bluuebunny/crossref_metadata_2025 huggingface dataset:
Meroplankton Diversity, Seasonality and Life-History Traits Across the Barents Sea Polar Front Revealed by High-Throughput DNA Barcoding
Authors: Descôteaux Raphaëlle , Ershova Elizaveta , Wangensteen Owen S. , Præbel Kim , Renaud Paul E. , Cottier Finlo , Bluhm Bodil A.
Published: May 2021

In many species of marine benthic invertebrates, a planktonic larval phase plays a critical role in dispersal. Very little is known about the larval biology of most species, however, in part because species identification has historically been hindered by the microscopic size and morphological similarity among related taxa. This study aimed to determine the taxonomic composition and seasonal distribution of meroplankton in the Barents Sea, across the Polar Front. We collected meroplankton during five time points seasonally and used high-throughput DNA barcoding of individual larvae to obtain species-level information on larval seasonality. We found that meroplankton was highly diverse (72 taxa from eight phyla) and present in the Barents Sea year-round with a peak in abundance in August and November, defying the conventional wisdom that peak abundance would coincide with the spring phytoplankton bloom. Ophiuroids, bivalves, and polychaetes dominated larval abundance while gastropods and polychaetes accounted for the bulk of the taxon diversity. Community structure varied seasonally and total abundance was generally higher south of the Polar Front while taxon richness was overall greater to the north. Of the species identified, most were known inhabitants of the Barents Sea. However, the nemertean Cephalothrix iwatai and the brittle star Ophiocten gracilis were abundant in the meroplankton despite never having been previously recorded in the northern Barents Sea. The new knowledge on seasonal patterns of individual meroplanktonic species has implications for understanding environment-biotic interactions in a changing Arctic and provides a framework for early detection of potential newcomers to the system.
Sex-Based Differences in pH Parameters and Esophageal Impedance of Patients With Gastroesophageal Reflux Disease
Authors: Ye Bixing , Wang Yanjuan , Lin Lin , Jiang Liuqin , Wang Meifeng
Published: May 2021

Background/Aims: The incidence of reflux esophagitis (RE) has a striking predominance in males. Conversely, non-erosive reflux disease (NERD) is more common in females. This imbalance of gastroesophageal reflux disease (GERD) implies sex-related differences in its pathogenesis. However, limited studies have analyzed the sex-based differences in pH parameters and esophageal impedance of GERD patients.

Methods: This study evaluated sex-based pathogenesis differences by comparing reflux episodes, mean nocturnal baseline impedance (MNBI) values, and post-reflux swallow-induced peristaltic wave (PSPW) index values of males with GERD and females with GERD using 24-h multichannel intraluminal impedance and pH monitoring.

Results: We analyzed 181 patients (102 males and 79 females) with GERD. Reflux symptom index (RSI) scores were higher in females than that in males (P < 0.05). Males had significantly longer acid exposure times, higher DeMeester scores, and more acid reflux episodes than females (P < 0.05). Females had more instances of weakly acidic reflux than males (P < 0.01). The PSPW index values of males and females were similar (P > 0.05). Compared with females, males had lower MNBI values for the mid and distal esophagus (P < 0.05). However, with increasing age, the MNBI values of females decreased more rapidly than those of males. MNBI values of elderly patients of both sexes older than 60 years were similar.

Conclusions: Acid reflux is more likely to occur in males; however, females tend to have more instances of weakly acid reflux. The integrity of the esophageal mucosa is more fragile in males than in females; however, the esophageal mucosal barrier attenuates more rapidly with increasing age in females than in males.
ECMO Rescues Patients With Acute Respiratory Failure Related to GPA
Authors: Wan Rongjun , Yang Wenzhe , Ma Xinhua , Yang Wei , Pan Pinhua , Hu Chengping , Chen Qiong , Zhou Yaou , Lu Rongli , Fang Yimin , Li Yuanyuan
Published: May 2021

Granulomatosis with polyangiitis (GPA) is a subtype of anti-neutrophil cytoplasmic antibody-associated vasculitis with a wide range of clinical symptoms related to the systemic involvement of small blood vessels. The respiratory system is one of the most frequently involved, and life-threatening acute respiratory failure could occur due to diffusive alveolar hemorrhage and tracheal stenosis. When maximum mechanical ventilation is unable to maintain oxygenation, extracorporeal membrane oxygenation (ECMO) should be considered as the final respiratory supportive method, if available. Here we present a 32-year-old male patient with acute respiratory failure (ARF) related to GPA, who was rescued by winning time for accurate diagnosis and appropriate treatment. Additionally, we reviewed more than 60 GPA-related ARF cases on multiple online databases, summarized the clinical manifestations of these patients, and concluded that ECMO plays an important role in further respiratory support for ARF patients with GPA and assists in accurate and timely diagnosis and appropriate treatment, thus helping them recuperate.
Useful Ultrasonographic Parameters to Predict Difficult Laryngoscopy and Difficult Tracheal Intubation—A Systematic Review and Meta-Analysis
Authors: Gomes Sara H. , Simões Ana M. , Nunes Andreia M. , Pereira Marta V. , Teoh Wendy H. , Costa Patrício S. , Kristensen Michael S. , Teixeira Pedro M. , Pêgo José Miguel
Published: May 2021

