IL-17 can be protective or deleterious in murine pneumococcal pneumonia

Streptococcus pneumoniae is the major bacterial cause of community-acquired pneumonia, and the leading agent of childhood pneumonia deaths worldwide. Nasal colonization is an essential step prior to infection. The cytokine IL-17 protects against such colonization and vaccines that enhance IL-17 responses to pneumococcal colonization are being developed. The role of IL-17 in host defence against pneumonia is not known. To address this issue, we have utilized a murine model of pneumococcal pneumonia in which the gene for the IL-17 cytokine family receptor, Il17ra, has been inactivated. Using this model, we show that IL-17 produced predominantly from γδ T cells protects mice against death from the invasive TIGR4 strain (serotype 4) which expresses a relatively thin capsule. However, in pneumonia produced by two heavily encapsulated strains with low invasive potential (serotypes 3 and 6B), IL-17 significantly enhanced mortality. Neutrophil uptake and killing of the serotype 3 strain was significantly impaired compared to the serotype 4 strain and depletion of neutrophils with antibody enhanced survival of mice infected with the highly encapsulated SRL1 strain. These data strongly suggest that IL-17 mediated neutrophil recruitment to the lungs clears infection from the invasive TIGR4 strain but that lung neutrophils exacerbate disease caused by the highly encapsulated pneumococcal strains. Thus, whilst augmenting IL-17 immune responses against pneumococci may decrease nasal colonization, this may worsen outcome during pneumonia caused by some strains

Interleukin-17 is required for control of chronic lung infection caused by Pseudomonas aeruginosa

Chronic pulmonary infection with Pseudomonas aeruginosa is a feature of cystic fibrosis (CF) and other chronic lung diseases. Cytokines of the IL-17 family have been proposed as important in the host response to P. aeruginosa infection through augmenting antibacterial immune responses, although their pro-inflammatory effect may contribute to lung damage that occurs as a result of chronic infection. We set out to explore the role of IL-17 in the host response to chronic P. aeruginosa infection. We used a murine model of chronic pulmonary infection with CF-related strains of P. aeruginosa. We demonstrate that IL-17 cytokine signaling is essential for survival and prevention of chronic infection at 2 weeks post-inoculation using two different P. aeruginosa strains. Following infection, there was a marked expansion of cells within mediastinal lymph nodes, comprised mainly of innate lymphoid cells (ILCs); ∼90% of IL-17 producing cells had markers consistent with Group 3 ILCs. A smaller percentage of IL-17+ cells had markers consistent with a B1 phenotype. In lung homogenates 14 days following infection, there was a significant expansion of IL-17+ cells – about 50% of these were CD3+, split equally between CD4+ Th17 cells and γδ T cells, while the CD3- IL-17+ cells were almost exclusively Group 3 ILCs. Further experiments with B cell deficient mice showed that B cell production of IL-17 or natural antibodies did not provide any defence against chronic P. aeruginosa infection. Thus, IL-17 rather than antibody is a key element in host defence against chronic pulmonary infection with P. aeruginosa

Quantifying, Projecting, and Addressing India's Hidden Hunger

<p>It is estimated that more than two billion people suffer from ‘hidden hunger’ (micronutrient malnutrition) globally, with nearly half living in India. Despite being highlighted as one the most cost-effective investments for human development, progress on addressing micronutrient deficiencies (MiND) has been slowing. The severe social, health, and economic costs of MiND in India should make it a top priority for domestic governance and international donors alike. This study, for the first time, maps food system pathways from crop production through to household-level food availability, for a range of key vitamins, minerals, and amino acids. Results suggest widespread (>80% total Indian population) risk of deficiencies in calcium, vitamin A, B₁₂, folate, in addition to lysine limitation, with more localized deficiencies (<25% population) in iron, zinc, and vitamin B₆. These deficiencies are the result of a combination of a monotonous cereal-dominated diet lacking in diversity, and overall insufficient food intake. This approach also allowed for “MiND by micronutrient” scenario analysis to 2030, to identify potential intervention points in the food system and the capacity of these interventions to address deficiency. Scenario analysis to 2030 and 2050 indicates that, although increased availability of animal-based products, reduction of supply chain losses, and close to maximum (90%) attainable yields could make some contribution to addressing Indian MiND, additional intervention strategies will be essential. Recommendations for intervention in the short (urgent), near-term (2030), and long-term (2050) have been formulated based on this analysis.</p

The Impact of a Multipronged Intervention to Increase School Lunch Participation among Secondary School Students in an Urban Public School District.

