Refractory hypoglycaemia in a dog infected with Trypanosoma congolense

A 20 kg German shepherd dog was presented to a French veterinary teaching hospital for seizures and hyperthermia. The dog had returned 1 month previously from a six-month stay in Senegal and sub-Saharan Africa. Biochemistry and haematology showed severe hypoglycaemia (0.12 g/L), anaemia and thrombocytopenia. Despite administration of large amounts of glucose (30 mL of 30% glucose IV and 10 mL of 70% sucrose by gavage tube hourly), 26 consecutive blood glucose measurements were below 0.25 g/L (except one). Routine cytological examination of blood smears revealed numerous free extracytoplasmic protozoa consistent with Trypanosoma congolense. PCR confirmed a Trypanosoma congolense forest-type infection. Treatment consisted of six injections of pentamidine at 48-hour intervals. Trypanosomes had disappeared from the blood smears four days following the first injection. Clinical improvement was correlated with the normalization of laboratory values. The infection relapsed twice and the dog was treated again; clinical signs and parasites disappeared and the dog was considered cured; however, 6 years after this incident, serological examination by ELISA T. congolense was positive. The status of this dog (infected or non-infected) remains unclear. Hypoglycaemia was the most notable clinical feature in this case. It was spectacular in its severity and in its refractory nature; glucose administration seemed only to feed the trypanosomes, indicating that treatment of hypoglycaemia may in fact have been detrimental

Measuring change in inclusion body myositis: clinical assessments versus imaging.

Sporadic inclusion body myositis (sIBM) is a heterogeneous progressive inflammatory muscle disease impacting skeletal muscles in the head, neck, and limbs. Use of valid, reliable, sensitive, and standardised clinical and paraclinical outcome assessments (COA) are critical to inform both proactive clinical care and clinical trial design. Here we review clinical and imaging methods used to quantify muscle strength, size, or function in sIBM, and discuss their application to clinical practice and use in clinical trials. Considerations for future work to validate measures in this population are also discussed

IL-17 Production from T Helper 17, Mucosal-Associated Invariant T, and γδ Cells in Tuberculosis Infection and Disease.

IL-17-producing cells have been shown to be important in the early stages of Mycobacterium tuberculosis (Mtb) infection in animal models. However, there are very little data on the role of IL-17 in human studies of tuberculosis (TB). We recruited TB patients and their highly exposed contacts who were further categorized based on results from an IFN-γ-release assay (IGRA): (1) IGRA positive (IGRA+) at recruitment (latently TB infected), (2) IGRA negative (IGRA-) at recruitment and 6 months [non-converters (NC)], and (3) IGRA- at recruitment and IGRA+ at 6 months (converters). Whole blood was stimulated with mycobacterial antigens and analyzed using T helper (Th) 17 multiplex cytokine assays. Th17, Vγ9Vδ2+, and CD161++Vα7.2+ mucosal-associated invariant T (MAIT) cells were analyzed by flow cytometry. The majority of IL-17 was produced by CD26+CD4+ Th17 cells (median 71%) followed by γδ T cells (6.4%) and MAIT cells (5.8%). TB patients had a significantly lower proportion of Th17 cells and CD4+CD161+Vα7.2+ cells producing both IL-17 and IFN-γ compared to LTBI subjects. IGRA NC had significantly lower levels of CD26-CD4+ and CD8+ MAIT cells producing IL-17 compared to IGRA C but had significantly higher levels of IL-17A, IL-17F, IL-21, and IL-23 in ESAT-6/CFP-10-stimulated supernatants compared to IGRA C. These data provide new insights into the role of IL-17 and IL-17-producing cells at three key stages of the Mtb infection spectrum

Why do staff and family think differently about quality of life in dementia? A qualitative study exploring perspectives in care homes

Background: Quality of life is important especially in incurable illness. In dementia, we often need proxy reports of quality of life, but we know little about how individuals make their judgements. In care homes, proxies may be staff providing care or relatives, but staff rate quality of life differently to family. To our knowledge, no one has explored this qualitatively, so we used qualitative interviews to explore why staff and family think differently about quality of life. Methods: We interviewed 12 staff and 12 relatives who had provided proxy ratings of quality of life for people living with dementia in care homes in the Managing Agitation and Raising Quality of life (MARQUE) study. We asked why they had rated the resident's quality of life as “Very Good, Good, Fair, or Poor.” Using thematic analysis, we compared staff and relatives' proxy responses. Results: For staff, the concept of quality of life was often viewed synonymously with quality of care, influenced by their sense of responsibility and informed by their professional understanding. For relatives, quality of life was often judged in relation to how the person with dementia lived before diagnosis and was influenced by their perception of loss for the person with dementia and their own adjustment. Conclusions: Proxy reports were influenced by rater's own contexts and experiences. This can enhance our understanding of widely used research tools, aid the evaluation of intervention outcomes, and indicate possible targets for improving perceived and actual quality of life of people with dementia

