Hunger for Culture

The 2016 world premiere of Larissa FastHorse’s play Urban Rez, which Cornerstone Theater Company produced, presented a community-based theater experience in Los Angeles County (Tongva and Tataviam homelands). In this essay, our three co-authors utilize the concept of being a guest on Tongva land as a methodology to demonstrate Two-Spirit, Queer, and Trans representation within Indigenous theater. Through the work of the playwright, cast, and crew, the Urban Rez narrative asserted self-representation in opposition to settler imaginaries through community-based participatory storytelling. Urban Rez represented a pivot in the current American Theater landscape and a continuation of Indigenous theater legacies. Our essay offers a cross-collaboration between three performers from Urban Rez that represent a wide breadth of academic experiences, performance backgrounds, and community organizing to discuss queer, Two-Spirt, and trans experiences. The co-authors discuss the legacy of counter-narratives in Native theater, demonstrate sovereignty in the play, and utilize queer theory to understand an Indigenous queer experience on stage better. We provide a reflexive co-authorship to assert relationality in the face of heteropatriarchy and contend with our hunger for culture. The co-authors recognize the Urban Rez experience as one of the first major Indigenous theater productions in Los Angeles that included queer, Two-Spirit, and transgender characters that rejected justifying representation from a deficit narrative

Susceptibility of Primary HTLV-1 Isolates from Patients with HTLV-1-Associated Myelopathy to Reverse Transcriptase Inhibitors

Since human T-lymphotropic virus type 1 (HTLV-1)-associated diseases are associated with a high HTLV-1 load, reducing this load may treat or prevent disease. However, despite in vitro evidence that certain nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs) are active against HTLV-1, in vivo results have been disappointing. We therefore assayed the sensitivity of HTLV-1 primary isolates to a panel of RT inhibitors. HTLV-1 primary isolates were obtained, pre- and post- NRTI treatment, from patients with HTLV-1-associated myelopathy. Sensitivity to azidothymidine (AZT), lamivudine (3TC), tenofovir (TDF) and three phosphonated carbocyclic 2’-oxa-3’aza nucleosides (PCOANs) was assessed in a RT inhibitor assay. With the exception of 3TC, HTLV RT from primary isolates was less sensitive to all tested inhibitors than HTLV-1 RT from MT-2 cells. HTLV-1 RT from primary isolates and from chronically infected, transformed MT-2 cells was insensitive to 3TC. Sensitivity of primary isolates to RT inhibitors was not reduced following up to 12 months of patient treatment with AZT plus 3TC. The sensitivity of HTLV-1 primary isolates to NRTIs differs from that of cell lines and may vary among patients. Failure of NRTIs to reduce HTLV-1 viral load in vivo was not due to the development of phenotypic NRTI resistance. AZT and the three PCOANs assayed all consistently inhibited primary isolate HTLV-1 RT

Soaking water properties and pea (Pisum sativum) evaluation.

Marrowfat peas are a large seed size pea mainly cultivated in United Kingdom for the production of canned peas which involves the hydration of the seeds by soaking for an extended period of time prior to further processing. Soaking is an important step during legumes production however the property of water used is seldom monitored. This study evaluated the effect of varying soaking water temperature (15 vs. 20 ⁰C) and hardness (soft vs. hard) on hydration kinetics of Marrowfat peas (Pisum sativum). The effect of the pea variety used (Sakura, Kabuki or Maro) has been also considered. Parameters monitored were water hardness, electrical conductivity, turbidity, pH and Brix (%) of the soaking water after 16 hrs. Maximum shear force (texture) of peas. Results have shown that the pea variety had a strong impact on and correlation with the properties assessed, compared to water temperature and harness. Kabuki presented lower turbidity of the soaking water and higher hardness of soaked peas than Sakura and Maro. Furthermore, turbidity was positively correlated with soak ratio. Results have shown that turbidity, a parameter related with leaching of protein and starch during soaking, blanching or cooking, could be a good parameter to monitor during pea soaking in order to have a product with selected properties

Prevalence of antimicrobial resistance and association with patient outcomes in a rural Kenyan hospital