Unexpected difficult airway management can cause significant morbidity and mortality in patients admitted for elective procedures. Ultrasonography is a promising tool for perioperative airway assessment, nevertheless it is still unclear which sonographic parameters are useful predictors of difficult laryngoscopy and tracheal intubation. To determine the ultrasonographic predictors of a difficult airway that could be applied for routine practice, a systematic review and meta-analysis was conducted. Literature search was performed on PubMED, Web of Science and Embase using the selected keywords. Human primary studies, published in English with the use of ultrasonography to prediction of difficult laryngoscopy or tracheal intubation were included. A total of 19 articles (4,570 patients) were analyzed for the systematic review and 12 articles (1,141 patients) for the meta-analysis. Standardized mean differences between easy and difficult laryngoscopy groups were calculated and the parameter effect size quantified. A PRISMA methodology was used and the critical appraisal tool from Joanna Briggs Institute was applied. Twenty-six sonographic parameters were studied. The overall effect of the distance from skin to hyoid bone (p = 0.02); skin to epiglottis (p = 0.02); skin to the anterior commissure of vocal cords (p = 0.02), pre-epiglottis space to distance between epiglottis and midpoint between vocal cords (p = 0.01), hyomental distance in neutral (p < 0.0001), and extended (p = 0.0002) positions and ratio of hyomental distance in neutral to extended (p = 0.001) was significant. This study shows that hyomental distance in the neutral position is the most reliable parameter for pre-operative airway ultrasound assessment. The main limitations of the study are the small sample size, heterogeneity of studies, and absence of a standardized ultrasonographic evaluation method [Registered at International prospective register of systematic reviews (PROSPERO): number 167931].
Emerging Radionuclides in a Regulatory Framework for Medicinal Products – How Do They Fit?
Authors: Decristoforo Clemens , Neels Oliver , Patt Marianne
Published: May 2021

Recent years have seen the establishment of several radionuclides as medicinal products in particular in the setting of theranostics and PET. [177Lu]Lutetium Chloride or [64Cu]Copper Chloride have received marketing authorization as radionuclide precursor, [68Ga]Gallium Chloride has received regulatory approval in the form of different 68Ge/68Ga generators. This is a formal requirement by the EU directive 2001/83, even though for some of these radionuclide precursors no licensed kit is available that can be combined to obtain a final radiopharmaceuticals, as it is the case for Technetium-99m. In view of several highly promising, especially metallic radionuclides for theranostic applications in a wider sense, the strict regulatory environment poses the risk of slowing down development, in particular for radionuclide producers that want to provide innovative radionuclides for clinical research purposes, which is the basis for their further establishment. In this paper we address the regulatory framework for novel radionuclides within the EU, the current challenges in particular related to clinical translation and potential options to support translational development within Europe and worldwide.
Respiratory Co-Infections: Modulators of SARS-CoV-2 Patients’ Clinical Sub-Phenotype
Authors: Mehta Priyanka , Sahni Shweta , Siddiqui Samreen , Mishra Neha , Sharma Pooja , Sharma Sachin , Tyagi Akansha , Chattopadhyay Partha , Vivekanand A , Devi Priti , Khan Azka , Waghdhare Swati , Budhiraja Sandeep , Uppili Bharathram , Maurya Ranjeet , Nangia Vivek , Shamim Uzma , Hazarika Pranjal P. , Wadhwa Saruchi , Tyagi Nishu , Dewan Arun , Tarai Bansidhar , Das Poonam , Faruq Mohammed , Agrawal Anurag , Jha Sujeet , Pandey Rajesh
Published: May 2021

Co-infection with ancillary pathogens is a significant modulator of morbidity and mortality in infectious diseases. There have been limited reports of co-infections accompanying SARS-CoV-2 infections, albeit lacking India specific study. The present study has made an effort toward elucidating the prevalence, diversity and characterization of co-infecting respiratory pathogens in the nasopharyngeal tract of SARS-CoV-2 positive patients. Two complementary metagenomics based sequencing approaches, Respiratory Virus Oligo Panel (RVOP) and Holo-seq, were utilized for unbiased detection of co-infecting viruses and bacteria. The limited SARS-CoV-2 clade diversity along with differential clinical phenotype seems to be partially explained by the observed spectrum of co-infections. We found a total of 43 bacteria and 29 viruses amongst the patients, with 18 viruses commonly captured by both the approaches. In addition to SARS-CoV-2, Human Mastadenovirus, known to cause respiratory distress, was present in a majority of the samples. We also found significant differences of bacterial reads based on clinical phenotype. Of all the bacterial species identified, ∼60% have been known to be involved in respiratory distress. Among the co-pathogens present in our sample cohort, anaerobic bacteria accounted for a preponderance of bacterial diversity with possible role in respiratory distress. Clostridium botulinum, Bacillus cereus and Halomonas sp. are anaerobes found abundantly across the samples. Our findings highlight the significance of metagenomics based diagnosis and detection of SARS-CoV-2 and other respiratory co-infections in the current pandemic to enable efficient treatment administration and better clinical management. To our knowledge this is the first study from India with a focus on the role of co-infections in SARS-CoV-2 clinical sub-phenotype.
Interactions Between Tsetse Endosymbionts and Glossina pallidipes Salivary Gland Hypertrophy Virus in Glossina Hosts
Authors: Demirbas-Uzel Güler , Augustinos Antonios A. , Doudoumis Vangelis , Parker Andrew G. , Tsiamis George , Bourtzis Kostas , Abd-Alla Adly M. M.
Published: May 2021

