scholarly journals Deafferentation of Olfactory Bulb in Subjects Dying with COVID-19

Author(s):  
Cecilia Tremblay ◽  
Thomas G Beach ◽  
Anthony J Intorcia ◽  
Jessica E Walker ◽  
Richard A Arce ◽  
...  

There have been clinical descriptions of diverse neurological effects in COVID-19 disease, involving up to 36% of patients. It appears likely that most of these are not caused by viral brain invasion but by systemic accompaniments of critical illness such as coagulopathy, deleteriously upregulated immune response, autoimmune mechanisms, hypoxia or multiorgan failure. Anosmia or hyposmia is present in a majority of COVID-19 patients, and there is early and severe involvement of the nasopharyngeal mucosa and olfactory epithelium. Preliminary studies by our group have found massive gene expression changes in olfactory bulb, but the magnitude of these changes are not different between subjects with detectable versus non-detectable olfactory bulb SARS-CoV-2 RNA. As spontaneous discharge of olfactory epithelial afferents dictates intra-olfactory bulb neurophysiological activity and connectivity, we hypothesized that olfactory bulb deafferentation during COVID-19 is responsible for a large fraction of our observed olfactory bulb transcriptional changes. As the olfactory marker protein (OMP-1) is a specific marker of olfactory epithelial afferents to the olfactory bulb and is severely depleted in animal model lesions of olfactory epithelium, we quantified OMP-1-immunoreactivity in the olfactory bulb of subjects dying with or without COVID-19. Additionally, we quantified olfactory bulb tyrosine hydroxylase (TH), which is often also reduced after olfactory epithelium lesions, and SNAP-25, a pan-synaptic marker. COVID-19 cases (n = 18) were generally elderly and were not significantly different in age or gender distribution from the non-COVID-19 cases (n = 28). Both COVID-19 and non-COVID-19 cases had a wide range of neuropathological diagnoses. The area occupied by OMP-1 immunoreactivity in COVID-19 cases was significantly less, about 60% of that in control cases but amongst subjects with COVID-19, there was no significant difference between OBT-SARS-CoV-2-PCR-positive and negative cases. There were no significant group differences for TH or SNAP-25, supporting a selective effect for OMP-1. We suggest that olfactory dysfunction, and some of the COVID-19-associated transcriptional changes that we have reported for the olfactory bulb and amygdala, may be due to olfactory bulb deafferentation and subsequent transsynaptic effects. Additionally, animal models of olfactory bulb deafferentation or bulbectomy indicate a possibility for widespread changes in interconnected brain regions, providing a possible substrate for diverse post-acute COVID-19 neurological sequelae.

2019 ◽  
Vol 19 (9) ◽  
pp. 1132-1140
Author(s):  
Heba A.E. Mohamed ◽  
Hossa F. Al-Shareef

Background: Quinolones are a significant group of nitrogen heterocyclic compounds that exist in therapeutic agents, alkaloids, and synthetic small molecules that have important biological activities. A wide range of quinolones have been used as antituberculosis, antibacterial, anti-malarial, antifungal, anticonvulsant, anticancer agents and urease inhibitors. Methods: Ethyl 3,3-disubstituted-2-cyano propionates containing hybride quinolones derivatives were synthesized by the reaction of 1-amino-7-hydroxy-4-methylquinolin-2(1H)-one and its dibromo derivative with α, β-unsaturated carbonyl in ethanol. Results: A novel series of hybrid 2-quinolone derivatives was designed and synthesized. The compounds structures were confirmed using different spectroscopic methods and elemental analysis. The cytotoxic activities of all the compounds were assessed against HepG2 cell line in comparison with doxorubicin as a standard drug. Conclusion: Most compounds revealed superior anti-proliferative activity than the standard. Compound 4b, is the most active compound (IC50 = 0.39mM) compared with doxorubicin (IC50 = 9.23mM). DNA flow cytometric analysis of compound 4b showed cell cycle arrest at G2/M phase with a concomitant increase of cells in apoptotic phase. Dual annexin-V/ propidium iodide staining assay of compound 4b revealed that the selected candidate increased the apoptosis of HepG-2 cells more than control.


2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Bingran Wang ◽  
Tiancheng Lou ◽  
Lingling Wei ◽  
Wenchan Chen ◽  
Longbing Huang ◽  
...  

