Natural killer cells in afferent lymph express an activated phenotype and readily produce IFN-γ

Natural killer (NK) cells are motile cells that migrate between peripheral blood (PB), lymph nodes (LNs) and various organs. Domestic animals have frequently been used to study cellular migration, and offer unique opportunities for such studies. The aim of this study was to characterize the phenotype and cytokine producing capacity of NK cells in bovine skin-draining lymph. NKp46/NCR1+ CD3- cells constituted 2-11 % of mononuclear cells in afferent lymph (AL), a majority of cells were CD16+, CD8α+ and CD2-/low, and elevated CD25 and CD44 expression indicated an activated phenotype. Interestingly, significantly fewer AL NK cells expressed the early activation marker CD69 compared to PB NK cells. A large proportion of lymph and blood NK cells produced interferon (IFN)-γ following stimulation with IL-2 and IL-12. Notably, in AL, but not blood, a similar amount of IFN-γ+ NK cells was observed when cells were stimulated with IL-12 alone. Overall, AL NK cells were more similar to LN-residing NK cells than those circulating in PB. We conclude that AL appears to be an important migration route for tissue-activated NK cells, and may represent an alternative route for NK cell traffic to LNs. These findings may have important implications in the development of adjuvant strategies that aim to target NK cells in a vaccine response

Diversity, structure and sources of bacterial communities in earthworm cocoons.

Animals start interactions with the bacteria that will constitute their microbiomes at embryonic stage. After mating, earthworms produce cocoons externally which will be colonized with bacteria from their parents and the environment. Due to the key role bacterial symbionts play on earthworm fitness, it is important to study bacterial colonization during cocoon formation. Here we describe the cocoon microbiome of the earthworms Eisenia andrei and E. fetida, which included 275 and 176 bacterial species, respectively. They were dominated by three vertically-transmitted symbionts, Microbacteriaceae, Verminephrobacter and Ca. Nephrothrix, which accounted for 88% and 66% of the sequences respectively. Verminephrobacter and Ca. Nephrothrix showed a high rate of sequence variation, suggesting that they could be biparentally acquired during mating. The other bacterial species inhabiting the cocoons came from the bedding, where they accounted for a small fraction of the diversity (27% and 7% of bacterial species for E. andrei and E. fetida bedding). Hence, earthworm cocoon microbiome includes a large fraction of the vertically-transmitted symbionts and a minor fraction, but more diverse, horizontally and non-randomly acquired from the environment. These data suggest that horizontally-transmitted bacteria to cocoons may play an important role in the adaptation of earthworms to new environments or diets

Agenda setting and framing of gender-based violence in Nepal: how it became a health issue.

: Gender-based violence (GBV) has been addressed as a policy issue in Nepal since the mid 1990s, yet it was only in 2010 that Nepal developed a legal and policy framework to combat GBV. This article draws on the concepts of agenda setting and framing to analyse the historical processes by which GBV became legitimized as a health policy issue in Nepal and explored factors that facilitated and constrained the opening and closing of windows of opportunity. The results presented are based on a document analysis of the policy and regulatory framework around GBV in Nepal. A content analysis was undertaken. Agenda setting for GBV policies in Nepal evolved over many years and was characterized by the interplay of political context factors, actors and multiple frames. The way the issue was depicted at different times and by different actors played a key role in the delay in bringing health onto the policy agenda. Women's groups and less powerful Ministries developed gender equity and development frames, but it was only when the more powerful human rights frame was promoted by the country's new Constitution and the Office of the Prime Minister that legislation on GBV was achieved and a domestic violence bill was adopted, followed by a National Plan of Action. This eventually enabled the health frame to converge around the development of implementation policies that incorporated health service responses. Our explicit incorporation of framing within the Kindgon model has illustrated how important it is for understanding the emergence of policy issues, and the subsequent debates about their resolution. The framing of a policy problem by certain policy actors, affects the development of each of the three policy streams, and may facilitate or constrain their convergence. The concept of framing therefore lends an additional depth of understanding to the Kindgon agenda setting model.<br/

Pneumatosis intestinalis versus pseudo-pneumatosis: review of CT findings and differentiation