Tsetse flies are the sole cyclic vector for trypanosomosis, the causative agent for human African trypanosomosis or sleeping sickness and African animal trypanosomosis or nagana. Tsetse population control is the most efficient strategy for animal trypanosomosis control. Among all tsetse control methods, the Sterile Insect Technique (SIT) is one of the most powerful control tactics to suppress or eradicate tsetse flies. However, one of the challenges for the implementation of SIT is the mass production of target species. Tsetse flies have a highly regulated and defined microbial fauna composed of three bacterial symbionts (Wigglesworthia, SodalisandWolbachia) and a pathogenicGlossina pallidipesSalivary Gland Hypertrophy Virus (GpSGHV) which causes reproduction alterations such as testicular degeneration and ovarian abnormalities with reduced fertility and fecundity. Interactions between symbionts and GpSGHV might affect the performance of the insect host. In the present study, we assessed the possible impact of GpSGHV on the prevalence of tsetse endosymbionts under laboratory conditions to decipher the bidirectional interactions on sixGlossinalaboratory species. The results indicate that tsetse symbiont densities increased over time in tsetse colonies with no clear impact of the GpSGHV infection on symbionts density. However, a positive correlation between the GpSGHV andSodalisdensity was observed inGlossina fuscipesspecies. In contrast, a negative correlation between the GpSGHV density and symbionts density was observed in the other taxa. It is worth noting that the lowestWigglesworthiadensity was observed inG. pallidipes, the species which suffers most from GpSGHV infection. In conclusion, the interactions between GpSGHV infection and tsetse symbiont infections seems complicated and affected by the host and the infection density of the GpSGHV and tsetse symbionts.
Transcriptome Analysis Reveals Cr(VI) Adaptation Mechanisms in Klebsiella sp. Strain AqSCr
Authors: Lara Paloma , Vega-Alvarado Leticia , Sahonero-Canavesi Diana X. , Koenen Michel , Villanueva Laura , Riveros-Mckay Fernando , Morett Enrique , Juárez Katy
Published: May 2021

Klebsiella sp. strain AqSCr, isolated from Cr(VI)-polluted groundwater, reduces Cr(VI) both aerobically and anaerobically and resists up 34 mM Cr(VI); this resistance is independent of the ChrA efflux transporter. In this study, we report the whole genome sequence and the transcriptional profile by RNA-Seq of strain AqSCr under Cr(VI)-adapted conditions and found 255 upregulated and 240 downregulated genes compared to controls without Cr(VI) supplementation. Genes differentially transcribed were mostly associated with oxidative stress response, DNA repair and replication, sulfur starvation response, envelope-osmotic stress response, fatty acid (FA) metabolism, ribosomal subunits, and energy metabolism. Among them, genes not previously associated with chromium resistance, for example, cybB, encoding a putative superoxide oxidase (SOO), gltA2, encoding an alternative citrate synthase, and des, encoding a FA desaturase, were upregulated. The sodA gene encoding a manganese superoxide dismutase was upregulated in the presence of Cr(VI), whereas sodB encoding an iron superoxide dismutase was downregulated. Cr(VI) resistance mechanisms in strain AqSCr seem to be orchestrated by the alternative sigma factors fecl, rpoE, and rpoS (all of them upregulated). Membrane lipid analysis of the Cr(IV)-adapted strain showed a lower proportion of unsaturated lipids with respect to the control, which we hypothesized could result from unsaturated lipid peroxidation followed by degradation, together with de novo synthesis mediated by the upregulated FA desaturase-encoding gene, des. This report helps to elucidate both Cr(VI) toxicity targets and global bacterial response to Cr(VI).
Research Progress on Phytopathogenic Fungi and Their Role as Biocontrol Agents
Authors: Peng Yan , Li Shi J. , Yan Jun , Tang Yong , Cheng Jian P. , Gao An J. , Yao Xin , Ruan Jing J. , Xu Bing L.
Published: May 2021

Phytopathogenic fungi decrease crop yield and quality and cause huge losses in agricultural production. To prevent the occurrence of crop diseases and insect pests, farmers have to use many synthetic chemical pesticides. The extensive use of these pesticides has resulted in a series of environmental and ecological problems, such as the increase in resistant weed populations, soil compaction, and water pollution, which seriously affect the sustainable development of agriculture. This review discusses the main advances in research on plant-pathogenic fungi in terms of their pathogenic factors such as cell wall-degrading enzymes, toxins, growth regulators, effector proteins, and fungal viruses, as well as their application as biocontrol agents for plant pests, diseases, and weeds. Finally, further studies on plant-pathogenic fungal resources with better biocontrol effects can help find new beneficial microbial resources that can control diseases.
Zoantharian Endosymbiont Community Dynamics During a Stress Event
Authors: Fujiwara Yu , Kawamura Iori , Reimer James Davis , Parkinson John Everett
Published: May 2021