Data on antimicrobial resistance (AMR) and association with outcomes in resource-variable intensive care units (ICU) are lacking. Data currently available are limited to large, urban centers. We attempted to understand this locally through a dual-purpose, retrospective study. Cohort A consisted of adult and pediatric patients who had blood, urine, or cerebrospinal fluid cultures obtained from 2016 to 2020. A total of 3,013 isolates were used to create the Kijabe Hospital’s first antibiogram. Gram-negative organisms were found to be less than 50% susceptible to third- and fourth-generation cephalosporins, 67% susceptible to piperacillin–tazobactam, 87% susceptible to amikacin, and 93% susceptible to meropenem. We then evaluated the association between AMR and clinical characteristics, management, and outcomes among ICU patients (Cohort B). Demographics, vital signs, laboratory results, management data, and outcomes were obtained. Antimicrobial resistance was defined as resistance to one or more antimicrobials. Seventy-six patients were admitted to the ICU with bacteremia during this time. Forty complete paper charts were found for review. Median age was 34 years (interquartile range, 9–51), 26 patients were male (65%), and 28 patients were older than 18 years (70%). Septic shock was the most common diagnosis (n = 22, 55%). Six patients had AMR bacteremia; Escherichia coli was most common (n = 3, 50%). There was not a difference in mortality between patients with AMR versus non-AMR infections (P = 0.54). This study found a prevalence of AMR. There was no association between AMR and outcomes among ICU patients. More studies are needed to understand the impact of AMR in resource-variable settings

Cross-validation of generic risk assessment tools for animal disease incursion based on a case study for African swine fever

In recent years, several generic risk assessment (RA) tools have been developed that can be applied to assess the incursion risk of multiple infectious animal diseases allowing for a rapid response to a variety of newly emerging or re-emerging diseases. Although these tools were originally developed for different purposes, they can be used to answer similar or even identical risk questions. To explore the opportunities for cross-validation, seven generic RA tools were used to assess the incursion risk of African swine fever (ASF) to the Netherlands and Finland for the 2017 situation and for two hypothetical scenarios in which ASF cases were reported in wild boar and/or domestic pigs in Germany. The generic tools ranged from qualitative risk assessment tools to stochastic spatial risk models but were all parameterized using the same global databases for disease occurrence and trade in live animals and animal products. A comparison of absolute results was not possible, because output parameters represented different endpoints, varied from qualitative probability levels to quantitative numbers, and were expressed in different units. Therefore, relative risks across countries and scenarios were calculated for each tool, for the three pathways most in common (trade in live animals, trade in animal products, and wild boar movements) and compared. For the 2017 situation, all tools evaluated the risk to the Netherlands to be higher than Finland for the live animal trade pathway, the risk to Finland the same or higher as the Netherlands for the wild boar pathway, while the tools were inconclusive on the animal products pathway. All tools agreed that the hypothetical presence of ASF in Germany increased the risk to the Netherlands, but not to Finland. The ultimate aim of generic RA tools is to provide risk-based evidence to support risk managers in making informed decisions to mitigate the incursion risk of infectious animal diseases. The case study illustrated that conclusions on the ASF risk were similar across the generic RA tools, despite differences observed in calculated risks. Hence, it was concluded that the cross-validation contributed to the credibility of their results.info:eu-repo/semantics/publishedVersio

Poor CD4+ T Cell Immunogenicity Limits Humoral Immunity to P. falciparum Transmission-Blocking Candidate Pfs25 in Humans.

Plasmodium falciparum transmission-blocking vaccines (TBVs) targeting the Pfs25 antigen have shown promise in mice but the same efficacy has never been achieved in humans. We have previously published pre-clinical data related to a TBV candidate Pfs25-IMX313 encoded in viral vectors which was very promising and hence progressed to human clinical trials. The results from the clinical trial of this vaccine were very modest. Here we unravel why, contrary to mice, this vaccine has failed to induce robust antibody (Ab) titres in humans to elicit transmission-blocking activity. We examined Pfs25-specific B cell and T follicular helper (Tfh) cell responses in mice and humans after vaccination with Pfs25-IMX313 encoded by replication-deficient chimpanzee adenovirus serotype 63 (ChAd63) and the attenuated orthopoxvirus modified vaccinia virus Ankara (MVA) delivered in the heterologous prime-boost regimen via intramuscular route. We found that after vaccination, the Pfs25-IMX313 was immunologically suboptimal in humans compared to mice in terms of serum Ab production and antigen-specific B, CD4+ and Tfh cell responses. We identified that the key determinant for the poor anti-Pfs25 Ab formation in humans was the lack of CD4+ T cell recognition of Pfs25-IMX313 derived peptide epitopes. This is supported by correlations established between the ratio of proliferated antigen-specific CD4+/Tfh-like T cells, CXCL13 sera levels, and the corresponding numbers of circulating Pfs25-specific memory B cells, that consequently reflected on antigen-specific IgG sera levels. These correlations can inform the design of next-generation Pfs25-based vaccines for robust and durable blocking of malaria transmission

