bluuebunny/crossref_metadata_2025 huggingface dataset:
Terms and nomenclature used for plant-derived components in nutrition and related research: efforts toward harmonization
Authors: Frank Jan , Fukagawa Naomi K , Bilia Anna R , Johnson Elizabeth J , Kwon Oran , Prakash Vish , Miyazawa Teruo , Clifford Michael N , Kay Colin D , Crozier Alan , Erdman John W , Shao Andrew , Williamson Gary
Published: September 2019

Many terms for plant-derived food components are commonly used in the literature, but there is a notable lack of standardization and definition of nomenclature. The use of terms is often field-specific, leading to misunderstanding and problems with literature searches and systematic reviews, and results in isolated and divided research; this impacts not only publication quality but also innovation, regulatory compliance, and enforcement. To begin to address this issue, this narrative review describes the current use and definition of terms. The terms are either chemical and/or origin-based, such as phytochemical (chemicals from plants), or function-based, such as phytonutrient, bioactive, or nutraceutical. The ultimate goal is to establish a common harmonized, evidence-based understanding for when to use each term, thereby providing clarity and a specific scientific basis for such nomenclature. Neither the quality nor the quantity of evidence needed to allow the use of functional terms such as phytonutrient or nutraceutical is specifically discussed here; rather, it is simply noted that evidence is needed to apply these terms. The next step would be to define the evidence necessary for a compound to have a functional descriptor. The aim in this article is to establish scientific criteria for definitions that could be applied to clearly define and differentiate commonly used terms and thus ensure their consistent application in the scientific literature.
Acquiring a Concept of Visual Experience1
Authors: Andrews Austin
Published: September 2019

The transparency of visual experience (transparency) is a widely held and important thesis in the philosophy of perception. Critical discussion of transparency has focused on visual experiences, such as the experience of visual blur that are taken to be counter examples to transparency. Here, I consider a novel objection to transparency that does not depend on intuitions about examples. The objection is that if transparency is true then we cannot explain our ability to think about our visual experiences as such. In response to this objection, I develop an account of how we are able to think about our own visual experiences as such that is compatible with transparency.
A mixture of three engineered phosphotriesterases enables rapid detoxification of the entire spectrum of known threat nerve agents
Authors: Despotović Dragana , Aharon Einav , Dubovetskyi Artem , Leader Haim , Ashani Yacov , Tawfik Dan S
Published: September 2019

Nerve agents are organophosphates (OPs) that potently inhibit acetylcholinesterase, and their enzymatic detoxification has been a long-standing goal. Nerve agents vary widely in size, charge, hydrophobicity and the cleavable ester bond. A single enzyme is therefore unlikely to efficiently hydrolyze all agents. Here, we describe a mixture of three previously developed variants of the bacterial phosphotriesterase (Bd-PTE) that are highly stable and nearly sequence identical. This mixture enables effective detoxification of a broad spectrum of known threat agents—GA (tabun), GB (sarin), GD (soman), GF (cyclosarin), VX and Russian-VX. The potential for dimer dissociation and exchange that could inactivate Bd-PTE has minimal impact, and the three enzyme variants are as active in a mixture as they are individually. To our knowledge, this engineered enzyme ‘cocktail’ comprises the first solution for enzymatic detoxification of the entire range of threat nerve agents.
Between National Polarization and Local Ideology: The Impact of Partisan Competition on State Medicaid Expansion Decisions
Authors: Meyer-Gutbrod Joshua
Published: September 2019

The U.S. Supreme Court’s decision to grant states the authority to reject Medicaid expansion under the Affordable Care Act without penalty threatened the implementation of this polarized health policy. While many Republican-controlled states followed their national allies and rejected Medicaid expansion, others engaged in bipartisan implementation. Why were some Republican states willing to reject the national partisan agenda and cooperate with Democrats in Washington? I focus on the role of electoral competition within states. I conclude that although electoral competition has been shown to encourage partisan polarization within the states, the combination of intergovernmental implementation and Medicaid expansion’s association with public welfare reverses this dynamic. I employ a Cox proportional-hazards model to examine the impact of state partisan ideology and competition on the likelihood of state Medicaid expansion. I find that strong inter-party competition mitigates the impact of more extreme partisan ideologies, encouraging potentially bipartisan negotiation with the federal administration.
To Bubble or Not? A Systematic Review of Bubble Continuous Positive Airway Pressure in Children in Low- and Middle-Income Countries
Authors: Nørgaard Mathilde , Stagstrup Cecilie , Lund Stine , Poulsen Anja
Published: September 2019

Background

Bubble-continuous positive airway pressure (bCPAP) is a simple, low-cost ventilation therapy with the potential to lower morbidity and mortality in children in low- and middle-income countries (LMICs).

Aim

To examine (i) whether bCPAP is a safe and effective treatment for children in all age-groups presenting with respiratory distress from any cause, (ii) LMIC-implemented bCPAP devices including their technical specifications and costs and (iii) the setting and level of health care bCPAP has been implemented in.