Coral reefs are complex ecosystems composed of many interacting species. One ecologically important group consists of zoantharians, which are closely related to reef-building corals. Like corals, zoantharians form mutualistic symbioses with dinoflagellate micro-algae (family Symbiodiniaceae), but their associations remain underexplored. To examine the degree to which zoantharians exhibit altered symbiont dynamics under changing environmental conditions, we reciprocally transplanted colonies of Zoanthus sansibaricus between intertidal (2 m) and subtidal (26 m) depths within a reef in Okinawa, Japan. At this location, Z. sansibaricus can associate with three Symbiodiniaceae species from two genera distributed along a light and depth gradient. We developed species-specific molecular assays and sampled colonies pre‐ and post-transplantation to analyze symbiont community diversity. Despite large environmental differences across depths, we detected few symbiont compositional changes resulting from transplantation stress. Colonies sourced from the intertidal zone associated with mixtures of a “shallow” Symbiodinium sp. and a “shallow” Cladocopium sp. independent of whether they were transplanted to shallow or deep waters. Colonies sourced from the subtidal zone were dominated by a “deep” Cladocopium sp. regardless of transplant depth. Subtidal colonies brought to shallow depths did not transition to the presumably high-light adapted shallow symbionts present in the new environment, but rather bleached and died. These patterns mirror observations of highly stable coral-algal associations subjected to depth transplantation. Our results indicate that Zoanthus-Symbiodiniaceae symbioses remain stable despite stress, suggesting these important reef community members have relatively low capacity to shuffle to more stress-tolerant micro-algae in response to ongoing climate change.
Metabolome and Microbiota Analysis Reveals the Conducive Effect of Pediococcus acidilactici BCC-1 and Xylan Oligosaccharides on Broiler Chickens
Authors: Wu Yuqin , Lei Zhao , Wang Youli , Yin Dafei , Aggrey Samuel E. , Guo Yuming , Yuan Jianmin
Published: May 2021

Xylan oligosaccharides (XOS) can promote proliferation of Pediococcus acidilactic BCC-1, which benefits gut health and growth performance of broilers. The study aimed to investigate the effect of Pediococcus acidilactic BCC-1 (referred to BBC) and XOS on the gut metabolome and microbiota of broilers. The feed conversion ratio of BBC group, XOS group and combined XOS and BBC groups was lower than the control group (P < 0.05). Combined XOS and BBC supplementation (MIX group) elevated butyrate content of the cecum (P < 0.05) and improved ileum morphology by enhancing the ratio of the villus to crypt depth (P < 0.05). The 16S rDNA results indicated that both XOS and BBC induced high abundance of butyric acid bacteria. XOS treatment elevated Clostridium XIVa and the BBC group enriched Anaerotruncus and Faecalibacterium. In contrast, MIX group induced higher relative abundance of Clostridiaceae XIVa, Clostridiaceae XIVb and Lachnospiraceae. Besides, MIX group showed lower abundance of pathogenic bacteria such as Campylobacter. Metabolome analysis showed that all the 3 treatment groups (XOS, BBC and MIX) showed lower concentrations of sorbitol and both XOS and BBC group had higher concentrations of pyridoxine levels than CT group. Besides, XOS and BBC groups enhanced the content of hydroxyphenyl derivatives 4-hydroxyphenylpyruvate 1 and 3-(3-hydroxyphenyl) propionic acid, respectively (P < 0.05). Notably, MIX group enhanced both 4-hydroxyphenylpyruvate 1 and 3-(3-hydroxyphenyl) propionic acid (P < 0.05). Thus, XOS and BBC may have a synergistic role to improve the performance of broilers by modulating gut microbiota and metabolome.
Conserved RNA Binding Activity of Phosphatidyl Inositol 5-Phosphate 4-Kinase (PIP4K2A)
Authors: Behari Jatin , Borkar Pranita , Vindu Arya , Dandewad Vishal , Upadrasta Sindhuri , Shanmugam Dhanasekaran , Seshadri Vasudevan
Published: May 2021

Plasmodium falciparum is a causative agent for malaria and has a complex life cycle in human and mosquito hosts. During its life cycle, the malarial parasite Plasmodium goes through different asexual and sexual stages, in humans and mosquitoes. Expression of stage-specific proteins is important for successful completion of its life cycle and requires tight gene regulation. In the case of Plasmodium, due to relative paucity of the transcription factors, it is postulated that posttranscriptional regulation plays an important role in stage-specific gene expression. Translation repression of specific set of mRNA has been reported in gametocyte stages of the parasite. A conserved element present in the 3′UTR of some of these transcripts was identified. Phosphatidylinositol 5-phosphate 4-kinase (PIP4K2A) was identified as the protein that associates with these RNA. We now show that the RNA binding activity of PIP4K2A is independent of its kinase activity. We also observe that PIP4K2A is imported into the parasite from the host on Plasmodium berghei and Toxoplasma gondii. The RNA binding activity of PIP4K2A seems to be conserved across species from Drosophila and C. elegans to humans, suggesting that the RNA binding activity of PIP4K may be important, and there may be host transcripts that may be regulated by PIP4K2A. These results identify a novel RNA binding role for PIP4K2A that may not only play a role in Plasmodium propagation but may also function in regulating gene expression in multicellular organisms.
Longitudinal Profiles of Dietary and Microbial Metabolites in Formula- and Breastfed Infants
Authors: Sillner Nina , Walker Alesia , Lucio Marianna , Maier Tanja V. , Bazanella Monika , Rychlik Michael , Haller Dirk , Schmitt-Kopplin Philippe
Published: May 2021

