Fatal progression of experimental visceral leishmaniasis is associated with intestinal parasitism and secondary infection by commensal bacteria, and is delayed by antibiotic prophylaxis.

Leishmania donovani causes visceral leishmaniasis (VL), which is typically fatal without treatment. There is substantial variation between individuals in rates of disease progression, response to treatment and incidence of post-treatment sequelae, specifically post-kala-azar dermal leishmaniasis (PKDL). Nevertheless, the majority of infected people are asymptomatic carriers. Hamsters and mice are commonly used as models of fatal and non-fatal VL, respectively. Host and parasite genetics are likely to be important factors, but in general the reasons for heterogeneous disease presentation in humans and animal models are poorly understood. Host microbiota has become established as a factor in cutaneous forms of leishmaniasis but this has not been studied in VL. We induced intestinal dysbiosis in mice and hamsters by long-term treatment with broad-spectrum antibiotics in their drinking water. There were no significant differences in disease presentation in dysbiotic mice. In contrast, dysbiotic hamsters infected with L. donovani had delayed onset and progression of weight loss. Half of control hamsters had a rapid progression phenotype compared with none of the ABX-treated animals and the nine-month survival rate was significantly improved compared to untreated controls (40% vs. 10%). Antibiotic-treated hamsters also had significantly less severe hepatosplenomegaly, which was accompanied by a distinct cytokine gene expression profile. The protective effect was not explained by differences in parasite loads or haematological profiles. We further found evidence that the gut-liver axis is a key aspect of fatal VL progression in hamsters, including intestinal parasitism, bacterial translocation to the liver, malakoplakia and iron sequestration, none of which occurred in non-progressing murine VL. Diverse bacterial genera were cultured from VL affected livers, of which Rodentibacter was specifically absent from ABX-treated hamsters, indicating this pathobiont may play a role in promoting disease progression. The results provide experimental support for antibiotic prophylaxis against secondary bacterial infections as an adjunct therapy in human VL patients

Childhood in Sociology and Society: The US Perspective

The field of childhood studies in the US is comprised of cross-disciplinary researchers who theorize and conduct research on both children and youth. US sociologists who study childhood largely draw on the childhood literature published in English. This article focuses on American sociological contributions, but notes relevant contributions from non-American scholars published in English that have shaped and fueled American research. This article also profiles the institutional support of childhood research in the US, specifically outlining the activities of the ‘Children and Youth’ Section of the American Sociological Association (ASA), and assesses the contributions of this area of study for sociology as well as the implications for an interdisciplinary field.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Giving an Account of One’s Pain in the Anthropological Interview

In this paper, I analyze the illness stories narrated by a mother and her 13-year-old son as part of an ethnographic study of child chronic pain sufferers and their families. In examining some of the moral, relational and communicative challenges of giving an account of one’s pain, I focus on what is left out of some accounts of illness and suffering and explore some possible reasons for these elisions. Drawing on recent work by Judith Butler (Giving an Account of Oneself, 2005), I investigate how the pragmatic context of interviews can introduce a form of symbolic violence to narrative accounts. Specifically, I use the term “genre of complaint” to highlight how anthropological research interviews in biomedical settings invoke certain typified forms of suffering that call for the rectification of perceived injustices. Interview narratives articulated in the genre of complaint privilege specific types of pain and suffering and cast others into the background. Giving an account of one’s pain is thus a strategic and selective process, creating interruptions and silences as much as moments of clarity. Therefore, I argue that medical anthropologists ought to attend more closely to the institutional structures and relations that shape the production of illness narratives in interview encounters

Effect of expression level and amino acid sequence on HCMV glycoprotein complexes

Human cytomegalovirus (HCMV) infection is asymptomatic in healthy individuals, but can cause severe disease in immunocompromised people. On the virus envelope, glycoproteins gH/gL form a trimer with gO or a pentamer with UL128-131. These glycoprotein complexes interact with receptors on the host cells to initiate viral fusion and thus are promising sites for vaccine development. The levels of trimer and pentamer significantly influence the infectivity of the virions. Clinical strains of HCMV differ in the relative amounts of trimer and pentamer in the virus particles, however, the mechanism controlling the level of trimer and pentamer is still not clear. My previous research showed that overexpressing UL128-131 results in increased pentamer and decreased trimer levels, suggesting that gO and UL128-131 compete in binding to gH/gL, and that the relative amounts of trimer and pentamer are driven by the expression levels of gO and UL128-131 proteins. The amino acid sequence of gH/gL are highly conserved, whereas gO shows substantial diversity across strains. To elucidate how the diversity of gO affects the formation of trimer and pentamer, we have prepared a library of mutants with gOs from different HCMV strains swapped into one strain, TR. We noted that swapping gO from strain TN into TR results in slow viral replication suggesting incompatibility between gH/gL and gO from different strains. I am conducting an experiment to test whether expressing TNgO in the cell during TR replication will affect the levels of trimer and pentamer as well as the infectivity of the progeny virions. Fibroblasts were infected with TR (with a GFP reporter gene) and subsequently infected with non-replicating adenovirus delivering genes for either TRgO, TNgO, or a control, and analysis is in progress. Progeny virions will be characterized by glycoprotein composition and infectivity using Western blots, qPCR, and flow cytometry