Method

A systematic search was performed of Embase, PubMed and Web of Science. Inclusion criteria: bCPAP for children with respiratory distress in all age groups in LMICs. Database searches were performed up to 1 November 2018.

Results

A total of 24 publications were eligible for the review. For neonates bCPAP was superior in improving survival and clinical progression compared with oxygen therapy and mechanical ventilation (MV). In two studies bCPAP was superior to low flow oxygen in reducing mortality in children 29 days to 13 months. Respiratory rate reductions were significant across all ages. Only three of six studies in children of all ages evaluated serious adverse events. In 12 studies comprising 1338 neonates treated with bCPAP, pneumothorax was reported 27 times. The majority of studies were carried out at tertiary hospitals in middle-income countries and 50% implemented the most expensive bCPAP-device.

Conclusion

In neonates and children below 13 months bCPAP is a safe treatment improving clinical outcomes and reducing the need for MV, without an increase in mortality. High-quality studies from non-tertiary settings in low-income countries are needed.
Phyllosphere Colonization by a Soil Streptomyces sp. Promotes Plant Defense Responses Against Fungal Infection
Authors: Vergnes Sophie , Gayrard Damien , Veyssière Marine , Toulotte Justine , Martinez Yves , Dumont Valérie , Bouchez Olivier , Rey Thomas , Dumas Bernard
Published: September 2019

Streptomycetes are soil-dwelling, filamentous actinobacteria and represent a prominent bacterial clade inside the plant root microbiota. The ability of streptomycetes to produce a broad spectrum of antifungal metabolites suggests that these bacteria could be used to manage plant diseases. Here, we describe the identification of a soil Streptomyces strain named AgN23 which strongly activates a large array of defense responses when applied on Arabidopsis thaliana leaves. AgN23 increased the biosynthesis of salicylic acid, leading to the development of salicylic acid induction deficient 2 (SID2)-dependent necrotic lesions. Size exclusion fractionation of plant elicitors secreted by AgN23 showed that these signals are tethered into high molecular weight complexes. AgN23 mycelium was able to colonize the leaf surface, leading to plant resistance against Alternaria brassicicola infection in wild-type Arabidopsis plants. AgN23-induced resistance was found partially compromised in salicylate, jasmonate, and ethylene mutants. Our data show that Streptomyces soil bacteria can develop at the surface of plant leaves to induce defense responses and protection against foliar fungal pathogens, extending their potential use to manage plant diseases.
In-Situ Metabolomic Analysis of Setaria viridis Roots Colonized by Beneficial Endophytic Bacteria
Authors: Agtuca Beverly J. , Stopka Sylwia A. , Tuleski Thalita R. , do Amaral Fernanda P. , Evans Sterling , Liu Yang , Xu Dong , Monteiro Rose Adele , Koppenaal David W. , Paša-Tolić Ljiljana , Anderton Christopher R. , Vertes Akos , Stacey Gary
Published: September 2019

Over the past decades, crop yields have risen in parallel with increasing use of fossil fuel–derived nitrogen (N) fertilizers but with concomitant negative impacts on climate and water resources. There is a need for more sustainable agricultural practices, and biological nitrogen fixation (BNF) could be part of the solution. A variety of nitrogen-fixing, epiphytic, and endophytic plant growth–promoting bacteria (PGPB) are known to stimulate plant growth. However, compared with the rhizobium-legume symbiosis, little mechanistic information is available as to how PGPB affect plant metabolism. Therefore, we investigated the metabolic changes in roots of the model grass species Setaria viridis upon endophytic colonization by Herbaspirillum seropedicae SmR1 (fix+) or a fix− mutant strain (SmR54) compared with uninoculated roots. Endophytic colonization of the root is highly localized and, hence, analysis of whole-root segments dilutes the metabolic signature of those few cells impacted by the bacteria. Therefore, we utilized in-situ laser ablation electrospray ionization mass spectrometry to sample only those root segments at or adjacent to the sites of bacterial colonization. Metabolites involved in purine, zeatin, and riboflavin pathways were significantly more abundant in inoculated plants, while metabolites indicative of nitrogen, starch, and sucrose metabolism were reduced in roots inoculated with the fix− strain or uninoculated, presumably due to N limitation. Interestingly, compounds, involved in indole-alkaloid biosynthesis were more abundant in the roots colonized by the fix− strain, perhaps reflecting a plant defense response.
Revisiting Sustainability of Fungicide Seed Treatments for Field Crops
Authors: Lamichhane Jay Ram , You Ming Pei , Laudinot Véronique , Barbetti Martin J. , Aubertot Jean-Noël
Published: September 2019