The early-life metabolome of the intestinal tract is dynamically influenced by colonization of gut microbiota which in turn is affected by nutrition, i.e. breast milk or formula. A detailed examination of fecal metabolites was performed to investigate the effect of probiotics in formula compared to control formula and breast milk within the first months of life in healthy neonates. A broad metabolomics approach was conceptualized to describe fecal polar and semi-polar metabolites affected by feeding type within the first year of life. Fecal metabolomes were clearly distinct between formula- and breastfed infants, mainly originating from diet and microbial metabolism. Unsaturated fatty acids and human milk oligosaccharides were increased in breastfed, whereas Maillard products were found in feces of formula-fed children. Altered microbial metabolism was represented by bile acids and aromatic amino acid metabolites. Elevated levels of sulfated bile acids were detected in stool samples of breastfed infants, whereas secondary bile acids were increased in formula-fed infants. Microbial co-metabolism was supported by significant correlation between chenodeoxycholic or lithocholic acid and members of Clostridia. Fecal metabolites showed strong inter- and intra-individual behavior with features uniquely present in certain infants and at specific time points. Nevertheless, metabolite profiles converged at the end of the first year, coinciding with solid food introduction.
Posttranslational Modifications of the Mineralocorticoid Receptor and Cardiovascular Aging
Authors: Gadasheva Yekatarina , Nolze Alexander , Grossmann Claudia
Published: May 2021

During aging, the cardiovascular system is especially prone to a decline in function and to life-expectancy limiting diseases. Cardiovascular aging is associated with increased arterial stiffness and vasoconstriction as well as left ventricular hypertrophy and reduced diastolic function. Pathological changes include endothelial dysfunction, atherosclerosis, fibrosis, hypertrophy, inflammation, and changes in micromilieu with increased production of reactive oxygen and nitrogen species. The renin-angiotensin-aldosterone-system is an important mediator of electrolyte and blood pressure homeostasis and a key contributor to pathological remodeling processes of the cardiovascular system. Its effects are partially conveyed by the mineralocorticoid receptor (MR), a ligand-dependent transcription factor, whose activity increases during aging and cardiovascular diseases without correlating changes of its ligand aldosterone. There is growing evidence that the MR can be enzymatically and non-enzymatically modified and that these modifications contribute to ligand-independent modulation of MR activity. Modifications reported so far include phosphorylation, acetylation, ubiquitination, sumoylation and changes induced by nitrosative and oxidative stress. This review focuses on the different posttranslational modifications of the MR, their impact on MR function and degradation and the possible implications for cardiovascular aging and diseases.
Role of Fibrinolytic Enzymes in Anti-Thrombosis Therapy
Authors: Altaf Farwa , Wu Shourong , Kasim Vivi
Published: May 2021

Thrombosis, a major cause of deaths in this modern era responsible for 31% of all global deaths reported by WHO in 2017, is due to the aggregation of fibrin in blood vessels which leads to myocardial infarction or other cardiovascular diseases (CVDs). Classical agents such as anti-platelet, anti-coagulant drugs or other enzymes used for thrombosis treatment at present could leads to unwanted side effects including bleeding complication, hemorrhage and allergy. Furthermore, their high cost is a burden for patients, especially for those from low and middle-income countries. Hence, there is an urgent need to develop novel and low-cost drugs for thrombosis treatment. Fibrinolytic enzymes, including plasmin like proteins such as proteases, nattokinase, and lumbrokinase, as well as plasminogen activators such as urokinase plasminogen activator, and tissue-type plasminogen activator, could eliminate thrombi with high efficacy rate and do not have significant drawbacks by directly degrading the fibrin. Furthermore, they could be produced with high-yield and in a cost-effective manner from microorganisms as well as other sources. Hence, they have been considered as potential compounds for thrombosis therapy. Herein, we will discuss about natural mechanism of fibrinolysis and thrombus formation, the production of fibrinolytic enzymes from different sources and their application as drugs for thrombosis therapy.
Lack of Spinal Neuropeptide Y Is Involved in Mechanical Itch in Aged Mice
Authors: Cui Huan , Su Wenliang , Cao Yan , Ma Lulu , Xu Guangyan , Mou Wanying , Zhang Hanlin , Yu Jiawen , Ma Chao , Zhang Xiuhua , Huang Yuguang
Published: May 2021

Neuropeptide Y (NPY) signaling plays an essential role in gating the pruritic afferent information in the spinal cord. Recent studies revealed that the aging process down-regulated the expression of NPY in the central nervous system. We propose that the lack of spinal NPY may be involved in certain types of pruritus in the elderly population. This study was designed to investigate the role of NPY in aging-induced itch using the senile mouse model. The expression of NPY in the spinal dorsal horn was compared between young (2 months old) and aged (24 months old) mice. Western blotting and immunohistochemistry showed that the expression of NPY was significantly reduced in the spinal dorsal horn in aged mice. In addition, a neuronal maker of apoptosis, TUNEL, was detected in the NPY positive neurons only in the aged spinal cord. Behavioral assay indicated that light mechanical stimulus evoked significantly more scratching in the aged than in the young mice, whereas chemical-evoked itch and pain-related behaviors were not altered. Intrathecal injection of either NPY or LP-NPY, a NPY receptor 1 (NPY1R) agonist, significantly alleviated the mechanically evoked itch in aged mice without altering the responses to chemical pruritogens. Our study suggested that downregulation of spinal NPY in the aged mice might play a role in the higher incidence of the mechanically evoked itch than that in the young mice. Therapies targeting the NPY system might serve as a potential strategy for alleviating the pruritic symptoms among the elderly population.
The Role of Microglia in Perioperative Neuroinflammation and Neurocognitive Disorders
Authors: Saxena Sarah , Kruys Veronique , Vamecq Joseph , Maze Mervyn
Published: May 2021