AbstractAlternaria alternata, a causal agent of leaf blights and spots on a wide range of hosts, has a high risk of developing resistance to fungicides. Procymidone, a dicarboximide fungicide (DCF), has been widely used in controlling Alternaria leaf blights in China for decades. However, the resistance of A. alternata against DCFs has rarely been reported from crucifer plants. A total of 198 A. alternata isolates were collected from commercial fields of broccoli and cabbage during 2018–2019, and their sensitivities to procymidone were determined. Biochemical and molecular characteristics were subsequently compared between the high-level procymidone-resistant (ProHR) and procymidone-sensitive (ProS) isolates, and also between ProHR isolates from broccoli and cabbage. Compared with ProS isolates, the mycelial growth rate, sporulation capacity and virulence of most ProHR isolates were reduced; ProHR isolates displayed an increased sensitivity to osmotic stresses and a reduced sensitivity to sodium dodecyl sulfate (SDS); all ProHR isolates showed a reduced sensitivity to hydrogen peroxide (H2O2) except for the isolate B102. Correlation analysis revealed a positive cross-resistance between procymidone and iprodione, or fludioxonil. When treated with 10 μg/mL of procymidone, both mycelial intracellular glycerol accumulations (MIGAs) and relative expression of AaHK1 in ProS isolates were higher than those in ProHR isolates. Sequence alignment of AaHK1 from ten ProHR isolates demonstrated that five of them possessed a single-point mutation (P94A, V612L, E708K or Q924STOP), and four isolates had an insertion or a deletion in their coding regions. No significant difference in biochemical characteristics was observed among ProHR isolates from two different hosts, though mutations in AaHK1 of the cabbage-originated ProHR isolates were distinct from those of the broccoli-originated ProHR isolates.


2021 ◽  
Vol 9 (4) ◽  
pp. 839
Author(s):  
Muhammad Rafiullah Khan ◽  
Vanee Chonhenchob ◽  
Chongxing Huang ◽  
Panitee Suwanamornlert

Microorganisms causing anthracnose diseases have a medium to a high level of resistance to the existing fungicides. This study aimed to investigate neem plant extract (propyl disulfide, PD) as an alternative to the current fungicides against mango’s anthracnose. Microorganisms were isolated from decayed mango and identified as Colletotrichum gloeosporioides and Colletotrichum acutatum. Next, a pathogenicity test was conducted and after fulfilling Koch’s postulates, fungi were reisolated from these symptomatic fruits and we thus obtained pure cultures. Then, different concentrations of PD were used against these fungi in vapor and agar diffusion assays. Ethanol and distilled water were served as control treatments. PD significantly (p ≤ 0.05) inhibited more of the mycelial growth of these fungi than both controls. The antifungal activity of PD increased with increasing concentrations. The vapor diffusion assay was more effective in inhibiting the mycelial growth of these fungi than the agar diffusion assay. A good fit (R2, 0.950) of the experimental data in the Gompertz growth model and a significant difference in the model parameters, i.e., lag phase (λ), stationary phase (A) and mycelial growth rate, further showed the antifungal efficacy of PD. Therefore, PD could be the best antimicrobial compound against a wide range of microorganisms.


2015 ◽  
Vol 112 (41) ◽  
pp. 12846-12851 ◽  
Author(s):  
Filomene G. Morrison ◽  
Brian G. Dias ◽  
Kerry J. Ressler

Although much work has investigated the contribution of brain regions such as the amygdala, hippocampus, and prefrontal cortex to the processing of fear learning and memory, fewer studies have examined the role of sensory systems, in particular the olfactory system, in the detection and perception of cues involved in learning and memory. The primary sensory receptive field maps of the olfactory system are exquisitely organized and respond dynamically to cues in the environment, remaining plastic from development through adulthood. We have previously demonstrated that olfactory fear conditioning leads to increased odorant-specific receptor representation in the main olfactory epithelium and in glomeruli within the olfactory bulb. We now demonstrate that olfactory extinction training specific to the conditioned odor stimulus reverses the conditioning-associated freezing behavior and odor learning-induced structural changes in the olfactory epithelium and olfactory bulb in an odorant ligand-specific manner. These data suggest that learning-induced freezing behavior, structural alterations, and enhanced neural sensory representation can be reversed in adult mice following extinction training.


Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3497
Author(s):  
Piotr Stachak ◽  
Izabela Łukaszewska ◽  
Edyta Hebda ◽  
Krzysztof Pielichowski

Polyurethanes (PUs) are a significant group of polymeric materials that, due to their outstanding mechanical, chemical, and physical properties, are used in a wide range of applications. Conventionally, PUs are obtained in polyaddition reactions between diisocyanates and polyols. Due to the toxicity of isocyanate raw materials and their synthesis method utilizing phosgene, new cleaner synthetic routes for polyurethanes without using isocyanates have attracted increasing attention in recent years. Among different attempts to replace the conventional process, polyaddition of cyclic carbonates (CCs) and polyfunctional amines seems to be the most promising way to obtain non-isocyanate polyurethanes (NIPUs) or, more precisely, polyhydroxyurethanes (PHUs), while primary and secondary –OH groups are being formed alongside urethane linkages. Such an approach eliminates hazardous chemical compounds from the synthesis and leads to the fabrication of polymeric materials with unique and tunable properties. The main advantages include better chemical, mechanical, and thermal resistance, and the process itself is invulnerable to moisture, which is an essential technological feature. NIPUs can be modified via copolymerization or used as matrices to fabricate polymer composites with different additives, similar to their conventional counterparts. Hence, non-isocyanate polyurethanes are a new class of environmentally friendly polymeric materials. Many papers on the matter above have been published, including both original research and extensive reviews. However, they do not provide collected information on NIPU composites fabrication and processing. Hence, this review describes the latest progress in non-isocyanate polyurethane synthesis, modification, and finally processing. While focusing primarily on the carbonate/amine route, methods of obtaining NIPU are described, and their properties are presented. Ways of incorporating various compounds into NIPU matrices are characterized by the role of PHU materials in copolymeric materials or as an additive. Finally, diverse processing methods of non-isocyanate polyurethanes are presented, including electrospinning or 3D printing.


2019 ◽  
Vol 11 (8) ◽  
pp. 2400 ◽  
Author(s):  
Karthikeyan Mariappan ◽  
Deyi Zhou

Agriculture is the main sources of income for humans. Likewise, agriculture is the backbone of the Indian economy. In India, Tamil Nadu regional state has a wide range of possibilities to produce all varieties of organic products due to its diverse agro-climatic condition. This research aimed to identify the economics and efficiency of organic farming, and the possibilities to reduce farmers’ suicides in the Tamil Nadu region through the organic agriculture concept. The emphasis was on farmers, producers, researchers, and marketers entering the sustainable economy through organic farming by reducing input cost and high profit in cultivation. A survey was conducted to gather data. One way analysis of variance (ANOVA) has been used to test the hypothesis regards the cost and profit of rice production. The results showed that there was a significant difference in profitability between organic and conventional farming methods. It is very transparent that organic farming is the leading concept of sustainable agricultural development with better organic manures that can improve soil fertility, better yield, less input cost and better return than conventional farming. The study suggests that by reducing the cost of cultivation and get a marginal return through organic farming method to poor and small scale farmers will reduce socio-economic problems such as farmers’ suicides in the future of Indian agriculture.


Author(s):  
Roman Rotermund ◽  
Jan Regelsberger ◽  
Katharina Osterhage ◽  
Jens Aberle ◽  
Jörg Flitsch

Abstract Background In previous reports on experiences with an exoscope, this new technology was not found to be applicable for transsphenoidal pituitary surgery. As a specialized center for pituitary surgery, we were using a 4K 3D video microscope (Orbeye, Olympus) to evaluate the system for its use in transsphenoidal pituitary surgery in comparison to conventional microscopy. Method We report on 296 cases performed with the Orbeye at a single institution. An observational study was conducted with standardized subjective evaluation by the surgeons after each procedure. An objective measurement was added to compare the exoscopic and microscopic methods, involving surgery time and the initial postoperative remission rate in matched cohorts. Results The patients presented with a wide range of pathologies. No serious events or minor complications occurred based on the usage of the 4K 3D exoscope. There was no need for switching back to the microscope in any of the cases. Compared to our microsurgically operated collective, there was no significant difference regarding duration of surgery, complications, or extent of resection. The surgeons rated the Orbeye beneficial in regard to instrument size, positioning, surgeon’s ergonomics, learning curve, image resolution, and high magnification. Conclusions The Orbeye exoscope presents with optical and digital zoom options as well as a 4K image resolution and 3D visualization resulting in better depth perception and flexibility in comparison to the microscope. Split screen mode offers the complementary benefit of the endoscope which may increase the possibilities of lateral view but has to be evaluated in comparison to endoscopic transsphenoidal procedures in the next step.