The use of fungicide seed treatment (FST) is a very common practice worldwide. The purported effectiveness of many fungicides in providing broad-spectrum and systemic control of important diseases and the perception that FST reduces overall pesticide use, hence lowering environmental impacts, have greatly promoted the use of FST in the last five decades. Since there have been rapid advancements in the types, formulations, and application methods for seed treatments, there is a need to re-evaluate the benefits versus the risks of FST as a practice. While the use of seeds treated with neonicotinoid insecticides has come under scrutiny due to concern over potential nontarget effects, there are knowledge gaps on potential negative impacts of FST on operators’ (those who apply, handle, and use treated seeds) health and nontarget soil organisms (both macro- and microorganisms). Here we review existing knowledge on key fungicides used for seed treatments, benefits and risks related to FST, and propose recommendations to increase benefits and limit risks related to the use of FST. We found FST is applied to almost 100% of sown seeds for the most important arable crops worldwide. Fungicides belonging to 10 chemical families and with one or several types of mobility (contact, locally systemic, and xylem mobile) are used for seed treatment, although the majority are xylem mobile. Seed treatments are applied by the seed distributor, the seed company, and the farmer, although the proportion of seed lots treated by these three groups vary from one crop to another. The average quantity of fungicide active ingredient (a.i.) applied via seed treatment depends on the crop species, environment(s) into which seed is planted, and regional or local regulations. Cost-effectiveness, protection of the seed and seedlings from pathogens up to 4–5 weeks from sowing, user friendliness, and lower impact on human health and nontarget soil organisms compared with foliar spray and broadcast application techniques, are among the most claimed benefits attributed to FST. In contrast, inconsistent economic benefits, development of resistance by soilborne pathogens to many fungicides, exposure risks to operators, and negative impacts on nontarget soil organisms are the key identified risks related to FST. We propose eight recommendations to reduce risks related to FST and to increase their benefits.
Endomucin restores depleted endothelial glycocalyx in the retinas of streptozotocin‐induced diabetic rats
Authors: Niu Tian , Zhao Mengya , Jiang Yan , Xing Xindan , Shi Xin , Cheng Lu , Jin Huiyi , Liu Kun
Published: September 2019

Endothelial glycocalyx plays a significant role in the development and progression of diabetic complications. Endomucin (EMCN) is an anti‐inflammatory membrane glycoprotein that is mainly expressed in venous and capillary endothelial cells. However, the function of EMCN in diabetic retinopathy (DR) progression is still completely unknown. We first investigated the change of EMCN expression in the retina and human retinal microvascular endothelial cells. We then overexpressed EMCN in the retina with adeno‐associated virus and induced DR with streptozotocin (STZ). We analyzed EMCN's effect on the integrity of endothelial glycocalyx under conditions of DR. Furthermore, we investigated EMCN's protective effect against inflammation and blood‐retinal barrier (BRB) destruction. We found that EMCN is specifically expressed in retinal endothelial cells and that its levels are decreased during hyperglycemia in vitro and in vivo. Overexpression of EMCN can restore the retinal endothelial glycocalyx of STZ‐induced diabetic rats. Furthermore, EMCN overexpression can decrease leukocyte‐endothelial adhesion to ameliorate inflammation and stabilize the BRB to inhibit vessel leakage in rats with DR. EMCN may protect patients with diabetes from retinal vascular degeneration by restoring the endothelial glycocalyx. EMCN may thus represent a novel therapeutic strategy for DR because it targets endothelial glycocalyx degradation associated with this disease.—Niu, T., Zhao, M., Jiang, Y., Xing, X., Shi, X., Cheng, L., Jin, H., Liu, K. Endomucin restores depleted endothelial glycocalyx in the retinas of streptozotocin‐induced diabetic rats. FASEB J. 33, 13346–13357 (2019). www.fasebj.org
Extracellular RNAs in periodontopathogenic outer membrane vesicles promote TNF‐α production in human macrophages and cross the blood‐brain barrier in mice
Authors: Han Eun‐Chong , Choi Song‐Yi , Lee Youngkyun , Park Jin‐Woo , Hong Su‐Hyung , Lee Heon‐Jin
Published: September 2019

Among the main bacteria implicated in the pathology of periodontal disease, Aggregatibacter actinomycetemcomitans (Aa) is well known for causing loss of periodontal attachment and systemic disease. Recent studies have suggested that secreted extracellular RNAs (exRNAs) from several bacteria may be important in periodontitis, although their role is unclear. Emerging evidence indicates that exRNAs circulate in nanosized bilayered and membranous extracellular vesicles (EVs) known as outer membrane vesicles (OMVs) in gram‐negative bacteria. In this study, we analyzed the small RNA expression profiles in activated human macrophage‐like cells (U937) infected with OMVs from Aa and investigated whether these cells can harbor exRNAs of bacterial origin that have been loaded into the host RNA‐induced silencing complex, thus regulating host target transcripts. Our results provide evidence for the cytoplasmic delivery and activity of microbial EV‐derived small exRNAs in host gene regulation. The production of TNF‐α was promoted by exRNAs via the TLR‐8 and NF‐κB signaling pathways. Numerous studies have linked periodontal disease to neuroinflammatory diseases but without elucidating specific mechanisms for the connection. We show here that intracardiac injection of Aa OMVs in mice showed successful delivery to the brain after crossing the blood‐brain barrier, the exRNA cargos increasing expression of TNF‐α in the mouse brain. The current study indicates that host gene regulation by microRNAs originating from OMVs of the periodontal pathogen Aa is a novel mechanism for host gene regulation and that the transfer of OMV exRNAs to the brain may cause neuroinflammatory diseases like Alzheimer's.—Han, E.‐C., Choi, S.‐Y., Lee, Y., Park, J.‐W., Hong S.‐H., Lee, H.‐J. Extracellular RNAs in periodontopathogenic outer membrane vesicles promote TNF‐α production in human macrophages and cross the blood‐brain barrier in mice. FASEB J. 33, 13412–13422 (2019). www.fasebj.org
Persistence of pain in humans and other mammals
Authors: Williams Amanda C. de C.
Published: September 2019

