Potential of dietary polyphenols for protection from age-related decline and neurodegeneration: a role for gut microbiota?

Many epidemiological studies have shown the beneficial effects of a largely plant-based diet, and the strong association between the consumption of a Mediterranean-type diet with healthy aging including a lower risk of cognitive decline. The Mediterranean diet is characterized by a high intake of olive oil, fruits and vegetables and is rich in dietary fiber and polyphenols - both of which have been postulated to act as important mediators of these benefits. Polyphenols are large molecules produced by plants to protect them from environmental threats and injury. When ingested by humans, as little as 5% of these molecules are absorbed in the small intestine with the majority metabolized by the gut microbiota into absorbable simple phenolic compounds. Flavan-3-ols, a type of flavonoid, contained in grapes, berries, pome fruits, tea, and cocoa have been associated with many beneficial effects on several risk factors for cardiovascular disease, cognitive function and brain regions involved in memory formation. Both preclinical and clinical studies suggest that these brain and heart benefits can be attributed to endothelial vascular effects and anti-inflammatory properties among others. More recently the gut microbiota has emerged as a potential modulator of the aging brain and intriguingly polyphenols have been shown to alter microbiota composition and be metabolized by different microbial species. However, there is a need for well controlled studies in large populations to identify predictors of response, particularly given the vast inter-individual variation of human gut microbiota.

Determining g_{A}/g_{V} with High-Resolution Spectral Measurements Using a LiInSe_{2} Bolometer.

Neutrinoless double beta decay (0νßß) processes sample a wide range of intermediate forbidden nuclear transitions, which may be impacted by quenching of the axial vector coupling constant (g_{A}/g_{V}), the uncertainty of which plays a pivotal role in determining the sensitivity reach of 0νßß experiments. In this Letter, we present measurements performed on a high-resolution LiInSe_{2} bolometer in a "source=detector" configuration to measure the spectral shape of the fourfold forbidden ß decay of ^{115}In. The value of g_{A}/g_{V} is determined by comparing the spectral shape of theoretical predictions to the experimental ß spectrum taking into account various simulated background components as well as a variety of detector effects. We find evidence of quenching of g_{A}/g_{V} at >5σ with a model-dependent quenching factor of 0.655±0.002 as compared to the free-nucleon value for the interacting shell model. We also measured the ^{115}In half-life to be [5.18±0.06(stat)_{-0.015}^{+0.005}(sys)]×10^{14} yr within the interacting shell model framework. This Letter demonstrates the power of the bolometeric technique to perform precision nuclear physics single-ß decay measurements, which along with improved nuclear modeling can help reduce the uncertainties in the calculation of several decay nuclear matrix elements including those used in 0νßß sensitivity calculations.

Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders.

There is emerging evidence that diet has a major modulatory influence on brain-gut-microbiome (BGM) interactions with important implications for brain health, and for several brain disorders. The BGM system is made up of neuroendocrine, neural, and immune communication channels which establish a network of bidirectional interactions between the brain, the gut and its microbiome. Diet not only plays a crucial role in shaping the gut microbiome, but it can modulate structure and function of the brain through these communication channels. In this review, we summarize the evidence available from preclinical and clinical studies on the influence of dietary habits and interventions on a selected group of psychiatric and neurologic disorders including depression, cognitive decline, Parkinson's disease, autism spectrum disorder and epilepsy. We will particularly address the role of diet-induced microbiome changes which have been implicated in these effects, and some of which are shared between different brain disorders. While the majority of these findings have been demonstrated in preclinical and in cross-sectional, epidemiological studies, to date there is insufficient evidence from mechanistic human studies to make conclusions about causality between a specific diet and microbially mediated brain function. Many of the dietary benefits on microbiome and brain health have been attributed to anti-inflammatory effects mediated by the microbial metabolites of dietary fiber and polyphenols. The new attention given to dietary factors in brain disorders has the potential to improve treatment outcomes with currently available pharmacological and non-pharmacological therapies.

Following excited-state chemical shifts in molecular ultrafast x-ray photoelectron spectroscopy.