The aseptic trauma of peripheral surgery activates a systemic inflammatory response that results in neuro-inflammation; the microglia, the resident immunocompetent cells in the brain, are a key element of the neuroinflammatory response. In most settings microglia perform a surveillance role in the brain detecting and responding to “invaders” to maintain homeostasis. However, microglia have also been implicated in producing harm possibly by changing its phenotype from its beneficial, anti-inflammatory state (termed M2) into an injurious pro-inflammatory state (termed M1); it is likely that there are intermediates states between these polar phenotypes and some consider that a gradient exists with a number of intermediates, rather than a strict dichotomy between M1 and M2. In the pro-inflammatory phenotypes, microglia can disrupt synaptic plasticity such as long- term potentiation that can result in disorders of learning and memory of the type observed in Peri-operative Neurocognitive Disorders. Therefore, investigators have sought strategies to prevent microglia from provoking this adverse event in the perioperative period. In preclinical studies microglia can be depleted by removing trophic factors required for its maintenance; subsequent repopulation with a more beneficial microglial phenotype may result in memory enhancement, improved sensory motor function, as well as suppression of neuroinflammatory and oxidative stress pathways. Another approach consists of preventing microglial activation using the non-specific P38 MAP kinase blockers such as minocycline. Perhaps a more physiologic approach is the use of inhibitors of potassium (K+) channels that are required to convert the microglia into an active state. In this context the specific K+ channels that are implicated are termed Kv1.3 and KCa3.1 and high selective inhibitors for each have been developed. Data are accumulating demonstrating the utility of these K+ channel blockers in preventing Perioperative Neurocognitive Disorders.
The Iterative Learning Gain That Optimizes Real-Time Torque Tracking for Ankle Exoskeletons in Human Walking Under Gait Variations
Authors: Zhang Juanjuan , Collins Steven H.
Published: May 2021

Lower-limb exoskeletons often use torque control to manipulate energy flow and ensure human safety. The accuracy of the applied torque greatly affects how well the motion is assisted and therefore improving it is always of interest. Feed-forward iterative learning, which is similar to predictive stride-wise integral control, has proven an effective compensation to feedback control for torque tracking in exoskeletons with complicated dynamics during human walking. Although the intention of iterative learning was initially to benefit average tracking performance over multiple strides, we found that, after proper gain tuning, it can also help improve real-time torque tracking. We used theoretical analysis to predict an optimal iterative-learning gain as the inverse of the passive actuator stiffness. Walking experiments resulted in an optimum gain equal to 0.99 ± 0.38 times the predicted value, confirming our hypothesis. The results of this study provide guidance for the design of torque controllers in robotic legged locomotion systems and will help improve the performance of robots that assist gait.
A Clinical Decision-Making Framework for the Use of Video Gaming as a Therapeutic Modality
Authors: Espy Debbie , Reinthal Ann , Dal Bello-Haas Vanina
Published: May 2021

Virtual reality and video gaming offer modulation of more exercise and motor learning parameters simultaneously than other modalities; however, there is a demonstrated need for resources to facilitate their effective use clinically. This article presents a conceptual framework to guide clinical-decision making for the selection, adaptation, modulation, and progression of virtual reality or gaming when used as a therapeutic exercise modality, and two cases as exemplars. This framework was developed by adapting the steps of theory derivation, whereby concepts and parent theories are brought together to describe a new structure or phenomenon of interest. Specifically, motor learning theory, integrated motor control theory, Gentile's Taxonomy of Tasks, and therapeutic exercise principles were integrated to develop this framework. It incorporates person (body segment), environmental, and task demands; each demand is comprised of realm, category, choice, and continuum parameters as motor training considerations and alternatives for decision-making. This framework: (1) provides structure to guide clinical decisions for effective and safe use of virtual reality or gaming to meet therapeutic goals and requirements, (2) is a concise and organized method to identify, document, and track the therapeutic components of protocols and client progression over time; (3) can facilitate documentation for reimbursement and communication among clinicians; and, (4) structures student learning, and (5) informs research questions and methods.
Scalable Bio Marker Combinations for Early Stroke Diagnosis: A Systematic Review
Authors: Baez Saiyet de la C. , García del Barco Diana , Hardy-Sosa Anette , Guillen Nieto Gerardo , Bringas-Vega Maria Luisa , Llibre-Guerra Jorge J. , Valdes-Sosa Pedro
Published: May 2021

Background: Acute stroke treatment is a time-critical process in which every minute counts. Laboratory biomarkers are needed to aid clinical decisions in the diagnosis. Although imaging is critical for this process, these biomarkers may provide additional information to distinguish actual stroke from its mimics and monitor patient condition and the effect of potential neuroprotective strategies. For such biomarkers to be effectively scalable to public health in any economic setting, these must be cost-effective and non-invasive. We hypothesized that blood-based combinations (panels) of proteins might be the key to this approach and explored this possibility through a systematic review.