Evolutionary models of chronic pain are relatively undeveloped, but mainly concern dysregulation of an efficient acute defence, or false alarm. Here, a third possibility, mismatch with the modern environment, is examined. In ancestral human and free-living animal environments, survival needs urge a return to activity during recovery, despite pain, but modern environments allow humans and domesticated animals prolonged inactivity after injury. This review uses the research literature to compare humans and other mammals, who share pain neurophysiology, on risk factors for pain persistence, behaviours associated with pain, and responses of conspecifics to behaviours. The mammal populations studied are mainly laboratory rodents in pain research, and farm and companion animals in veterinary research, with observations of captive and free-living primates. Beyond farm animals and rodent models, there is virtually no evidence of chronic pain in other mammals. Since evidence is sparse, it is hard to conclude that it does not occur, but its apparent absence is compatible with the mismatch hypothesis.

This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Listening to your gut: immune challenge to the gut sensitizes body wall nociception in the caterpillarManduca sexta
Authors: Adamo Shelley A. , McMillan Laura E.
Published: September 2019

Immune–nociceptor connections are found in animals across phyla. Local inflammation and/or damage results in increased nociceptive sensitivity of the affected area. However, in mammals, immune responses far from peripheral nociceptors, such as immune responses in the gut, produce a general increase in peripheral nociceptive sensitivity. This phenomenon has not, to our knowledge, been found in other animal groups. We found that consuming heat-killed pathogens reduced the tactile force needed to induce a defensive strike in the caterpillarManduca sexta. This increase in the nociceptive sensitivity of the body wall is probably part of the reconfiguration of behaviour and physiology that occurs during an immune response (e.g. sickness behaviour). This increase may help enhance anti-predator behaviour as molecular resources are shifted towards the immune system.

This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Early-life injury produces lifelong neural hyperexcitability, cognitive deficit and altered defensive behaviour in the squidEuprymna scolopes
Authors: Howard Ryan B. , Lopes Lauren N. , Lardie Christina R. , Perez Paul P. , Crook Robyn J.
Published: September 2019

Injury occurring in the neonatal period in mammals is known to induce plasticity in pain pathways that may lead to pain dysfunction in later life. Whether these effects are unique to the mammalian nervous system is not well understood. Here, we investigate whether similar effects of early-life injury are found in a large-brained comparative model, the cephalopodEuprymna scolopes. We show that the peripheral nervous system ofE. scolopesundergoes profound and permanent plasticity after injury of peripheral tissue in the early post-hatching period, but not after the same injury given in the later juvenile period. Additionally, both innate defensive behaviour and learning are impaired by injury in early life. We suggest that these similar patterns of nervous system and behavioural remodelling that occur in squid and in mammals indicate an adaptive value for long-lasting plasticity arising from early-life injury, and suggest that injuries inflicted in very early life may signal to the nervous system that the environment is highly dangerous. Thus, neonatal pain plasticity may be a conserved pattern whose purpose is to set the developing nervous system's baseline responsiveness to threat.

This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
The facial expression of pain in humans considered from a social perspective
Authors: Kappesser Judith
Published: September 2019

The social modulation of pain in humans has been neglected so far with respect to verbal as well as non-verbal communication of pain. The facial pain expression is a powerful way to communicate pain, and there are some theoretical accounts available on how social modulation may affect the encoding of the facial expression of pain. Some accounts, particularly in the pain field, are proximate explanations on the mechanisms involved, whereas an evolutionary psychology account takes a more comprehensive approach. A review of nine experimental studies revealed that in the majority of studies (6/9), social context had an effect on the facial pain expression, but results were inconsistent. Several conceptual and methodological issues are discussed which may explain these inconsistencies and could help in design of future experimental studies.

This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
The translatability of pain across species
Authors: Mogil Jeffrey S.
Published: September 2019

The poor translational record of pain research has suggested to some observers that species differences in pain biology might be to blame. In this review, I consider the evidence for species similarity and differences in the pain research literature. Impressive feats of translation have been demonstrated in relation to certain genetic effects, social modulation of pain and pain memory. The degree to which pain biology in rodents predicts pain biology in humans has important implications both for evolutionary accounts of pain, but also the success of analgesic drug development going forward.