The conversion of photon energy into other energetic forms in molecules is accompanied by charge moving on ultrafast timescales. We directly observe the charge motion at a specific site in an electronically excited molecule using time-resolved x-ray photoelectron spectroscopy (TR-XPS). We extend the concept of static chemical shift from conventional XPS by the excited-state chemical shift (ESCS), which is connected to the charge in the framework of a potential model. This allows us to invert TR-XPS spectra to the dynamic charge at a specific atom. We demonstrate the power of TR-XPS by using sulphur 2p-core-electron-emission probing to study the UV-excited dynamics of 2-thiouracil. The method allows us to discover that a major part of the population relaxes to the molecular ground state within 220-250 fs. In addition, a 250-fs oscillation, visible in the kinetic energy of the TR-XPS, reveals a coherent exchange of population among electronic states.

Screening two biodegradable polymers in enhanced efficiency fertiliser formulations reveals the need to prioritise performance goals.

Enhanced efficiency fertilisers (EEF) may reduce nitrogen (N) losses and improve uptake efficiency through synchronising N release with in-season plant requirements. We hypothesised that EEF formed via matrix encapsulation in biodegradable polymers will improve N use efficiency when compared to conventional urea fertiliser. This hypothesis was investigated for two biodegradable polymer matrices: polyhydroxyalkanoate (PHA), containing 11.6% urea (by mass), and polybutylene-adipate-co-terephthalate (PBAT), containing either 19.4 or 32.7% urea; and two contrasting soil types: sand and clay. Nitrogen availability and form was investigated under leaching conditions (water) with a growth accelerator pot experiment involving a horticultural crop and novel non-destructive three-dimensional scanning to measure in-season biomass development. The PBAT 32.7% formulation enabled greater above ground biomass production at both 50 and 100 kg N ha-1 equivalent application rates compared to conventional urea. For the sandy soil, plant scanning indicated that improved uptake performance with PBAT 32.7% was probably the result of greater N availability after 25 days than for conventional urea. Two of the encapsulated formulations (PHA and PBAT 19.4%) tended to decrease nitrogen leaching losses relative to urea (P < 0.05 for the red clay soil). However, decreased N leaching loss was accompanied by poorer N uptake performance, indicative of N being less available in these biopolymer formulations. A snapshot of nitrous oxide emissions collected during peak nitrate concentration (prior to planting and leaching) suggested that the biopolymers promoted N loss via gaseous emission relative to urea in the sandy soil (P < 0.05), and carbon dioxide emissions data suggested that biopolymer-carbon increased microbial activity (P < 0.1). Controlled testing of N release in water was a poor predictor of biomass production and leaching losses. The diverse behaviours of the tested formulations present the potential to optimise biopolymers and their N loadings by taking into account soil and environmental factors that influence the efficient delivery of N to target crops. The greater N uptake efficiency demonstrated for the PBAT 32.7% formulation confirms our hypothesis that matrix encapsulation can enable better synchronisation of N release with crop requirements and decrease leaching losses.

Protein Sorting in Plasmodium Falciparum.

Plasmodium falciparum is a unicellular eukaryote with a very polarized secretory system composed of micronemes rhoptries and dense granules that are required for host cell invasion. P. falciparum, like its relative T. gondii, uses the endolysosomal system to produce the secretory organelles and to ingest host cell proteins. The parasite also has an apicoplast, a secondary endosymbiotic organelle, which depends on vesicular trafficking for appropriate incorporation of nuclear-encoded proteins into the apicoplast. Recently, the central molecules responsible for sorting and trafficking in P. falciparum and T. gondii have been characterized. From these studies, it is now evident that P. falciparum has repurposed the molecules of the endosomal system to the secretory pathway. Additionally, the sorting and vesicular trafficking mechanism seem to be conserved among apicomplexans. This review described the most recent findings on the molecular mechanisms of protein sorting and vesicular trafficking in P. falciparum and revealed that P. falciparum has an amazing secretory machinery that has been cleverly modified to its intracellular lifestyle.

Introduction to effective mentorship for early-career research scientists.

