86 research outputs found
Towards a representative reference for MRI-based human axon radius assessment using light microscopy
Non-invasive assessment of axon radii via MRI bears great potential for clinical and neuroscience research as it is a main determinant of the neuronal conduction velocity. However, there is a lack of representative histological reference data at the scale of the cross-section of MRI voxels for validating the MRI-visible, effective radius (reff). Because the current gold standard stems from neuroanatomical studies designed to estimate the bulk-determined arithmetic mean radius (rarith) on small ensembles of axons, it is unsuited to estimate the tail-weighted reff. We propose CNN-based segmentation on high-resolution, large-scale light microscopy (lsLM) data to generate a representative reference for reff. In a human corpus callosum, we assessed estimation accuracy and bias of rarith and reff. Furthermore, we investigated whether mapping anatomy-related variation of rarith and reff is confounded by low-frequency variation of the image intensity, e.g., due to staining heterogeneity. Finally, we analyzed the error due to outstandingly large axons in reff. Compared to rarith, reff was estimated with higher accuracy (maximum normalized-root-mean-square-error of reff: 8.5 %; rarith: 19.5 %) and lower bias (maximum absolute normalized-mean-bias-error of reff: 4.8 %; rarith: 13.4 %). While rarith was confounded by variation of the image intensity, variation of reff seemed anatomy-related. The largest axons contributed between 0.8 % and 2.9 % to reff. In conclusion, the proposed method is a step towards representatively estimating reff at MRI voxel resolution. Further investigations are required to assess generalization to other brains and brain areas with different axon radii distributions
Comparison of insulin detemir and insulin glargine in subjects with type 1 diabetes using intensive insulin therapy
WSTĘP. Celem niniejszej pracy było porównanie kontroli
glikemii oraz ryzyka hipoglikemii podczas stosowania
insuliny detemir 2 × dziennie lub glarginy
raz dziennie u chorych na cukrzycę typu 1.
MATERIAŁ I METODY. Podczas trwającego 26 tygodni
wieloośrodkowego, otwartego badania z grupami
równoległymi 320 chorym na cukrzycę typu 1
podawano albo insulinę detemir 2 × dziennie albo
glarginę raz dziennie, każdorazowo w połączeniu
z przedposiłkowymi iniekcjami insuliny aspart.
WYNIKI. Po 26 tygodniach wartość HbA1c zmniejszyła
się z 8,8% do 8,2% w grupie przyjmującej insulinę
detemir i z 8,7% do 8,2% w grupie leczonej glarginą.
Wartość stężenia glukozy w osoczu (PG) mierzonego
na czczo w domu była niższa podczas stosowania
glarginy niż w czasie podawania insuliny detemir (7,0 mmol/l vs. 7,7 mmol/l; p < 0,001). Ogólny
9-punktowy profil mierzonych w domu wartości glikemii
był porównywalny między grupami (p = 0,125).
Nie stwierdzono istotnej różnicy w zmienności pomiarów
PG u 1 pacjenta (p = 0,437). Zróżnicowanie
pomiarów przedposiłkowego stężenia PG u 1 badanego
było niższe podczas stosowania insuliny detemir
niż glarginy (p < 0,05). Ogólne ryzyko hipoglikemii
było podobne, nie stwierdzono różnic w występowaniu
potwierdzonych epizodów hipoglikemii. Ryzyko
silnej, nocnej hipoglikemii wynosiło odpowiednio:
72% i 32% i było niższe w grupie stosującej insulinę
detemir (p < 0,05). Zwiększenie masy ciała
nie różniło się znacząco między grupami przyjmującymi
insulinę detemir i glarginę (0,52 kg vs. 0,96 kg;
p = 0,193).
WNIOSKI. Leczenie insuliną detemir podawaną 2 × dziennie lub glarginą podawaną raz dziennie, każdorazowo
w połączeniu z insuliną aspart, powodowało
podobną kontrolę glikemii. Ogólne zagrożenie
hipoglikemią było porównywalne, natomiast
ryzyko nasilonej i nocnej hipoglikemii było istotnie
niższe podczas stosowania insuliny detemir.BACKGROUND. To compare glycaemic control and risk
of hypoglycaemia of twice-daily insulin detemir with
once-daily insulin glargine in subjects with type 1
diabetes.
MATERIAL AND METHODS. In this 26-week, multicentre,
open-label, parallel-group trial, 320 subjects
with type 1 diabetes received either insulin detemir
twice daily or insulin glargine once daily, each in
combination with premeal insulin aspart.
RESULTS. After 26 weeks, HbA1c had decreased from
8.8 to 8.2% in the insulin detemir group and from
8.7% to 8.2% in the insulin glargine group. Homemeasured
fasting plasma glucose (PG) was lower
with insulin glargine than with insulin detemir
(7.0 mmol/l vs. 7.7 mmol/l; p < 0.001). The overall
shape of the home-measured nine-point PG profiles
was comparable between treatments (p = 0.125).
Overall, there was no significant difference in
within-subject variation in PG (p = 0.437). Withinsubject
variation in predinner PG was lower with insulin
detemir than with insulin glargine (p < 0.05).
The overall risk of hypoglycaemia was similar with
no differences in confirmed hypoglycaemia. However,
the risk of severe and nocturnal hypoglycaemia
was 72% and 32%, respectively, lower with insulin detemir
than with insulin glargine (p < 0.05). Body weight
gain was not significantly different comparing
insulin detemir and insulin glargine (0.52 kg
vs. 0.96 kg, p = 0.193).