This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Peripheralstraightjacket(α2δ Ca2+channel subunit) expression is required for neuropathic sensitization inDrosophila
Authors: Khuong Thang M. , Hamoudi Zina , Manion John , Loo Lipin , Muralidharan Arjun , Neely G. Gregory
Published: September 2019

Nerve injury leads to devastating and often untreatable neuropathic pain. While acute noxious sensation (nociception) is a crucial survival mechanism and is conserved across phyla, chronic neuropathic pain is considered a maladaptive response owing to its devastating impact on a patient's quality of life. We have recently shown that a neuropathic pain-like response occurs in adultDrosophila. However, the mechanisms underlying this phenomenon are largely unknown. Previous studies have shown that the α2δ peripheral calcium channel subunitstraightjacket(stj) is a conserved factor required for thermal pain perception. We demonstrate here thatstjis required in peripheralppk+sensory neurons for acute thermal responses and that it mediates nociceptive hypersensitivity in an adultDrosophilamodel of neuropathic pain-like disease. Given that calcium channels are the main targets of gabapentinoids (pregabalin and gabapentin), we assessed if these drugs can alleviate nociceptive hypersensitivity. Our findings suggest that gabapentinoids may prevent nociceptive hypersensitivity by preserving central inhibition after nerve injury. Together, our data further highlight the similarity of some mechanisms for pain-like conditions acrossphylaand validates the scientific use ofDrosophilaneuropathic sensitization models for analgesic drug discovery.

This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Evolution of nociception and pain: evidence from fish models
Authors: Sneddon Lynne U.
Published: September 2019

In order to survive, animals must avoid injury and be able to detect potentially damaging stimuli via nociceptive mechanisms. If the injury is accompanied by a negative affective component, future behaviour should be altered and one can conclude the animal experienced the discomfort associated with pain. Fishes are the most successful vertebrate group when considering the number of species that have filled a variety of aquatic niches. The empirical evidence for nociception in fishes from the underlying molecular biology, neurobiology and anatomy of nociceptors through to whole animal behavioural responses is reviewed to demonstrate the evolutionary conservation of nociception and pain from invertebrates to vertebrates. Studies in fish have shown that the biology of the nociceptive system is strikingly similar to that found in mammals. Further, potentially painful events result in behavioural and physiological changes such as reduced activity, guarding behaviour, suspension of normal behaviour, increased ventilation rate and abnormal behaviours which are all prevented by the use of pain-relieving drugs. Fish also perform competing tasks less well when treated with a putative painful stimulus. Therefore, there is ample evidence to demonstrate that it is highly likely that fish experience pain and that pain-related behavioural changes are conserved across vertebrates.

This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Evolution of acid nociception: ion channels and receptors for detecting acid
Authors: Pattison Luke A. , Callejo Gerard , St John Smith Ewan
Published: September 2019

Nociceptors, i.e. sensory neurons tuned to detect noxious stimuli, are found in numerous phyla of the Animalia kingdom and are often polymodal, responding to a variety of stimuli, e.g. heat, cold, pressure and chemicals, such as acid. Owing to the ability of protons to have a profound effect on ionic homeostasis and damage macromolecular structures, it is no wonder that the ability to detect acid is conserved across many species. To detect changes in pH, nociceptors are equipped with an assortment of different acid sensors, some of which can detect mild changes in pH, such as the acid-sensing ion channels, proton-sensing G protein-coupled receptors and several two-pore potassium channels, whereas others, such as the transient receptor potential vanilloid 1 ion channel, require larger shifts in pH. This review will discuss the evolution of acid sensation and the different mechanisms by which nociceptors can detect acid.

This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Discrimination between nociceptive reflexes and more complex responses consistent with pain in crustaceans
Authors: Elwood Robert W.
Published: September 2019

Animals have quick-acting nociceptive reflexes that protect them from tissue damage. Some taxa have also evolved the capacity for pain. Pain appears to be linked to long-term changes in motivation brought about by the aversive nature of the experience. Pain presumably enhances long-term protection through behaviour modification based, in part, on memory. However, crustaceans have long been viewed as responding purely by reflex and thus not experiencing pain. This paper considers behavioural and physiological criteria that distinguish nociception from potential pain in this taxon. These include trade-offs with other motivational systems and prolonged motivational change. Complex, prolonged grooming or rubbing demonstrate the perception of the specific site of stimulus application. Recent evidence of fitness-enhancing, anxiety-like states is also consistent with the idea of pain. Physiological changes in response to noxious stimuli mediate some of the behavioural change. Rapid avoidance learning and prolonged memory indicate central processing rather than mere reflexes. Thus, available data go beyond the idea of just nociception. However, the impossibility of total proof of pain described in ways appropriate for our own species means that pain in crustaceans is still disputed. Pain in animals should be defined in ways that do not depend on human pain experience.

This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Self-reported Morisky 8 item medication adherence scale to statins concords with pill count method and correlates with serum lipid profile parameters and Serum HMGCoA Reductase levels
Authors: Grover Abhinav , Oberoi Mansi , Rehan Harmeet , Gupta Lalit , Yadav Madhur
Published: September 2019

Background

It is imperative that non-compliance to statins be identified and addressed to optimize the clinical benefit of statins. Patient self-reporting methods are convenient to apply in clinical practice but need to be validated.