Diversifying the scientific workforce remains a national priority due to the continued lack of representation from underrepresented individuals in STEM fields. Quality mentoring has been identified as a stimulus to enhance not only research success, but also recruitment and retention of underrepresented groups pursuing STEM careers. Utilizing the Entering Mentoring training curriculum framework, this report provides a brief synopsis and key takeaways from the 2019 NIH-ASCB Accomplishing Career Transition (ACT) workshop, "Introduction to Effective Mentorship for Scientists" for 30 senior postdoctoral and early-career faculty researchers from historically underrepresented racial and ethnicity backgrounds. In addition, effective strategies and best practices to enhance STEM mentoring for early-career researchers are provided, which have practical applications for diverse mentoring relationships across disciplines, career stages, and mentee types.

Measuring mineralised tissue formation and resorption in a human 3D osteoblast-osteoclast co-culture model.

In vitro tissue engineered bone constructs have been developed, but models which mimic both formation and resorption in parallel are still lacking. To be used as a model for the bone remodeling process, the formation and resorption of mineralised tissue volume over time needs to be visualised, localised and quantified. The goal of this study was to develop a human 3D osteoblast-osteoclast co-culture in which 1) osteoblasts deposit mineralised matrix, 2) monocytes differentiate into resorbing osteoclasts, and 3) the formation and resorption of mineralised matrix could be quantified over time using micro-computed tomography (µCT). Mesenchymal stromal cells were seeded on silk fibroin scaffolds and differentiated towards osteoblasts to create mineralised constructs. Thereafter, monocytes were added and differentiated towards osteoclasts. The presence of osteoblasts and osteoclasts was confirmed using immunohistochemistry. Osteoclastic activity was confirmed by measuring the increased release of osteoclast marker tartrate resistant acid phosphatase (TRAP), suggesting that osteoclasts were actively resorbing mineralised tissue. Resorption pits were visualised using scanning electron microscopy. Mineralised matrix formation and resorption were quantified using µCT and subsequent scans were registered to visualise remodelling. Both formation and resorption occurred in parallel in the co-culture. The resorbed tissue volume exceeded the formed tissue volume after day 12. In conclusion, the current model was able to visualise, localise and quantify mineralised matrix formation and resorption. Such a model could be used to facilitate fundamental research on bone remodeling, facilitate drug testing and may have clinical implications in personalised medicine by allowing the use of patient cells.

A New Contrast Sensitivity Test for Pediatric Patients: Feasibility and Inter-Examiner Reliability in Ocular Disorders and Cerebral Visual Impairment.

Purpose: Assess feasibility and interexaminer reliability of a new test of contrast sensitivity (CS) for pediatric populations. Methods: The Double Happy (DH) measures CS using a method similar to the Teller Acuity Cards. The schematic DH face is 16 degrees in diameter with features of 0.3 c/d and a channel frequency of 0.8 c/d. DH log10 CS is in 0.15 log unit steps, 0.05 to 2.1. Participants were 43 unselected patients, ages 2 to 18 years: 23 were diagnosed with ocular disorders only; 20 were diagnosed with cerebral visual impairment (CVI). Two examiners measured DH log10 CS. Visual acuity (VA) was also measured. Results: All 43 participants were tested for binocular DH log10CS. Cohen's kappa values for interexaminer reliability were fair. The between examiner ICC was +0.92 (P < 0.001). The mean difference between examiners was near zero, and the 95% CI was -0.44 to 0.45 log10CS. DH log10CS was near normal in the ocular disorder group and reduced in the CVI group. VA was reduced in both groups. DH log10 CS and VA were correlated (r = -0.65). DH log10 CS was a marginally better predictor of diagnosis than VA. Conclusions: DH log10CS test was successful in a diverse pediatric population diagnosed with ocular disorders or CVI. Interexaminer reliability was comparable to that of adults tested previously using the same stimuli and methods. Both CS and VA are reduced in CVI. Translational Relevance: CS and VA both should be tested in pediatric clinical populations, especially in those at risk of CVI.

Is the type of neuraxial anesthesia associated with adverse neonatal outcomes among patients with preeclampsia?