Pneumatosis intestinalis is defined as the presence of gas within the wall of the gastrointestinal tract. Originally described on plain abdominal radiographs, it is an imaging sign rather than a specific diagnosis and it is associated with both benign and life-threatening clinical conditions. The most common life-threatening cause of pneumatosis intestinalis is bowel ischaemia. Computed tomography (CT) is usually requested to detect underlying disease. The presence of pneumatosis intestinalis often leads physicians to make a diagnosis of serious disease. However, an erroneous diagnosis of pneumatosis intestinalis may be made (i.e. pseudo-pneumatosis) when intraluminal beads of gas are trapped within or between faeces and adjacent mucosal folds. The purpose of this pictorial essay is to review and describe the CT imaging findings of pneumatosis and pseudo-pneumatosis intestinalis and to discuss key discriminatory imaging features

Silent cerebral infarct after cardiac catheterization as detected by diffusion weighted Magnetic Resonance Imaging: a randomized comparison of radial and femoral arterial approaches

Background and objective: Cerebral microembolism detected by transcranial Doppler (TCD) occurs systematically during cardiac catheterization, but its clinical relevance, remains unknown. Studies suggest that asymptomatic embolic cerebral infarction detectable by diffusion-weighted (DW) MRI might exist after percutaneous cardiac interventions with a frequency as high as 15 to 22% of cases. We have set up, for the first time, a prospective multicenter trial to assess the rate of silent cerebral infarction after cardiac catheterization and to compare the impact of the arterial access site, comparing radial and femoral access, on this phenomenon. Study design: This prospective study will be performed in patients with severe aortic valve stenosis. To assess the occurrence of cerebral infarction, all patients will undergo cerebral DW-MRI and neurological assessment within 24 hours before, and 48 hours after cardiac catheterization and retrograde catheterization of the aortic valve. Randomization for the access site will be performed before coronary angiography. A subgroup will be monitored by transcranial power M-mode Doppler during cardiac catheterization to observe cerebral blood flow and track emboli. Neuropsychological tests will also be recorded in a subgroup of patients before and after the interventional procedures to assess the impact of silent brain injury on potential cognitive decline. The primary end-point of the study is a direct comparison of ischemic cerebral lesions as detected by serial cerebral DW-MRI between patients explored by radial access and patients explored by femoral access. Secondary end-points include comparison of neuropsychological test performance and number of microembolism signals observed in the two groups. Implications: Using serial DW-MRI, silent cerebral infarction rate will be defined and the potential influence of vascular access site will be evaluated. Silent cerebral infarction might be a major concern during cardiac catheterization and its potential relationship to cognitive decline needs to be assessed. Study registration: The SCIPION study is registered through National Institutes of Health-sponsored clinical trials registry and has been assigned the Identifier: NCT 00329979

Neoadjuvant chemotherapy in the setting of locally advanced olfactory neuroblastoma with intracranial extension

Olfactory neuroblastoma (esthesioneuroblastoma) is a rare malignant tumor of neuroectodermal origin. With only about 1,000 cases reported, there are no clear guidelines regarding management of this disease. Intracranial extension and orbital involvement have been shown to be independent risk factors associated with poorer outcomes. We hereby report a case of a 46-year old male presented with an 8-month history of progressive nasal obstruction and intermittent right-sided epistaxis associated with anosmia and increased pressure sensation in and around the right eye. Further evaluation revealed a large enhancing heterogeneous cystic and solid mass in the right nasal cavity measuring 5.0×5.3×4.6 cm with extension superiorly into the anterior cranial fossa and frontal lobes, ethmoid and sphenoid sinuses. A biopsy of this mass confirmed high grade olfactory neuroblastoma. Because of the intra-cranial extension, a decision was made to start neoadjuvant chemotherapy with cisplatin and etoposide. The patient had very good response to this treatment on a repeat imaging study and went on to have resection of this mass. Post-operatively, he received radiation therapy to the tumor bed and 2 more cycles of chemotherapy. He has been followed now for more than 8 months with no evidence of disease recurrence

Distribution of motor unit potential velocities in short static and prolonged dynamic contractions at low forces: use of the within-subject’s skewness and standard deviation variables