Objective

We studied the concordance of a patient self-report method, MMAS (Morisky eight item medication adherence scale) with pill count method in measuring adherence to statins and their correlation with extended lipid profile parameters and serum HMGCoA-R (hydroxymethylglutaryl coenzyme A reductase) enzyme levels.

Methods

MMAS and pill count method were used to measure the adherence to statins in patients on statins for any duration. Patients were subjected to estimation of extended lipid profile and serum HMGCoA-R levels at the end of 3 months follow-up.

Results

Out of a total of 200 patients included in the study, 117 patients had low adherence (score less than 6 on MMAS) whereas 65 and 18 patients had medium (score 6 to less than 8) and high adherence (score of 8) respectively. Majority of patients who had low adherence to statins by MMAS were nonadherent by pill count method yielding concordance of 96.5%. Medium or high adherence to statins by MMAS method had concordance of 89.1% with pill count method. The levels of total cholesterol, low density lipoprotein-cholesterol, apolipoprotein B and HMGCoA-R were significantly negatively correlated with compliance measured by pill count and MMAS with similar correlation coefficients. HMGCoA-R levels demonstrated a plateau phenomenon with levels being 9-10 ng/ml when compliance to statin therapy was greater than 60% by pill count and greater than 6 on Morisky scale.

Conclusion

In conclusion, MMAS and pill count methods showed concordance in measuring adherence to statins. These methods need to be explored further for their interchangeability as surrogates for biomarker levels.
A mosquito survey along a transect of urbanization in Dschang, West Region of Cameroon, reveals potential risk of arbovirus spillovers
Authors: Audrey Mayi Marie Paul , Roland Bamou , Borel Djiappi-Tchamen , Carelle Djojo-Tachegoum , Albin Fontaine , Christophe Antonio-Nkondjio , Timoleon Tchuinkam
Published: September 2019

Background

With the advance of globalization and the decline of wild habitats, mosquito-borne viruses are no longer confined to their original sylvatic environments and are emerging or remerging worldwide. However, little is known about the mosquito species implicated in the spillovers of these viruses from their enzootic cycles.

Method

We conducted an entomological field survey to catalogue the relative abundance of the Culicidae fauna in rural, peri-urban and urban areas in the Dschang locality in West Cameroon. Mosquitoes were collected from March-April and July-August 2019 at both aquatic and adult stages, and identified using stereomicroscopes and morphological identification keys.

Results

A total of 1,401 mosquitoes belonging to 4 genera and 26 species were collected (n=427, 470 and 504 in rural, peri-urban and urban areas respectively). The most abundant species Aedes africanus (45.47%) as well as Culex moucheti (8.92 %) were encountered in peri-urban and rural environments. Species like Culex duttoni (14.49%), Culex quinquefasciatus (2.35%) and Aedes aegypti (1.36%) were solely found in urban area. Aedes albopictus (14.42%), Culex (Culiciomyia) (6.57%), Culex tigripes (1.43%) and Eretmapodites chrysogaster (0.64%) on the other hand were collected in the three study sites. Importantly, all these species have been suspected or incriminated as vectors of many arboviruses.

Conclusion

This study identified potential sylvatic, urban and bridge-vectors that can play a role in current or future virus emergence in Cameroon. Further investigations are needed to assess if arboviruses are circulating in these areas and to study the vector role of each mosquito species in arbovirus transmission.
Differential Nr4a1 and Nr4a3 expression discriminates tonic from activated TCR signalling events in vivo
Authors: Jennings Emma , Elliot Thomas A.E. , Thawait Natasha , Kanabar Shivani , Yam-Puc Juan Carlos , Ono Masahiro , Toellner Kai-Michael , Wraith David C. , Anderson Graham , Bending David
Published: September 2019

Nr4areceptors are activated by T cell receptor (TCR) and B cell receptor (BCR) signalling and play key roles in T cell differentiation and promoting T cell exhaustion. How TCR signalling pathways regulate Nr4a receptors and their sensitivities to different physiological types of TCR signalling (e.g. tonic versus activating) remains unknown. Here we utilise Nr4a1/Nur77-GFP andNr4a3-Tocky mice to elucidate the signalling pathways that govern Nr4a receptor expression in CD4+and CD8+T cells. Our findings reveal thatNr4a1-3are Src family kinase-dependent. Moreover,Nr4a2andNr4a3are abolished by calcineurin inhibitors and bind NFAT1, highlighting a necessary and sufficient role for NFAT in the control ofNr4a2andNr4a3, but redundancy for NFAT forNr4a1. During T cell development, Nr4a1 is activated by tonic signalling during TCR-beta selection in the thymus, whilst Nr4a3 requires cognate peptide:MHC interactions for expression. Thus, due to differential sensitivity of Nr4a1 and Nr4a3 to TCR signalling pathways, T cells undergoing tonic versus activating TCR signalling events can be distinguished in vivo.
Inertial sensor-based centripetal acceleration as a correlate for lateral margin of stability during walking and turning
Authors: Fino Peter C. , Horak Fay B. , Curtze Carolin
Published: September 2019