OBJECTIVE: Both preeclampsia and neuraxial anesthesia can alter placental perfusion, potentially affecting the neonatal status. The objective of our study is to quantify the association between type of neuraxial anesthetic and short-term neonatal morbidity among preeclamptic patients undergoing cesarean delivery. METHODS: We performed a secondary analysis of a prospective observational cohort study. Women with singleton gestations and a diagnosis of preeclampsia who underwent cesarean delivery with neuraxial anesthesia were included in the analysis. Short-term neonatal morbidities, defined as neonatal intensive care unit (NICU) admission, arterial cord gas pH ≤7.2 and 5-minute Apgar <7, were compared based on type of neuraxial anesthetic. RESULTS: A total of 4100 patients were included in the analysis, 1696 (41.4%) received spinal anesthesia 1848 (45.1%) received epidural anesthesia and 556 (13.5%) received a combined spinal-epidural (CSE). Antepartum and intrapartum characteristics significantly differed between the groups (p≤0.02). After adjusted analysis, spinal anesthesia was associated with reduced odds of NICU admission, compared with epidural or CSE (OR; 95% CI: 0.79; 0.63-0.98, 0.71; 0.53-0.94, respectively). Spinal anesthesia was also associated with lower odds of a 5-minute Apgar <7 compared with epidural anesthesia (OR 0.59; 95% CI; 0.43-0.83). We found no association between type of anesthesia and arterial cord pH ≤7.2. In stratiifed analysis by gestational age, no association between the type of neuraxial anesthesia and neonatal outcomes was noted among term infants, but associations persisted in preterm infants. CONCLUSIONS: Among women with preeclampsia undergoing cesarean delivery, spinal anesthesia may be associated with reduced short-term neonatal morbidity in preterm infants, compared with epidural or CSE.

Cerebral/Cortical Visual Impairment: A Need to Reassess Current Definitions of Visual Impairment and Blindness.

Cerebral/cortical visual impairment (CVI) is characterized by higher order visual dysfunction caused by injury to the retrogeniculate visual pathways and brain structures which subserve visual processing. CVI has become the leading cause of significant vision loss in children in developed countries, but continues to be an under-recognized cause of visual disability with respect to services aimed at maximizing visual development. Current criteria which are used to define visual disability rely on measures of visual acuity and visual field. Many children who require specialized vision services do not qualify, because these standard definitions of vision impairment do not account for CVI. In order to appropriately identify patients with CVI and offer the resources which may positively impact functional use of vision, the definition of visual impairment and blindness needs to be modified. This commentary calls for a change in the definition of visual impairment and blindness to acknowledge those persons with brain-based vision impairment.

Time of year, age class and body condition predict Hendra virus infection in Australian black flying foxes (Pteropus alecto).

Hendra virus (HeV) continues to cause fatal infection in horses and threaten infection in close-contact humans in eastern Australia. Species of Pteropus bats (flying-foxes) are the natural reservoir of the virus. We caught and sampled flying-foxes from a multispecies roost in southeast Queensland, Australia on eight occasions between June 2013 and June 2014. The effects of sample date, species, sex, age class, body condition score (BCS), pregnancy and lactation on HeV antibody prevalence, log-transformed median fluorescent intensity (lnMFI) values and HeV RNA status were assessed using unbalanced generalised linear models. A total of 1968 flying-foxes were sampled, comprising 1012 Pteropus alecto, 742 P. poliocephalus and 214 P. scapulatus. Sample date, species and age class were each statistically associated with HeV RNA status, antibody status and lnMFI values; BCS was statistically associated with HeV RNA status and antibody status. The findings support immunologically naïve sub-adult P. alecto playing an important role in maintaining HeV infection at a population level. The biological significance of the association between BCS and HeV RNA status, and BCS and HeV antibody status, is less clear and warrants further investigation. Contrary to previous studies, we found no direct association between HeV infection and pregnancy or lactation. The findings in P. poliocephalus suggest that HeV exposure in this species may not result in systemic infection and virus excretion, or alternatively, may reflect assay cross-reactivity with another (unidentified) henipavirus.

Reimagine: a randomized controlled trial of an online, symptom self-management curriculum among breast cancer survivors.