Methods: We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines for systematic review. Initially, the broader search for biomarkers for early stroke diagnosis yielded 704 hits, and five were added manually. We then narrowed the search to combinations (panels) of the protein markers obtained from the blood.

Results: Twelve articles dealing with blood-based panels of protein biomarkers for stroke were included in the systematic review. We observed that NR2 peptide (antibody against the NR2 fragment) and glial fibrillary acidic protein (GFAP) are brain-specific markers related to stroke. Von Willebrand factor (vWF), matrix metalloproteinase 9 (MMP-9), and S100β have been widely used as biomarkers, whereas others such as the ischemia-modified albumin (IMA) index, antithrombin III (AT-III), and fibrinogen have not been evaluated in combination. We herein propose the following new combination of biomarkers for future validation: panel 1 (NR2 + GFAP + MMP-9 + vWF + S100β), panel 2 (NR2 + GFAP + MMP-9 + vWF + IMA index), and panel 3 (NR2 + GFAP + AT-III + fibrinogen).

Conclusions: More research is needed to validate, identify, and introduce these panels of biomarkers into medical practice for stroke recurrence and diagnosis in a scalable manner. The evidence indicates that the most promising approach is to combine different blood-based proteins to provide diagnostic precision for health interventions. Through our systematic review, we suggest three novel biomarker panels based on the results in the literature and an interpretation based on stroke pathophysiology.
Case Report: Late Successful Thrombectomy for Ischemic Stroke in a 2-Year-Old Child
Authors: Nasr Nathalie , Delamarre Louis , Cheuret Emmanuel , Chausseray Gerald , Olivot Jean Marc , Acar Philippe , Bonneville Fabrice
Published: May 2021

Despite extensive evidence of benefit of thrombectomy in adult ischemic stroke due to large-vessel occlusion in the 6-h window, its role remains uncertain in very young children. We describe hereafter the case of a 2-year-old female child who had a successful thrombectomy 9 h after stroke onset. The patient presented with right hemiplegia, central facial palsy, a normal level of consciousness, and speech difficulties. The PedNIHS score was 11. CT scan without contrast injection displayed spontaneous hyperdensity of the middle cerebral artery (MCA), with only limited early signs of ischemia (ASPECTS 8). CT angiography demonstrated occlusion of the proximal MCA with good collaterals. Thrombectomy was realized. Complete recanalization (TICI 3) was obtained under general anesthesia after two passes of a stent retriever. Time from symptoms onset to full recanalization was 9 h. The acute ischemic stroke was caused by embolic thrombus from a congenital heart disease. Clinical recovery was complete. Three months after the thrombectomy, the young patient was doing well without any neurological sequelae (PedNIHSS 0; modified Rankin Scale: 0). This case report is an example of a decision-making process to perform thrombectomy in a very young child, which included cardio-embolic etiology as a parameter that potentially might have participated to the successful outcome of the therapeutic procedure.
Pulsed Infrared Stimulation of Vertical Semicircular Canals Evokes Cardiovascular Changes in the Rat
Authors: Rice Darrian , Martinelli Giorgio P. , Jiang Weitao , Holstein Gay R. , Rajguru Suhrud M.
Published: May 2021

A variety of stimuli activating vestibular end organs, including sinusoidal galvanic vestibular stimulation, whole body rotation and tilt, and head flexion have been shown to evoke significant changes in blood pressure (BP) and heart rate (HR). While a role for the vertical semicircular canals in altering autonomic activity has been hypothesized, studies to-date attribute the evoked BP and HR responses to the otolith organs. The present study determined whether unilateral activation of the posterior (PC) or anterior (AC) semicircular canal is sufficient to elicit changes in BP and/or HR. The study employed frequency-modulated pulsed infrared radiation (IR: 1,863 nm) directed via optical fibers to PC or AC of adult male Long-Evans rats. BP and HR changes were detected using a small-animal single pressure telemetry device implanted in the femoral artery. Eye movements evoked during IR of the vestibular endorgans were used to confirm the stimulation site. We found that sinusoidal IR delivered to either PC or AC elicited a rapid decrease in BP and HR followed by a stimulation frequency-matched modulation. The magnitude of the initial decrements in HR and BP did not correlate with the energy of the suprathreshold stimulus. This response pattern was consistent across multiple trials within an experimental session, replicable, and in most animals showed no evidence of habituation or an additive effect. Frequency modulated electrical current delivered to the PC and IR stimulation of the AC, caused decrements in HR and BP that resembled those evoked by IR of the PC. Frequency domain heart rate variability assessment revealed that, in most subjects, IR stimulation increased the low frequency (LF) component and decreased the high frequency (HF) component, resulting in an increase in the LF/HF ratio. This ratio estimates the relative contributions of sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activities. An injection of atropine, a muscarinic cholinergic receptor antagonist, diminished the IR evoked changes in HR, while the non-selective beta blocker propranolol eliminated changes in both HR and BP. This study provides direct evidence that activation of a single vertical semicircular canal is sufficient to activate and modulate central pathways that control HR and BP.
Investigating Nuisance Effects Induced in EEG During tACS Application
Authors: Holzmann Romain , Koppehele-Gossel Judith , Voss Ursula , Klimke Ansgar
Published: May 2021