There is growing interest in using inertial sensors to continuously monitor gait during free-living mobility. Inertial sensors can provide many gait measures, but they struggle to capture the spatial stability of the center-of-mass due to limitations estimating sensor-to-sensor distance. While the margin of stability (MoS) is an established outcome describing the instantaneous mechanical stability of gait relating to fall-risk, methods to estimate the MoS from inertial sensors have been lacking. Here, we developed and tested a framework, based on centripetal acceleration, to determine a correlate for the lateral MoS using inertial sensors during walking with or without turning. Using three synchronized sensors located bilaterally on the feet and lumbar spine, the average centripetal acceleration over the subsequent step can be used as a correlate for lateral MoS. Relying only on a single sensor on the lumbar spine yielded similar results if the stance foot can be determined from other means. Additionally, the centripetal acceleration correlate of lateral MoS demonstrates clear differences between walking and turning, inside and outside turning limbs, and speed. While limitations and assumptions need to be considered when implemented in practice, this method presents a novel correlate for the lateral MoS during walking and turning using inertial sensors, although further validation is required for other activities and populations.
Cortical auditory distance representation based on direct-to-reverberant energy ratio
Authors: Kopco Norbert , Doreswamy Keerthi Kumar , Huang Samantha , Rossi Stephanie , Ahveninen Jyrki
Published: September 2019

Auditory distance perception and its neuronal mechanisms are poorly understood, mainly because 1) it is difficult to separate distance processing from intensity processing, 2) multiple intensity-independent distance cues are often available, and 3) the cues are combined in a context-dependent way. A recent fMRI study identified human auditory cortical area representing intensity-independent distance for sources presented along the interaural axis (Kopco et al., PNAS, 109, 11019-11024). For these sources, two intensity-independent cues are available, interaural level difference (ILD) and direct-to-reverberant energy ratio (DRR). Thus, the observed activations may have been contributed by not only distance-related, but also direction-encoding neuron populations sensitive to ILD. Here, the paradigm from the previous study was used to examine DRR-based distance representation for sounds originating in front of the listener, where ILD is not available. In a virtual environment, we performed behavioral and fMRI experiments, combined with computational analyses to identify the neural representation of distance based on DRR. The stimuli varied in distance (15-100 cm) while their received intensity was varied randomly and independently of distance. Behavioral performance showed that intensity-independent distance discrimination is accurate for frontal stimuli, even though it is worse than for lateral stimuli. fMRI activations for sounds varying in frontal distance, as compared to varying only in intensity, increased bilaterally in the posterior banks of Heschl's gyri, the planum temporale, and posterior superior temporal gyrus regions. Taken together, these results suggest that posterior human auditory cortex areas contain neuron populations that are sensitive to distance independent of intensity and of binaural cues relevant for directional hearing.

Highlights

Posterior auditory cortices (AC) are sensitive to frontally presented distance cues

These effects are independent of intensity- and direction-related binaural cues

fMRI activations to frontal distance cues are found in the right and left AC

The frontal reverberation-related auditory distance cues are behaviorally relevant
An assessment of adult mosquito collection techniques for studying species abundance and diversity in Maferinyah, Guinea
Authors: Cansado-Utrilla Cintia , Jeffries Claire L. , Kristan Mojca , Brugman Victor A. , Heard Patrick , Camara Gnepou , Sylla Moussa , Beavogui Abdoul H. , Messenger Louisa A. , Walker Thomas
Published: September 2019

Background

Guinea is a West African country with a high prevalence of vector-borne diseases where few entomological studies have been undertaken. Although several mosquito collection methods are routinely used for surveillance in vector control programmes, they target different behaviours causing bias in species diversity and abundance. Given the paucity of mosquito trap data in West Africa, we compared the performance of five trap-lure combinations and Human Landing Catches (HLCs) in Guinea.

Methods

Five mosquito traps were compared in a 5×5 Latin Square design for 15 days in three villages in Guinea between June and July 2018. CDC light traps, BG sentinel 2 traps (with BG and MB5 lures), gravid traps and Stealth traps were deployed for 24-hour intervals with mosquitoes collected every 12 hours (day and night collections). HLCs were also performed for 15 nights. A Generalised Linear Mixed Model was applied to compare the effect of the traps, sites and collection times on the mosquito abundance. Species identification was confirmed using PCR-based analysis and Sanger sequencing.

Results

In total, 10,610 mosquitoes were captured across all five traps. Significantly more mosquitoes (P<0.005) were collected by Stealth traps (7,096) compared to the rest of the traps. Stealth traps and BG sentinel 2 traps were the best at capturingAn. gambiaeandAe. aegyptimosquitoes respectively. HLCs captured predominantlyAn. coluzzii(41%) and hybrids ofAn. gambiae s.s. /An. coluzzii(36%) in contrast to the five adult traps, which captured predominantlyAn. melas(83%). Senguelen (rural) presented the highest abundance of mosquitoes and overall diversity in comparison with Fandie (semi-rural) and Maferinyah Centre One (semi-urban). To our knowledge, four species are reported for the first time in Guinea.