PURPOSE: Chronic pain, depression, and fatigue are common effects resulting from the cancer experience; new interventions are needed. This study examined the effect of Reimagine, an online symptom self-management curriculum that teaches coping skills, on key outcomes. METHODS: Adult breast cancer survivors with chronic pain were recruited from the Army of Women volunteer registry for this randomized controlled trial and randomized 1:1 to Reimagine or usual care conditions. Electronic surveys collected demographic, clinical, and outcome data at baseline and 18 weeks post-intervention. RESULTS: Participants (N = 89) were mean age 56.7 ± 8.7 years; 67% married; 58% employed; mean years since diagnosis 8.2 ± 6.6; and 89% were in remission or cured of their breast cancer. There was a significant difference in the change in depression scores for treatment (M = - 1.7, SD = 4.5) and usual care (M = 0.3, SD = 3.8) conditions; t(85) = - 2.3, p = .03. Difference in the change in fatigue scores was significant for treatment (M = 4.8, SD = 9.0) and usual care (M = 1.2, SD = 6.6) conditions; t(87) = 2.2, p = .03. Most Reimagine users (94%) would recommend the curriculum to others. CONCLUSIONS: These results suggest that Reimagine has an effect on depression and fatigue symptoms for breast cancer survivors. Online programs can be a feasible and effective alternative to in-person support. Additional research is recommended with larger and more diverse samples.

Human erythrocyte band 3 is a host receptor for Plasmodium falciparum glutamic acid-rich protein.

Malaria remains a major global threat to human health and economic development. Microvascular lesions caused by Plasmodium falciparum-infected human erythrocytes/red blood cells are hallmarks of severe pathogenesis contributing to high mortality, particularly in children from sub-Saharan Africa. In this study, we used a phage display complementary DNA library screening strategy to identify P falciparum glutamic acid-rich protein (PfGARP) as a secreted ligand that recognizes an ectodomain of human erythrocyte anion-exchanger, band 3/AE1, as a host receptor. Domain mapping of PfGARP revealed distinct nonoverlapping repeats encoding the immune response epitopes and core erythrocyte-binding activity. Synthetic peptides derived from the erythrocyte-binding repeats of PfGARP induced erythrocyte aggregation reminiscent of the rosetting phenomenon. Using peptides derived from the immunogenic repeats, a quantitative immunoassay was developed to detect a selective immune response against PfGARP in human plasma samples obtained from patients in rural Mali, suggesting the feasibility of PfGARP as a potential biomarker of disease progression. Collectively, our results suggest that PfGARP may play a functional role in enhancing the adhesive properties of human erythrocytes by engaging band 3 as a host receptor. We propose that immunological and pharmacological inhibition of PfGARP may unveil new therapeutic options for mitigating lesions in cerebral and pregnancy-associated malaria.

The surgical management of extra-articular ankylosis in noma patients.

Extraarticular ankylosis occurs frequently in children suffering from noma sequelae. Over 20years of operating on these patients, we observed high recurrence of mouth opening limitation. We therefore progressively changed our surgical strategy. This retrospective study compares the impact of different parameters (types of surgery, noma type, physiotherapy compliance, age and sex) on immediate and long-term mouth opening. It includes a series of 121 patients with extraarticular ankylosis operated on between 1990 and 2015. Soft tissue reconstruction evolved from local and pedicled flaps to large free flaps. Mouth opening was performed by bone-bridge excision, sometimes associated to contralateral coronoidectomy. Mouth opening technique including bilateral coronoidectomy with free flap reconstruction was the only independent factor for significantly better immediate mouth opening with a mean increase of 8.7mm [95% confidence interval (CI) 4.3-13.1, P<0.001) and this effect was maintained in the 3years of follow-up. Another positive factor related to long-term results was excellent physiotherapy, while noma type 4 was a negative factor. Recurrence remains problematic in the management of noma sequelae. If physiotherapy and long-term follow-up cannot be offered, patients should not be operated on, because if limitation of mouth opening recurs, oral feeding may become impossible when a facial defect has been reconstructed.

Local immune response to larvae of Rhipicephalus microplus in Santa Gertrudis cattle.