Behaviour of motor unit potential (MUP) velocities in relation to (low) force and duration was investigated in biceps brachii muscle using a surface electrode array. Short static tests of 3.8 s (41 subjects) and prolonged dynamic tests (prolonged tests) of 4 min (30 subjects) were performed as position tasks, applying forces up to 20% of maximal voluntary contraction (MVC). Four variables, derived from the inter-peak latency technique, were used to describe changes in the surface electromyography signal: the mean muscle fibre conduction velocity (CV), the proportion between slow and fast MUPs expressed as the within-subject skewness of MUP velocities, the within-subject standard deviation of MUP velocities [SD-peak velocity (PV)], and the amount of MUPs per second (peak frequency = PF). In short static tests and the initial phase of prolonged tests, larger forces induced an increase of the CV and PF, accompanied with the shift of MUP velocities towards higher values, whereas the SD-PV did not change. During the first 1.5–2 min of the prolonged lower force levels tests (unloaded, and loaded 5 and 10% MVC) the CV and SD-PV slightly decreased and the MUP velocities shifted towards lower values; then the three variables stabilized. The PF values did not change in these tests. However, during the prolonged higher force (20% MVC) test, the CV decreased and MUP velocities shifted towards lower values without stabilization, while the SD-PV broadened and the PF decreased progressively. It is argued that these combined results reflect changes in both neural regulatory strategies and muscle membrane state

Structure of the NheA Component of the Nhe Toxin from Bacillus cereus: Implications for Function

The structure of NheA, a component of the Bacillus cereus Nhe tripartite toxin, has been solved at 2.05 Å resolution using selenomethionine multiple-wavelength anomalous dispersion (MAD). The structure shows it to have a fold that is similar to the Bacillus cereus Hbl-B and E. coli ClyA toxins, and it is therefore a member of the ClyA superfamily of α-helical pore forming toxins (α-PFTs), although its head domain is significantly enlarged compared with those of ClyA or Hbl-B. The hydrophobic β-hairpin structure that is a characteristic of these toxins is replaced by an amphipathic β-hairpin connected to the main structure via a β-latch that is reminiscent of a similar structure in the β-PFT Staphylococcus aureus α-hemolysin. Taken together these results suggest that, although it is a member of an archetypal α-PFT family of toxins, NheA may be capable of forming a β rather than an α pore

Amino Acid Similarity Accounts for T Cell Cross-Reactivity and for “Holes” in the T Cell Repertoire

Background: Cytotoxic T cell (CTL) cross-reactivity is believed to play a pivotal role in generating immune responses but the extent and mechanisms of CTL cross-reactivity remain largely unknown. Several studies suggest that CTL clones can recognize highly diverse peptides, some sharing no obvious sequence identity. The emerging realization in the field is that T cell receptors (TcR) recognize multiple distinct ligands. Principal Findings: First, we analyzed peptide scans of the HIV epitope SLFNTVATL (SFL9) and found that TCR specificity is position dependent and that biochemically similar amino acid substitutions do not drastically affect recognition. Inspired by this, we developed a general model of TCR peptide recognition using amino acid similarity matrices and found that such a model was able to predict the cross-reactivity of a diverse set of CTL epitopes. With this model, we were able to demonstrate that seemingly distinct T cell epitopes, i.e., ones with low sequence identity, are in fact more biochemically similar than expected. Additionally, an analysis of HIV immunogenicity data with our model showed that CTLs have the tendency to respond mostly to peptides that do not resemble self-antigens. Conclusions: T cell cross-reactivity can thus, to an extent greater than earlier appreciated, be explained by amino acid similarity. The results presented in this paper will help resolving some of the long-lasting discussions in the field of T cel

Trabecular bone volume and osteoprotegerin expression in uremic rats given high calcium

Calcium (Ca)-containing phosphate binders have been recommended for the treatment of hyperphosphatemia in children with chronic kidney disease. To study the effects of high Ca levels on trabecular bone volume (BV) and osteoprotegerin (OPG) expression in uremic young rats, a model of marked overcorrection of secondary hyperparathyroidism was created by providing a diet of high Ca to 5/6 nephrectomized young rats (Nx-Ca) for 4 weeks. The results of chondrocyte proliferation and apoptosis, osteoclastic activity, OPG expression and BV were compared among intact rats given the control diet, intact rats given a high Ca diet and 5/6 nephrectomized rats given the control diet (Nx-Control) and the high Ca diet (Nx-Ca). Ionized Ca levels were higher and parathyroid hormone levels were lower in Nx-Ca rats than in the other groups. Final weight, final length and final tibial length of Nx-Ca rats were significantly less than those of the other groups, although the length gain did not differ among the groups. The hypertrophic zone width was markedly enlarged in Nx-Ca rats. Chondrocyte proliferation rates did not differ among the groups, whereas osteoclastic activity was decreased in Nx-Ca rats compared with the Nx-Control animals. The OPG expression and BV were increased in Nx-Ca rats compared with the Nx-Control rats. Increased BV should improve bone strength, whereas disturbance of osteoclastogenesis interferes with bone remodeling. Bone quality has yet to be determined in high Ca-fed uremic young rats