Conclusions

Stealth traps presented the best performance overall, suggesting that this trap may play an important role for mosquito surveillance in Guinea and similar sites in West Africa. We recommend the incorporation of molecular tools in entomological studies since it has helped to reveal, together with morphological identification, the presence of 25 mosquito species in this area.
Soil prokaryotes associated with decreasing pathogen density during anaerobic soil disinfestation
Authors: Lee Chol Gyu , Kunitomo Eriko , Iida Toshiya , Nakaho Kazuhiro , Ohkuma Moriya
Published: September 2019

Anaerobic soil disinfestation (ASD) is a chemical-independent method that can reduce pathogens. Although soil microbes play essential roles in ASD, the relationship between the microbial community structure and disinfestation efficiency remains unclear. To this end, we investigated changes in the microbial community and pathogen density during a period of ASD under field conditions for 14 days in a greenhouse using three different substrates. Soil samples were collected at 0, 3, 7, and 14 days after ASD treatment. The pathogen densities were analyzed by real-time polymerase chain reactions, prokaryotic community analysis was conducted using unidirectional pyrosequencing, and the factors related to pathogen density were statistically analyzed. The pathogen density rapidly decreased by >90% at 3 days after treatment and then slowly decreased until day 14, but the rate of decrease differed among the substrates. The microbial communities became altered after 3 days and recovered to their original state on day 14. The dipyridyl reaction, microbial diversity, richness, and community structure were not correlated with pathogen density. The most negatively correlated operational taxonomic units with pathogen density were Clostridia and Bacilli, both belonging to Firmicutes. These results suggested that the growth of specific microbes, but not the changes in microbial community structure, might be important for ASD disinfestation efficiency.
Gene Knock Up via 3’UTR editing to study gene functionin vivo
Authors: Mätlik Kärt , Olfat Soophie , Garton Daniel R. , Montaño-Rodriguez Ana , Turconi Giorgio , Porokuokka L. Lauriina , Panhelainen Anne , Schweizer Nadine , Kopra Jaakko , Cowlishaw Mark C. , Piepponen T. Petteri , Zhang Fu-Ping , Sipilä Petra , Jakobsson Johan , Andressoo Jaan-Olle
Published: September 2019

Currently available genetic tools do not allow researchers to upregulate (‘Knock Up’) the levels of a given protein while retaining its cell-type-specific regulation. As a result, we have limited ability to develop overexpression-related disease models, to study the contribution of single genes in diseases caused by copy number variations and to identify disease pathways for drug targets. Here we develop two approaches for endogenous gene upregulation:conditionalKnockUp (cKU) utilizing the Cre/lox system, and CRISPR-Cas9 mediated geneKnockUp (KU) in wild-type mouse embryos and human cells. Using glial cell line derived neurotrophic factor (GDNF) as a proof of concept, we show that both approaches resulted in upregulation of endogenous GDNF levels without disturbingGdnf’s expression pattern. Furthermore, CNS-specific GDNF cKU resulted in dopaminergic abnormalities and schizophrenia-like phenotypes. Our results suggest that gene Knock Up can reveal unknown gene functions and provide novel entry points for studying neurological disease.
Resting-State Functional Networks of Different Topographic Representations in the Somatosensory Cortex of Macaque Monkeys and Humans
Authors: Thomas John , Sharma Dixit , Mohanta Sounak , Jain Neeraj
Published: September 2019

Information processing in the brain is mediated through a complex functional network architecture whose comprising nodes integrate and segregate themselves on different timescales. To gain an understanding of the network function it is imperative to identify and understand the network structure with respect to the underlying anatomical connectivity and the topographic organization. Here we show that the previously described resting-state network for the somatosensory area 3b comprises of distinct networks that are characteristic for different topographic representations. Seed-based resting-state functional connectivity analysis in macaque monkeys and humans using BOLD-fMRI signals from the face, the hand and rest of the medial somatosensory representations of area 3b revealed different correlation patterns. Both monkeys and humans have many similarities in the connectivity networks, although the networks are more complex in humans with many more nodes. In both the species face area network has the highest ipsilateral and contralateral connectivity, which included areas 3b and 4, and ventral premotor area. The area 3b hand network included ipsilateral hand representation in area 4.

The emergent functional network structures largely reflect the known anatomical connectivity. Our results show that different body part representations in area 3b have independent functional networks perhaps reflecting differences in the behavioral use of different body parts. The results also show that large cortical areas if considered together, do not give a complete and accurate picture of the network architecture.

Highlights

Somatosensory resting-state functional network is not uniform across the entire area 3b. Different body part representations have different connectivity networks.

These functional connectivity networks have many similarities in the two primate species, i.e. macaque monkeys and humans, although the human network is more complex.

In both the species network of the face representation is most extensive, which includes ipsilateral face motor cortex and PMv in both hemispheres.

The hand representation in area 3b has connectivity with ipsilateral hand motor cortex.

Bilateral connectivity with homologous and nonhomologous area 3b representations was observed only in humans.

The functional connectivity networks largely reflect the underlying anatomical connectivity.