelon and epiphyton. Furthermore, local abundance and regional occupancy showed a significant positive relationship at multiple spatial extents; that is, across ecoregions, within ecoregions and within a drainage system. The relationships between occupancy and abundance did not differ appreciably among impacted and near pristine‐reference sites. The occupancy–frequency distribution was characterized by a large number of satellite species which occurred at only a few sites, whereas core species that occurred at most sites were virtually absent. Main conclusions The positive relationship between local population persistence and abundance suggested that a high local abundance may prevent local extinction or that high persistence is facilitated by a high local cell density. High local persistence and local abundance may also positively affect the degree of regional occupancy in stream diatoms. The results further showed that anthropogenic effects were probably too weak to bias the relationship between occupancy and abundance, or that the effects have already modified the distribution patterns of stream diatoms. The small number of core species in the species–occupancy frequency distribution suggested that the regional distribution patterns of stream diatoms, or perhaps unicellular microbial organisms in general, may not be fundamentally different from those described previously for multicellular organisms, mainly in terrestrial environments, although average global range sizes may differ sharply between these two broad groups of organisms.