Intra- or inter-specific difference in genotypes of Caligus elongatus Nordmann 1832?

Two mitochondrial and one nuclear genetic marker were used to study the phylogenetic position of the two reported CO1-genotypes of Caligus elongatus in a group of closely related caligid parasites. Molecular analysis of the two mitochondrial genes (CO1 and 16S), indicate genetic distances of the two C. elongatus genotypes in the lower range of distances previously reported between other crustacean species, but higher than comparable reported within-species differences. Analyses of nuclear 18S sequences indicate no detectable differentiation between these genotypes, but may be due to expected differences in the resolution of these genetic markers. Investigation of two of three selected morphological characters reveals phenotypes supporting the division based on the molecular division. The species status on the two C. elongatus genotypes cannot be drawn conclusively, although the molecular and morphological data presented here suggests the presence of sibling species.     

Involvement of autophagy in MHC class I antigen presentation

MHC class I molecules on the cellular surface display peptides that either derive from endogenous proteins (self or viral), or from endocytosis of molecules, dying cells or pathogens. The conventional antigen-processing pathway for MHC class I presentation depends on proteasome-mediated degradation of the protein followed by transporter associated with antigen-processing (TAP)-mediated transport of the generated peptides into the endoplasmic reticulum (ER). Here, peptides are loaded onto MHC I molecules before transportation to the cell surface. However, several alternative mechanisms have emerged. These include TAP-independent mechanisms, the vacuolar pathway and involvement of autophagy. Autophagy is a cell intrinsic recycling system. It also functions as a defence mechanism that removes pathogens and damaged endocytic compartments from the cytosol. Therefore, it appears likely that autophagy would intersect with the MHC class I presentation pathway to alarm CD8⁺ T cells of an ongoing intracellular infection. However, the importance of autophagy as a source of antigen for presentation on MHC I molecules remains to be defined. Here, original research papers which suggest involvement of autophagy in MHC I antigen presentation are reviewed. The antigens are from herpesvirus, cytomegalovirus and chlamydia. The studies point towards autophagy as important in MHC class I presentation of endogenous proteins during conditions of immune evasion. Because autophagy is a regulated process which is induced upon activation of, for example, pattern recognition receptors (PRRs), it will be crucial to use relevant stimulatory conditions together with primary cells when aiming to confirm the importance of autophagy in MHC class I antigen presentation in future studies.     

The validity of the severity-psychosis hypothesis in depression

BackgroundPsychotic depression (PD) is classified as a subtype of severe depression in the current diagnostic manuals. Accordingly, it is a common conception among psychiatrists that psychotic features in depression arise as a consequence of depressive severity. The aim of this study was to determine whether the severity of depressive and psychotic symptoms correlate in accordance with this “severity–psychosis” hypothesis and to detect potential differences in the clinical features of PD and non-psychotic depression (non-PD).MethodsQuantitative analysis of Health of the Nation Outcome Scales (HoNOS) scores from all patients admitted to a Danish general psychiatric hospital due to a severe depressive episode in the period between 2000 and 2010 was performed.ResultsA total of 357 patients with severe depression, of which 125 (35%) were of the psychotic subtype, formed the study sample. Mean HoNOS scores at admission differed significantly between patients with non-PD and PD on the items hallucinations and delusions (non-PD = 0.33 vs. PD = 1.37, p < 0.001), aggression (non-PD = 0.20 vs. PD = 0.36, p = 0.044) and on the total score (non-PD = 10.55 vs. PD = 11.87, p = 0.024). The HoNOS scores on the two items “depression” and “hallucinations and delusions” were very weakly correlated.LimitationsDiagnoses were based on normal clinical practice and not formalized research criteria.ConclusionsThe symptomatology of PD and non-PD differs beyond the mere psychosis. Furthermore, severity ratings of depressive and psychotic symptoms are very weakly correlated. These findings offer further support to the hypothesis stating that the psychotic- and non-psychotic subtypes of depression may in fact be distinct clinical syndromes.     