Direct entropy determination and application to artificial spin ice

From thermodynamic origins, the concept of entropy has expanded to a range of statistical measures of uncertainty, which may still be thermodynamically significant. However, laboratory measurements of entropy continue to rely on direct measurements of heat. New technologies that can map out myriads of microscopic degrees of freedom suggest direct determination of configurational entropy by counting in systems where it is thermodynamically inaccessible, such as granular and colloidal materials, proteins and lithographically fabricated nanometre-scale arrays. Here, we demonstrate a conditional-probability technique to calculate entropy densities of translation-invariant states on lattices using limited configuration data on small clusters, and apply it to arrays of interacting nanometre-scale magnetic islands (artificial spin ice). Models for statistically disordered systems can be assessed by applying the method to relative entropy densities. For artificial spin ice, this analysis shows that nearest-neighbour correlations drive longer-range ones.Comment: 10 page

A case of persistent human pegivirus infection in two separate pregnancies of a woman

Human pegivirus (HPgV) is best known for persistent, presumably non-pathogenic, infection and a propensity to co-infect with human immunodeficiency virus or hepatitis C virus. However, unique attributes, such as the increased risk of malignancy or immune modulation, have been recently recognized for HPgV. We have identified a unique case of a woman with high levels HPgV infection in two pregnancies, which occurred 4 years apart and without evidence of human immunodeficiency virus or hepatitis C virus infection. The second pregnancy was complicated by congenital heart disease. A high level of HPgV infection was detected in the maternal blood from different trimesters by RT-PCR and identified as HPgV type 1 genotype 2 in both pregnancies. In the second pregnancy, the decidua and intervillous tissue of the placenta were positive for HPgV by PCR but not the chorion or cord blood (from both pregnancies), suggesting no vertical transmission despite high levels of viremia. The HPgV genome sequence was remarkably conserved over the 4 years. Using VirScan, sera antibodies for HPgV were detected in the first trimester of both pregnancies. We observed the same anti-HPgV antibodies against the non-structural NS5 protein in both pregnancies, suggesting a similar non-E2 protein humoral immune response over time. To the best of our knowledge, this is the first report of persistent HPgV infection involving placental tissues with no clear indication of vertical transmission. Our results reveal a more elaborate viral-host interaction than previously reported, expand our knowledge about tropism, and opens avenues for exploring the replication sites of this virus

Abundance of ACVR1B transcript is elevated during septic conditions: perspectives obtained from a hands-on reductionist investigation

Sepsis is a complex heterogeneous condition, and the current lack of effective risk and outcome predictors hinders the improvement of its management. Using a reductionist approach leveraging publicly available transcriptomic data, we describe a knowledge gap for the role of ACVR1B (activin A receptor type 1B) in sepsis. ACVR1B, a member of the transforming growth factor-beta (TGF-beta) superfamily, was selected based on the following: 1) induction upon in vitro exposure of neutrophils from healthy subjects with the serum of septic patients (GSE49755), and 2) absence or minimal overlap between ACVR1B, sepsis, inflammation, or neutrophil in published literature. Moreover, ACVR1B expression is upregulated in septic melioidosis, a widespread cause of fatal sepsis in the tropics. Key biological concepts extracted from a series of PubMed queries established indirect links between ACVR1B and "cancer", "TGF-beta superfamily", "cell proliferation", "inhibitors of activin", and "apoptosis". We confirmed our observations by measuring ACVR1B transcript abundance in buffy coat samples obtained from healthy individuals (n=3) exposed to septic plasma (n = 26 melioidosis sepsis cases)ex vivo. Based on our re-investigation of publicly available transcriptomic data and newly generated ex vivo data, we provide perspective on the role of ACVR1B during sepsis. Additional experiments for addressing this knowledge gap are discussed

Isolation of Flow and Nonflow Correlations by Two- and Four-Particle Cumulant Measurements of Azimuthal Harmonics in sNN=\sqrt{s_{_{\rm NN}}} = 200 GeV Au+Au Collisions

A data-driven method was applied to measurements of Au+Au collisions at $\sqrt{s_{_{\rm NN}}} =$ 200 GeV made with the STAR detector at RHIC to isolate pseudorapidity distance $\Delta\eta$-dependent and $\Delta\eta$-independent correlations by using two- and four-particle azimuthal cumulant measurements. We identified a component of the correlation that is $\Delta\eta$-independent, which is likely dominated by anisotropic flow and flow fluctuations. It was also found to be independent of $\eta$ within the measured range of pseudorapidity $|\eta|<1$. The relative flow fluctuation was found to be $34\% \pm 2\% (stat.) \pm 3\% (sys.)$ for particles of transverse momentum $p_{T}$ less than $2$ GeV/$c$. The $\Delta\eta$-dependent part may be attributed to nonflow correlations, and is found to be $5\% \pm 2\% (sys.)$ relative to the flow of the measured second harmonic cumulant at $|\Delta\eta| > 0.7$