Transcranial alternating-current stimulation (tACS) in the frequency range of 1–100 Hz has come to be used routinely in electroencephalogram (EEG) studies of brain function through entrainment of neuronal oscillations. It turned out, however, to be highly non-trivial to remove the strong stimulation signal, including its harmonic and non-harmonic distortions, as well as various induced higher-order artifacts from the EEG data recorded during the stimulation. In this paper, we discuss some of the problems encountered and present methodological approaches aimed at overcoming them. To illustrate the mechanisms of artifact induction and the proposed removal strategies, we use data obtained with the help of a schematic demonstrator setup as well as human-subject data.
Dl-3-n-Butylphthalide Alleviates Behavioral and Cognitive Symptoms Via Modulating Mitochondrial Dynamics in the A53T-α-Synuclein Mouse Model of Parkinson’s Disease
Authors: Li Huiying , Wang Hongquan , Zhang Ling , Wang Manshi , Li Yanfeng
Published: May 2021

Background

Aggregation and neurotoxicity of the presynaptic protein α-synuclein and the progressive loss of nigral dopaminergic neurons are believed to be the key hallmarks of Parkinson’s disease (PD). A53T mutant α-synuclein causes early onset PD and more severe manifestations. A growing body of evidence shows that misfolding or deposition of α-synuclein is linked to the maintenance of mitochondrial dynamics, which has been proven to play an important role in the pathogenesis of PD. It has been observed that Dl-3-n-butylphthalide (NBP) may be safe and effective in improving the non-tremor-dominant PD. However, the potential mechanism remains unclear. This study aimed to investigate whether NBP could decrease the loss of dopaminergic neurons and α-synuclein deposition and explore its possible neuroprotective mechanisms.

Methods

A total of 20 twelve-month-old human A53T α-synuclein transgenic mice and 10 matched adult C57BL/6 mice were included in the study; 10 adult C57BL/6 mice were selected as the control group and administered with saline (0.2 ml daily for 14 days); 20 human A53T α-synuclein transgenic mice were randomly divided into A53T group (treated in the same manner as in the control group) and A53T + NBP group (treated with NBP 0.2 ml daily for 14 days). Several markers of mitochondrial fission and fusion and mitophagy were determined, and the behavioral, olfactory, and cognitive symptoms were assessed as well.

Results

In the present study, it was observed that the A53T-α-synuclein PD mice exhibited anxiety-like behavioral disturbance, impairment of coordination ability, memory deficits, and olfactory dysfunction, loss of dopaminergic neurons, and α-synuclein accumulation. Meanwhile, the mitofusin 1 expression was significantly decreased, and the mitochondrial number and dynamin-related protein 1, Parkin, and LC3 levels were increased. The detected levels of all markers were reversed by NBP treatment, and the mitochondrial morphology was partially recovered.

Conclusion

In the present study, a valuable neuropharmacological role of NBP has been established in the A53T-α-synuclein PD mouse model. Possible neuroprotective mechanisms might be that NBP is involved in the maintenance of mitochondrial dynamics including mitochondrial fission and fusion and clearance of damaged mitochondria. It is essential to perform further experiments to shed light on the precise mechanisms of NBP on mitochondrial homeostasis.
Spatio-Temporal Sequential Memory Model With Mini-Column Neural Network
Authors: Lan Yawen , Wang Xiaobin , Wang Yuchen
Published: May 2021

Memory is an intricate process involving various faculties of the brain and is a central component in human cognition. However, the exact mechanism that brings about memory in our brain remains elusive and the performance of the existing memory models is not satisfactory. To overcome these problems, this paper puts forward a brain-inspired spatio-temporal sequential memory model based on spiking neural networks (SNNs). Inspired by the structure of the neocortex, the proposed model is structured by many mini-columns composed of biological spiking neurons. Each mini-column represents one memory item, and the firing of different spiking neurons in the mini-column depends on the context of the previous inputs. The Spike-Timing-Dependant Plasticity (STDP) is used to update the connections between excitatory neurons and formulates association between two memory items. In addition, the inhibitory neurons are employed to prevent incorrect prediction, which contributes to improving the retrieval accuracy. Experimental results demonstrate that the proposed model can effectively store a huge number of data and accurately retrieve them when sufficient context is provided. This work not only provides a new memory model but also suggests how memory could be formulated with excitatory/inhibitory neurons, spike-based encoding, and mini-column structure.
Direct and Transcutaneous Vagus Nerve Stimulation for Treatment of Tinnitus: A Scoping Review
Authors: Yakunina Natalia , Nam Eui-Cheol
Published: May 2021

Recent animal research has shown that vagus nerve stimulation (VNS) paired with sound stimuli can induce neural plasticity in the auditory cortex in a controlled manner. VNS paired with tones excluding the tinnitus frequency eliminated physiological and behavioral characteristics of tinnitus in noise-exposed rats. Several clinical trials followed and explored the effectiveness of VNS paired with sound stimuli for alleviating tinnitus in human subjects. Transcutaneous VNS (tVNS) has received increasing attention as a non-invasive alternative approach to tinnitus treatment. Several studies have also explored tVNS alone (not paired with sound stimuli) as a potential therapy for tinnitus. In this review, we discuss existing knowledge about direct and tVNS in terms of applicability, safety, and effectiveness in diminishing tinnitus symptoms in human subjects. This review includes all existing clinical and neuroimaging studies of tVNS alone or paired with acoustic stimulation in tinnitus patients and outlines the present limitations that must be overcome to maximize the potential of (t)VNS as a therapy for tinnitus.