Introduction: Schools meals offer a critical opportunity for improving youths' diets, particularly for economically disadvantaged students. We examine the impact of a multipronged intervention to increase middle and high school students' lunch participation in an urban school district. Methods: In school years 2015-2016 through 2017-2018, a quasi-experimental study was conducted in 24 secondary schools, half (n = 12) of which received the following intervention: cafeteria redesign, additional school lunch points-of-sale (mobile carts and vending machines), and teacher education. Results: From baseline to follow-up, lunch participation dropped 4.1% in intervention and 5.1% in comparison schools (difference-in-difference 1.0%, 95% CI 0.5-1.4). The overall decline in lunch participation occurred simultaneously with a drop-in free or reduced-price meal eligibility (from 72% to 58%) across all schools, which is likely related to changing local economic conditions, including a county-wide minimum wage increase that began in summer 2015. Among students eligible for free or reduced-price meals, participation decreased 1.8% in intervention and 4.9% in comparison schools (difference-in-difference 3.1%, 95% CI: 2.5-3.7), with a larger difference-in-difference seen in high schools (5.0%, 95% CI: 4.2-5.9) than middle schools (1.8%, 95% CI: 0.8-2.6). Conclusions: While this intervention demonstrated a modest, but significant relative increase in school lunch participation, the effect was not sufficient to halt large district-wide declines in participation during this study period. Given the significant time, money, and political capital required to implement the intervention, districts should carefully consider similar investments. Broader public policies or other changes to economic conditions that affect eligibility for means-tested benefits-in this case, a strengthening local economy coupled with an increased local minimum wage-may influence school lunch participation more than school-level interventions

Modeling superimposed preeclampsia using Ang II (Angiotensin II) infusion in pregnant stroke-prone spontaneously hypertensive rats

Hypertensive disorders of pregnancy are the second leading cause of maternal deaths worldwide. Superimposed preeclampsia is an increasingly common problem and often associated with impaired placental perfusion. Understanding the underlying mechanisms and developing treatment options are crucial. The pregnant stroke-prone spontaneously hypertensive rat has impaired uteroplacental blood flow and abnormal uterine artery remodeling. We used Ang II (angiotensin II) infusion in pregnant stroke-prone spontaneously hypertensive rats to mimic the increased cardiovascular stress associated with superimposed preeclampsia and examine the impact on the maternal cardiovascular system and fetal development. Continuous infusion of Ang II at 500 or 1000 ng/kg per minute was administered from gestational day 10.5 until term. Radiotelemetry and echocardiography were used to monitor hemodynamic and cardiovascular changes, and urine was collected prepregnancy and throughout gestation. Uterine artery myography assessed uteroplacental vascular function and structure. Fetal measurements were made at gestational day 18.5, and placentas were collected for histological and gene expression analyses. The 1000 ng/kg per minute Ang II treatment significantly increased blood pressure (P&lt;0.01), reduced cardiac output (P&lt;0.05), and reduced diameter and increased stiffness of the uterine arteries (P&lt;0.01) during pregnancy. The albumin:creatinine ratio was increased in both Ang II treatment groups (P&lt;0.05; P&lt;0.0001). The 1000 ng/kg per minute–treated fetuses were significantly smaller than vehicle treatment (P&lt;0.001). Placental expression of Ang II receptors was increased in the junctional zone in 1000 ng/kg per minute Ang II–treated groups (P&lt;0.05), with this zone showing depletion of glycogen content and structural abnormalities. Ang II infusion in pregnant stroke-prone spontaneously hypertensive rats mirrors hemodynamic, cardiac, and urinary profiles observed in preeclamptic women, with evidence of impaired fetal growth

Integrated, portable, tunable, and coherent terahertz sources and sensitive detectors based on layered superconductors

Current compact emitter and receiver technologies are generally inefficient and impractical at terahertz (THz) frequencies between 0.1 and 10 THz. Hence, a gap exists between mature microwave and developed optical technologies. On-chip, integrated broadly tunable and powerful quantum sources that coherently radiate THz waves between 0.1 and 11 THz (potentially extendable to 15 THz) and with potential output power of >1 mW can be achieved based on quantum tunneling of electron pairs across the stack of intrinsic Josephson junctions (IJJs) naturally present in a single crystal of the layered high-Tc superconducting Bi2Sr2CaCu2O8+δ (BSCCO). Such devices have been found to be especially promising solid-state THz sources capable of bridging the entire THz gap, as their wide-frequency tunability range is superior to that obtained from their semiconducting-based rivals, either single resonant-tunneling diodes (RTDs) or THz-quantum cascade lasers (QCLs). Due to the unique electrodynamics of BSCCO, they can also be operated as switching current detectors, paving the way for the realization of on-chip THz-integrated circuits for applications in ultrahigh-speed telecommunications, quantum information, on-chip spectroscopy, and nondestructive sensing, testing, and imaging. This article reviews the history and recent advances in THz sources and detectors based on IJJs with a focus on the application of IJJ THz devices in THz spectroscopy and various types of THz imaging systems such as reflection, transmission, and computed tomography. We show that compact IJJ THz devices with sub-centimeter-sized modules are easy to use in many applications, as they can be regarded as pocket quantum THz torches