CONCLUSIONS. Treatment with twice-daily insulin
detemir or once-daily insulin glargine, each in combination
with insulin aspart, resulted in similar glycaemic
control. The overall risk of hypoglycaemia
was comparable, whereas the risks of both severe
and nocturnal hypoglycaemia were significantly lower
with insulin detemir
Metagenomics-based proficiency test of smoked salmon spiked with a mock community
An inter-laboratory proficiency test was organized to assess the ability of participants to perform shotgun metagenomic sequencing of cold smoked salmon, experimentally spiked with a mock community composed of six bacteria, one parasite, one yeast, one DNA, and two RNA viruses. Each participant applied its in-house wet-lab workflow(s) to obtain the metagenomic dataset(s), which were then collected and analyzed using MG-RAST. A total of 27 datasets were analyzed. Sample pre-processing, DNA extraction protocol, library preparation kit, and sequencing platform, influenced the abundance of specific microorganisms of the mock community. Our results highlight that despite differences in wet-lab protocols, the reads corresponding to the mock community members spiked in the cold smoked salmon, were both detected and quantified in terms of relative abundance, in the metagenomic datasets, proving the suitability of shotgun metagenomic sequencing as a genomic tool to detect microorganisms belonging to different domains in the same food matrix. The implementation of standardized wet-lab protocols would highly facilitate the comparability of shotgun metagenomic sequencing dataset across laboratories and sectors. Moreover, there is a need for clearly defining a sequencing reads threshold, to consider pathogens as detected or undetected in a food sample
Effect of skin infiltration with ropivacaine on postoperative pain in patients undergoing craniotomy
Signature-Tagged Mutagenesis in a Chicken Infection Model Leads to the Identification of a Novel Avian Pathogenic Escherichia coli Fimbrial Adhesin
The extraintestinal pathogen, avian pathogenic E. coli (APEC), known to cause systemic infections in chickens, is responsible for large economic losses in the poultry industry worldwide. In order to identify genes involved in the early essential stages of pathogenesis, namely adhesion and colonization, Signature-tagged mutagenesis (STM) was applied to a previously established lung colonization model of infection by generating and screening a total of 1,800 mutants of an APEC strain IMT5155 (O2:K1:H5; Sequence type complex 95). The study led to the identification of new genes of interest, including two adhesins, one of which coded for a novel APEC fimbrial adhesin (Yqi) not described for its role in APEC pathogenesis to date. Its gene product has been temporarily designated ExPEC Adhesin I (EA/I) until the adhesin-specific receptor is identified. Deletion of the ExPEC adhesin I gene resulted in reduced colonization ability by APEC strain IMT5155 both in vitro and in vivo. Furthermore, complementation of the adhesin gene restored its ability to colonize epithelial cells in vitro. The ExPEC adhesin I protein was successfully expressed in vitro. Electron microscopy of an afimbriate strain E. coli AAEC189 over-expressed with the putative EA/I gene cluster revealed short fimbrial-like appendages protruding out of the bacterial outer membrane. We observed that this adhesin coding gene yqi is prevalent among extraintestinal pathogenic E. coli (ExPEC) isolates, including APEC (54.4%), uropathogenic E. coli (UPEC) (65.9%) and newborn meningitic E. coli (NMEC) (60.0%), and absent in all of the 153 intestinal pathogenic E. coli strains tested, thereby validating the designation of the adhesin as ExPEC Adhesin I. In addition, prevalence of EA/I was most frequently associated with the B2 group of the EcoR classification and ST95 complex of the multi locus sequence typing (MLST) scheme, with evidence of a positive selection within this highly pathogenic complex. This is the first report of the newly identified and functionally characterized ExPEC adhesin I and its significant role during APEC infection in chickens
The GimA Locus of Extraintestinal Pathogenic E. coli: Does Reductive Evolution Correlate with Habitat and Pathotype?
IbeA (invasion of brain endothelium), which is located on a genomic island termed GimA, is involved in the pathogenesis of several extraintestinal pathogenic E. coli (ExPEC) pathotypes, including newborn meningitic E. coli (NMEC) and avian pathogenic E. coli (APEC). To unravel the phylogeny of GimA and to investigate its island character, the putative insertion locus of GimA was determined via Long Range PCR and DNA-DNA hybridization in 410 E. coli isolates, including APEC, NMEC, uropathogenic (UPEC), septicemia-associated E. coli (SEPEC), and human and animal fecal isolates as well as in 72 strains of the E. coli reference (ECOR) collection. In addition to a complete GimA (∼20.3 kb) and a locus lacking GimA we found a third pattern containing a 342 bp remnant of GimA in this strain collection. The presence of GimA was almost exclusively detected in strains belonging to phylogenetic group B2. In addition, the complete GimA was significantly more frequent in APEC and NMEC strains while the GimA remnant showed a higher association with UPEC strains. A detailed analysis of the ibeA sequences revealed the phylogeny of this gene to be consistent with that obtained by Multi Locus Sequence Typing of the strains. Although common criteria for genomic islands are partially fulfilled, GimA rather seems to be an ancestral part of phylogenetic group B2, and it would therefore be more appropriate to term this genomic region GimA locus instead of genomic island. The existence of two other patterns reflects a genomic rearrangement in a reductive evolution-like manner
LEAFY COTYLEDON1, FUSCA3 expression and auxin treatment in relation to somatic embryogenesis induction in Arabidopsis
Simultaneous primary infections with Epstein-Barr virus and measles virus in fatal acute encephalitis.
Sequence analysis of measles virus strains collected during the pre- and early-vaccination era in Denmark reveals a considerable diversity of ancient strains
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