Maternal and infant outcomes associated with lithium use in pregnancy

Background Concerns about teratogenicity and offspring complications limit use of lithium in pregnancy. We aimed to investigate the association between in-utero lithium exposure and risk of pregnancy complications, delivery outcomes, neonatal morbidity and congenital malformations. Methods Meta-analysis of primary data analyzed using a shared protocol. Six study sites participated: Denmark, Canada, Netherlands, Sweden, UK, and US, totaling 727 lithium-exposed pregnancies compared to 21,397 reference pregnancies in mothers with a mood disorder, but unexposed to lithium. Main outcome measures included: (1) pregnancy complications, (2) delivery outcomes, (3) neonatal readmission to hospital within 28 days of birth, and (4) congenital malformations (major malformations and cardiac malformations). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were generated using logistic regression models. Site-specific prevalence rates and ORs were pooled using random-effects meta-analytic models. Findings Lithium exposure was not associated with any of the pre-defined pregnancy complications or delivery outcomes. There was an increased risk for neonatal readmission in lithium exposed (27·5%) versus reference group (14·3%) (Pooled aOR1·62; 95% CI: 1·12–2·33). Lithium exposure during first trimester was associated with increased risk of major malformations (7·4% versus 4·3%; pooled aOR 1·71, 95% CI: 1·07–2·72). Similarly, more lithium exposed children had major cardiac malformations, albeit not stasticially significant (2·1% versus 1·6%; pooled aOR 1·54, 95% CI: 0·64–3·70). Limitations in our study include: Serum lithium 5 levels were not available, hence no analyses related to dose-response effects could be performed, and residual confounding from e.g. substance abuse cannot be ruled out. Interpretation Treatment decisions must weigh the potential for increased risks, considering both effct sizes and the precision of the estimates, in particular associated with first-trimester lithium use against its effectiveness at reducing relapse

Combination of RTS,S and Pfs25-IMX313 Induces a Functional Antibody Response Against Malaria Infection and Transmission in Mice

The last two decades saw a dramatic reduction in malaria incidence rates, but this decrease has been stalling recently, indicating control measures are starting to fail. An effective vaccine, particularly one with a marked effect on disease transmission, would undoubtedly be an invaluable tool for efforts to control and eliminate malaria. RTS,S/AS01, the most advanced malaria vaccine to date, targets the parasite before it invades the liver and has the potential to prevent malaria disease as well as transmission by preventing blood stage infection and therefore gametocytogenesis. Unfortunately efficacy in a phase III clinical trial was limited and it is widely believed that a malaria vaccine needed to contain multiple antigens from different life-cycle stages to have a realistic chance of success. A recent study in mice has shown that partially efficacious interventions targeting the pre-erythrocytic and the sexual lifecycle stage synergise in eliminating malaria from a population over multiple generations. Hence, the combination of RTS,S/AS01 with a transmission blocking vaccine (TBV) is highly appealing as a pragmatic and powerful way to increase vaccine efficacy. Here we demonstrate that combining Pfs25-IMX313, one of the TBV candidates currently in clinical development, with RTS,S/AS01 readily induces a functional immune response against both antigens in outbred CD1 mice. Formulation of Pfs25-IMX313 in AS01 significantly increased antibody titres when compared to formulation in Alhydrogel, resulting in improved transmission reducing activity in standard membrane feeding assays (SMFA). Upon co-formulation of Pfs25-IMX313 with RTS,S/AS01, the immunogenicity of both vaccines was maintained, and functional assessment of the induced antibody response by SMFA and inhibition of sporozoite invasion assay (ISI) showed no reduction in biological activity against parasites of both lifecycle stages. Should this findings be translatable to human vaccination this could greatly aid efforts to eliminate and eventually eradicate malaria

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total