Caspase-1 cleavage of the TLR adaptor TRIF inhibits autophagy and β-interferon production during pseudomonas aeruginosa infection

Bacterial infection can trigger autophagy and inflammasome activation, but the effects of inflammasome activation on autophagy are unknown. We examined this in the context of Pseudomonas aeruginosa macrophage infection, which triggers NLRC4 inflammasome activation. P. aeruginosa induced autophagy via TLR4 and its adaptor TRIF. NLRC4 and caspase-1 activation following infection attenuated autophagy. Caspase-1 directly cleaved TRIF to diminish TRIF-mediated signaling, resulting in inhibition of autophagy and in reduced type I interferon production. Expression of a caspase-1 resistant TRIF mutant enhanced autophagy and type I interferon production following infection. Preventing TRIF cleavage by caspase-1 in an in vivo model of P. aeruginosa infection resulted in enhanced bacterial autophagy, attenuated IL-1β production, and increased bacterial clearance. Additionally, TRIF cleavage by caspase-1 diminished NLRP3 inflammasome activation. Thus, caspase-1 mediated TRIF cleavage is a key event in controlling autophagy, type I interferon production, and inflammasome activation with important functional consequences

Millimeter-Wave-to-Terahertz Superconducting Plasmonic Waveguides for Integrated Nanophotonics at Cryogenic Temperatures.

Plasmonics, as a rapidly growing research field, provides new pathways to guide and modulate highly confined light in the microwave-to-optical range of frequencies. We demonstrated a plasmonic slot waveguide, at the nanometer scale, based on the high-transition-temperature (Tc) superconductor Bi2Sr2CaCu2O8+δ (BSCCO), to facilitate the manifestation of chip-scale millimeter wave (mm-wave)-to-terahertz (THz) integrated circuitry operating at cryogenic temperatures. We investigated the effect of geometrical parameters on the modal characteristics of the BSCCO plasmonic slot waveguide between 100 and 800 GHz. In addition, we investigated the thermal sensing of the modal characteristics of the nanoscale superconducting slot waveguide and showed that, at a lower frequency, the fundamental mode of the waveguide had a larger propagation length, a lower effective refractive index, and a strongly localized modal energy. Moreover, we found that our device offered a larger SPP propagation length and higher field confinement than the gold plasmonic waveguides at broad temperature ranges below BSCCO's Tc. The proposed device can provide a new route toward realizing cryogenic low-loss photonic integrated circuitry at the nanoscale

Sand dams as a potential solution to rural water security in drylands: Existing research and future opportunities

Sand dams, a rainwater harvesting technique, are small dams constructed across ephemeral streams. During the rainy season, water is stored in the sand that accumulates behind the dam. Sand dams provide communities in drylands with water during the dry season via scoop holes, pools, and shallow wells. Whilst many studies portray sand dams as a positive solution to the growing threat of dryland water insecurity, others highlight their challenges, including poor water quality, evaporation and leakage from some dams, and the contested failure rate and ability of dams to provide water year-round. This article reviews the peer-reviewed and gray literature on sand dams discovered through Scopus and Google Scholar searches, reference lists, and personal contacts. Findings from the collected literature were reviewed and categorized into sand dam hydrology, health and well-being impacts, economic cost and benefits, and water quality topics. In most numerical simulations, sand dams supply water to the local community throughout much of the dry season and exhibit a long-term positive impact on groundwater. Accounts of water storage and loss based on field measurements, conversely, often show that most water is lost due to evapotranspiration and seepage from the sand reservoir rather than community use. Furthermore, the positive impact on local groundwater storage, while variable, is likely seasonal. Sand dams are relatively affordable to build; construction estimates range from 6,000 to 8,500 EUR. However, existing literature suggests that sand dams are likely not a cost-efficient means of supplying water. Nevertheless, successful sand dams can significantly increase water availability and use, whilst reducing traveling time for water collection, subsequently providing a host of secondary benefits from improved hygiene, economic opportunity, and education. Positive impacts, however, are not equally shared and depend on variables, such as abstraction method, catchment, and household location. Furthermore, their water quality is variable, with high microbiological levels detected especially in scoop holes. Whilst sand dams can increase water security and resilience, they may not be an inclusive solution for all. More research is needed to assess the long-term sustainability of sand dams while accounting for the uncertainty of a changing climate