Análisis comparativo de la audiodescripción española y alemana de 'Good-bye, Lenin'

The world\u27s human population has risen exponentially over the last 100 years and is expected to reach nine billion by 2050. Ensuring food security and resource sustainability is of global concern. The United Nations Food and Agriculture Organization endorses insect farming as an alternative to cattle, pork, sheep, and poultry industries because of their higher food conversion rate. Insect farming requires less arable land, less water, and produces less greenhouse gases than traditional livestock. The practice of eating insects, known as entomophagy, is not a new idea as two billion people around the world include insects in their diets. Unfortunately, insects are not typically considered food in the United States, which means health and safety regulations for insect farming, distribution, and consumption are limited, if not nonexistent. There is a need for the redefinition of insects as a legitimate food in the United States through education, media, and policy. To address this need, we have compiled a toolkit for individuals to promote entomophagy in their own communities. The toolkit includes a resolution, food safety regulation templates, two recipe videos, one promotional video on entomophagy in Montana, two educational videos on environmental and nutritional benefits of eating insects, recipes, and a compilation of infographics. Our target audience is environmentally concerned citizens, as they are the most likely group in the country to be early adopters of entomophagy. Interested citizens can use our toolkit to learn about entomophagy, experiment with recipes, host their own insect tasting event, lobby their local governments to adopt a resolution about integrating entomophagy into their climate actions plans, or work with their local health and safety agencies to adopt regulations legitimizing insects as food. We are in final negotiations with the North American Coalition on Insect Agriculture to host our toolkit online in the public domain

Structural retinal changes in cerebral small vessel disease

Cerebral small vessel disease (CSVD) is an important contributor to cognitive impairment and stroke. Previous research has suggested associations with alterations in single retinal layers. We have assessed changes of all individual retinal layers in CSVD using high-resolution optical coherence tomography (OCT) for the first time. Subjects with recent magnetic resonance imaging (MRI) underwent macular and peripapillary retinal imaging using OCT for this case-control study. Number and volume ratio index (WMRI) of white matter lesions (WML) were determined on MRI. Data were analyzed using multiple linear regression models. 27 CSVD patients and 9 control participants were included. Ganglion cell layer (GCL) volume was significantly reduced in patients with CSVD compared to age-matched controls (p = 0.008). In patients with CSVD, larger foveal outer plexiform layer (OPL) volume and decreased temporal peripapillary retinal nerve fiber layer (RNFL) thickness were significantly associated with a higher WMRI in linear regression when controlling for age (p ≤ 0.033). Decreased foveal GCL volume and temporal-inferior RNFL thickness at Bruch's membrane opening (MRW), and increased temporal MRW were associated with a higher WML burden (p ≤ 0.037). Thus, we identified alterations in several OCT layers in individuals with CSVD (GCL, OPL, MRW and RNFL). Their potential diagnostic value merits further study

Experimental bacterial dysbiosis with consequent immune alterations increase intrarectal SIV acquisition susceptibility

Summary: Variations in the composition of the intestinal bacterial microbiome correlate with acquisition of some sexually transmitted pathogens. To experimentally assess the contribution of intestinal dysbiosis to rectal lentiviral acquisition, we induce dysbiosis in rhesus macaques (RMs) with the antibiotic vancomycin prior to repeated low-dose intrarectal challenge with simian immunodeficiency virus (SIV) SIVmac239X. Vancomycin administration reduces T helper 17 (TH17) and TH22 frequencies, increases expression of host bacterial sensors and antibacterial peptides, and increases numbers of transmitted-founder (T/F) variants detected upon SIV acquisition. We observe that SIV acquisition does not correlate with measures of dysbiosis but rather associates with perturbations in the host antimicrobial program. These findings establish a functional association between the intestinal microbiome and susceptibility to lentiviral acquisition across the rectal epithelial barrier

Early cellular mechanisms of type I interferon-driven susceptibility to tuberculosis

Mycobacterium tuberculosis (Mtb) causes 1.6 million deaths annually. Active tuberculosis correlates with a neutrophil-driven type I interferon (IFN) signature, but the cellular mechanisms underlying tuberculosis pathogenesis remain poorly understood. We found that interstitial macrophages (IMs) and plasmacytoid dendritic cells (pDCs) are dominant producers of type I IFN during Mtb infection in mice and non-human primates, and pDCs localize near human Mtb granulomas. Depletion of pDCs reduces Mtb burdens, implicating pDCs in tuberculosis pathogenesis. During IFN-driven disease, we observe abundant DNA-containing neutrophil extracellular traps (NETs) described to activate pDCs. Cell-type-specific disruption of the type I IFN receptor suggests that IFNs act on IMs to inhibit Mtb control. Single-cell RNA sequencing (scRNA-seq) indicates that type I IFN-responsive cells are defective in their response to IFNγ, a cytokine critical for Mtb control. We propose that pDC-derived type I IFNs act on IMs to permit bacterial replication, driving further neutrophil recruitment and active tuberculosis disease

Correction: Mitigation of endemic GI-tract pathogen-mediated inflammation through development of multimodal treatment regimen and its impact on SIV acquisition in rhesus macaques.

[This corrects the article DOI: 10.1371/journal.ppat.1009565.]