1978 ◽  
Vol 279 (1) ◽  
pp. 605-619 ◽  
Author(s):  
H Arito ◽  
M Iino ◽  
S F Takagi

Author(s):  
R. Fekete ◽  
Gy. Haszonits ◽  
D. Schmidt ◽  
H. Bak ◽  
O. Vincze ◽  
...  

AbstractThe spread of alien species with the expansion of road networks and increasing traffic is a well-known phenomenon globally. Besides their corridor effects, road maintenance practices, such as the use of de-icing salts during winter facilitate the spread of halophyte (salt tolerant) species along roads. A good example is Plantago coronopus, a mainly coastal halophyte which has started spreading inland from the Atlantic and Mediterranean coastal habitats, recently reaching even Central European countries (e.g. Hungary). Here we studied the spread of this halophyte and tried to identify factors explaining its successful dispersion along roads, while also comparing native and non-native roadside occurrences with regard to altitude of the localities, size of roadside populations and frequency of roadside occurrences. We completed a comprehensive literature review and collected more than 200 reports of occurrence from roadsides spanning a total of 38 years. During systematic sampling the frequency of the species along roads was significantly higher in the Mediterranean (native area), than along Hungarian (non-native area) roads, however the average number of individuals at the sampling localities were very similar, and no significant difference could be detected. Using a germination experiment, we demonstrate that although the species is able to germinate even at high salt concentrations, salt is not required for germination. Indeed salt significantly decreases germination probability of the seeds. The successful spread of the species could most likely be explained by its remarkably high seed production, or some special characteristics (e.g. seed dimorphism) and its ability to adapt to a wide range of environmental conditions. Considering the recent and rapid eastward spread of P. coronopus, occurrences in other countries where it has not been reported yet can be predicted in coming years.


2015 ◽  
Vol 15 (10) ◽  
pp. 5429-5442 ◽  
Author(s):  
E. Giannakaki ◽  
A. Pfüller ◽  
K. Korhonen ◽  
T. Mielonen ◽  
L. Laakso ◽  
...  

Abstract. Raman lidar data obtained over a 1 year period has been analysed in relation to aerosol layers in the free troposphere over the Highveld in South Africa. In total, 375 layers were observed above the boundary layer during the period 30 January 2010 to 31 January 2011. The seasonal behaviour of aerosol layer geometrical characteristics, as well as intensive and extensive optical properties were studied. The highest centre heights of free-tropospheric layers were observed during the South African spring (2520 ± 970 m a.g.l., also elsewhere). The geometrical layer depth was found to be maximum during spring, while it did not show any significant difference for the rest of the seasons. The variability of the analysed intensive and extensive optical properties was high during all seasons. Layers were observed at a mean centre height of 2100 ± 1000 m with an average lidar ratio of 67 ± 25 sr (mean value with 1 standard deviation) at 355 nm and a mean extinction-related Ångström exponent of 1.9 ± 0.8 between 355 and 532 nm during the period under study. Except for the intensive biomass burning period from August to October, the lidar ratios and Ångström exponents are within the range of previous observations for urban/industrial aerosols. During Southern Hemispheric spring, the biomass burning activity is clearly reflected in the optical properties of the observed free-tropospheric layers. Specifically, lidar ratios at 355 nm were 89 ± 21, 57 ± 20, 59 ± 22 and 65 ± 23 sr during spring (September–November), summer (December–February), autumn (March–May) and winter (June–August), respectively. The extinction-related Ångström exponents between 355 and 532 nm measured during spring, summer, autumn and winter were 1.8 ± 0.6, 2.4 ± 0.9, 1.8 ± 0.9 and 1.8 ± 0.6, respectively. The mean columnar aerosol optical depth (AOD) obtained from lidar measurements was found to be 0.46 ± 0.35 at 355 nm and 0.25 ± 0.2 at 532 nm. The contribution of free-tropospheric aerosols on the AOD had a wide range of values with a mean contribution of 46%.


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