Baseline C-reactive protein level as a predictor of mortality in bacteraemia patients: a population-based cohort study

We examined the association between C-reactive protein (CRP) level at time of blood culture (BC) draw and mortality following bacteraemia. Our population-based cohort study comprised all first-time monomicrobial bacteraemia episodes in adults in a Danish county during 1996–2004 (n = 5267). CRP was measured within 24 h of the first positive BC draw. Cox regression was used to compute mortality rate ratios (MRRs) associated with CRP level quartiles (10–64 (reference), 65–143, 144–240 and 241–688 mg/L), controlling for age, gender, comorbidity, specialty, acquisition of infection, and infection focus. We also looked for a biological interaction between CRP level and high magnitude of bacteraemia (three of three culture bottles positive). Thirty-day mortality increased with higher CRP level: adjusted 0–30-day MRRs for patients in the second, third and fourth CRP quartiles were 1.38 (95% CI 1.13–1.69), 1.70 (95% CI 1.40–2.06), and 2.38 (95% CI 1.96–2.87), respectively (p for trend <10⁾⁴). In contrast, mortality associations with CRP during 31–365 days of follow-up were weak (adjusted MRRs for the second to fourth quartiles ranged from 1.18 to 1.28). A high magnitude of bacteraemia strengthened the association between high CRP level and 30-day mortality. We conclude that the CRP level, measured concurrently with the first positive BC, independently predicted 30-day mortality in adult bacteraemia patients.     

13C high-resolution-magic angle spinning MRS reveals differences in glucose metabolism between two breast cancer xenograft models with different gene expression patterns

Tumor cells have increased glycolytic activity, and glucose is mainly used to form lactate and alanine, even when high concentrations of oxygen are present (Warburg effect). The purpose of the present study was to investigate glucose metabolism in two xenograft models representing basal-like and luminal-like breast cancer using (13) C high-resolution-magic angle spinning (HR-MAS) MRS and gene expression analysis. Tumor tissue was collected from two groups for each model: untreated mice (n=19) and a group of mice (n=16) that received an injection of [1-(13) C]-glucose 10 or 15 min before harvesting the tissue. (13) C HR-MAS MRS was performed on the tumor samples and differences in the glucose/alanine (Glc/Ala), glucose/lactate (Glc/Lac) and alanine/lactate (Ala/Lac) ratios between the models were studied. The expression of glycolytic genes was studied using tumor tissue from the same models. In the natural abundance MR spectra, a significantly lower Glc/Ala and Glc/Lac ratio (p<0.001) was observed in the luminal-like model compared with the basal-like model. In the labeled samples, the predominant glucose metabolites were lactate and alanine. Significantly lower Glc/Ala and Glc/Lac ratios were observed in the luminal-like model (p<0.05). Most genes contributing to glycolysis were expressed at higher levels in the luminal-like model (fdr<0.001). The lower Glc/Ala and Glc/Lac ratios and higher glycolytic gene expression observed in the luminal-like model indicates that the transformation of glucose to lactate and alanine occurred faster in this model than in the basal-like model, which has a growth rate several times faster than that of the luminal-like model. The results from the present study suggest that the tumor growth rate is not necessarily a determinant of glycolytic activity.     

Temporal variations in early gut microbial colonization are associated with allergen‐specific immunoglobulin E but not atopic eczema at 2 years of age

Background Intestinal microbiota undergoes substantial development during the first 2 years of life, important for intestinal immunologic development and maturation influencing systemic immune responses. Objective We aimed to investigate, using a prospective study design, whether allergen‐specific IgE (sIgE) and atopic eczema are associated with variations in gut microbial colonization patterns in an unselected population during the first 2 years of life. Methods Faeces from 94 infants were repeatedly sampled from 10 days, 4 months, 1 and 2 years postnatal and analysed for 12 different bacterial species by quantitative real‐time PCR. Venous blood samples from the infants were collected at 2 years of age and were analysed for sIgE for 12 specific allergens. The temporal gut colonization patterns for 42 sIgE‐positive (sIgE?0.35 kU/L) and 52 sIgE‐negative children (sIgE<0.1 kU/L) were then compared. The association between colonization pattern and phenotype as atopic eczema according to UK Working Party (UKWP) criteria were also described. Results Subjects with atopic sensitization had lower levels of Escherichia coli at 4 months and 1 year, higher levels of Bifidobacterium longum at 1 year and lower levels of Bacteroides fragilis at 2 years. For E. coli and B. longum, the differences were only transient and had disappeared by 2 years of age. For other species, there were no differences in colonization patterns, and we found no association between colonization pattern and atopic eczema. Conclusions and Clinical Relevance We found temporal and transient variations in gut microbial colonization patterns associated with differences in sIgE sensitization at 2 years of age. A full understanding of the principles and mechanisms that underlie intestinal microbial colonization and diversity and host–microbiota relationships will be pivotal for the development of therapeutic approaches that manipulate the intestinal microbiota to maintain human health. [Registration number: ISRCTN28090297] Cite this as: O. Storrø, T. Øien, Ø. Langsrud, K. Rudi, C. Dotterud and R. Johnsen, Clinical & Experimental Allergy, 2011 (41) 1545–1554.     