This study investigated the local immune response at larval attachment sites in Santa Gertrudis cattle with low and high levels of tick resistance. Skin samples with tick larvae attached were collected from Santa Gertrudis cattle at the end of a period of 25 weekly infestations, when the animals manifested highly divergent tick-resistant phenotypes. There was a tendency for more CD3+ , CD4+ , CD8+ , CD25+ , γδ T cells and neutrophils to concentrate at larval tick attachment site in susceptible cattle than in resistant cattle but the differences were significant only for γδ T cells and CD4+ cells. Most of the cattle developed intra-epidermal vesicles at the larval attachment site but the predominant cell within or around the vesicles was the neutrophil in susceptible animals and eosinophil in the resistant animals. The monoclonal antibodies (mAbs) specific for CD45 and CD45 RO antigens reacted with skin leucocytes from a higher number of susceptible cattle than resistant cattle. Our data suggest that some of the cellular responses mounted at larval attachment site are not involved in tick protection. The mAbs specific for CD45 and CD45 RO directly, or a test for CD45 genotype might be developed as markers of tick susceptibility or resistance.

Facile, non-destructive characterization of 2d photonic crystals using UV-vis-spectroscopy.

We present a simple and non-destructive method for characterizing and quantifying the quality of two-dimensional (2D) close-packed arrays of submicron dielectric spheres. Utilizing radiative losses of photonic modes created by the 2D crystals into dielectric substrates we are able to monitor the quality of the particle monolayer during assembly and the size evolution of the individual particles during dry etching. Using an advanced interfacial assembly technique we prepare particle monolayers on glass and characterize the spectral behaviour of the radiative loss regarding different lattice constants, dielectric substrates and layer qualities. The effect of diameter reduction during dry etching is analysed and a simple model is proposed, which enables non-destructive, on spot characterization of the particle layer with sub-20 nm resolution using UV-vis spectroscopy.

Shell-binary nanoparticle materials with variable electrical and electro-mechanical properties.

Nanoparticle (NP) materials with the capability to adjust their electrical and electro-mechanical properties facilitate applications in strain sensing technology. Traditional NP materials based on single component NPs lack a systematic and effective means of tuning their electrical and electro-mechanical properties. Here, we report on a new type of shell-binary NP material fabricated by self-assembly with either homogeneous or heterogeneous arrangements of NPs. Variable electrical and electro-mechanical properties were obtained for both materials. We show that the electrical and electro-mechanical properties of these shell-binary NP materials are highly tunable and strongly affected by the NP species as well as their corresponding volume fraction ratio. The conductivity and the gauge factor of these shell-binary NP materials can be altered by about five and two orders of magnitude, respectively. These shell-binary NP materials with different arrangements of NPs also demonstrate different volume fraction dependent electro-mechanical properties. The shell-binary NP materials with a heterogeneous arrangement of NPs exhibit a peaking of the sensitivity at medium mixing ratios, which arises from the aggregation induced local strain enhancement. Studies on the electron transport regimes and micro-morphologies of these shell-binary NP materials revealed the different mechanisms accounting for the variable electrical and electro-mechanical properties. A model based on effective medium theory is used to describe the electrical and electro-mechanical properties of such shell-binary nanomaterials and shows an excellent match with experiment data. These shell-binary NP materials possess great potential applications in high-performance strain sensing technology due to their variable electrical and electro-mechanical properties.

Surfactants and their role in wound cleansing and biofilm management.

Surfactants are widely used as detergents, emulsifiers, wetting agents, foaming agents and dispersants in the cosmetics, hygiene, food and oil industries. Their use in a clinical setting is also common, particularly within the field of wound care. Many wound cleansers contain surfactants and subsequently there is available data that shows the growing potential of these wound cleansers in the enhancement of wound closure. The presence of microorganisms in wounds has been recognised as a significant factor that delay healing. In complex or chronic wounds that are complicated by biofilms, persistent inflammation or the production of non-viable tissue and slough, the use of surfactants has been shown to aid in the removal of these barriers to wound healing. The use of concentrated surfactant(poloxamer) based wound dressings represent an important component of wound management. Consequently, this article will discuss the effect of clinically used surfactants, with specific focus on a concentrated poloxamer for use against wound biofilm.