Processes of knowing in the translation of a health communication intervention for dialysis patients awaiting kidney transplantation

ObjectiveTo strengthen patients’ health literacy and their role as active knowledge actors, we developed a health communication intervention including a film-viewing and counselling session for patients awaiting kidney transplantation. We aimed to explore processes of knowing in the translation of the intervention.MethodsWe applied an ethnographic research approach, observing nine intervention sessions with patients and dialysis nurses. Afterwards, the patients and the nurses were interviewed in-depth. Data were analysed using Engebretsen’s modified version of Lonergans’ four-step model of knowing.ResultsThe following knowing processes were identified: i) Knowing as meaning-making; ii) Knowing as acquiring confidence; and iii) Accessing professionals’ and peer experts’ knowledge. Divergent considerations were taken by the different knowledge actors, which had a direct influence on the knowing processes and knowledge translation.ConclusionsThe findings support active interactions between patients and healthcare providers in processes of knowing. These include self-conscious approaches and critical questioning in both parties.Practice implicationsFor transplant professionals, this study demonstrates knowing processes in a real-life context. It also spotlights professional skills and attitudes regarding the importance of self-conscious questioning and a critical interrogating position (for both patients and providers).     

Amplitude of the maximum motor response (Mmax) in human muscles typically decreases during the course of an experiment

 It was shown that the amplitude of the soleus M _max and H _max responses decreases in the course of long-lasting H-reflex studies. The peak-to-peak amplitudes of the M _max and H _max responses in the soleus muscle (and the M _max in the tibialis anterior muscle and small hand muscles) were measured repeatedly for 1–3 h in 20 subjects. 3–5 M _max responses and 5–10 H _max responses were elicited about every 3 min while the subject was at rest. Decreases in the soleus M _max response of up to 50.5% (mean 20.5% SEM 2.2) and of the soleus H _max of up to 49.7% (mean 19.1% SEM 3.7) in relation to the amplitudes measured at the beginning of the experiment were seen in 17 subjects. In 3 subjects no M _max amplitude decrease was seen. The maximum decrease was reached between 10 and 100 min (mean 44.2 min SEM 4.3). An M_max amplitude decrease was also seen in the tibialis anterior muscle and in two small hand muscles. In some subjects the decrease of the M _max response seemed to be initiated by the infrequent supramaximal stimulations. The possible causes for this amplitude reduction, as well as the methodological consequences of these findings for H-reflex studies and fatigue studies, are briefly discussed. Received: 1 July 1998 / Accepted: 9 October 1998     

Results at 10 to 14 years after osteochondral autografting (mosaicplasty) in articular cartilage defects in the knee

PurposeThe aim of this study was to evaluate the medium-term (5–9 years) and long-term (10–14 years) outcomes of mosaicplasty in the knee and identify possible risk factors for poor outcome.MethodsWe included patients 60 years or younger with symptomatic focal full-thickness chondral lesions. Seventy-three patients (87%) with median age of 34 years were available for analyses. Clinical outcome was evaluated by Lysholm score and VAS of pain.ResultsBoth the mean Lysholm score and mean VAS pain score improved significantly from baseline, 49 (SD 17) and 58 (SD 23), respectively, to both the mid-term follow-up, 72 (SD18, p < 0.001) and 27 (SD 20, p < 0.001), respectively, and the long-term follow-up, 72 (SD 21, p < 0.001) and 33 (SD 23, p < 0.001), respectively. A poor outcome at the long-term follow-up – defined as a Lysholm score of 64 or less or having had a knee replacement – was found in 40%. A poor outcome was more frequent in patients 40 years or older (59%), in women (61%) and in defects with an area of 3 cm² or more (57%). Conversely, in a subgroup of male individuals younger than 40 years with defect size less than 3 cm² the failure rate was 12.5% and the mean Lysholm score was 82 (SD 16).ConclusionWe conclude that the long-term clinical outcome after mosaicplasty varies greatly depending on age, gender and the size of the lesion.Level of evidenceIV-Retrospective Case Series.