Dissipation kinetics and risk assessment of residues of combination product of two fungicides, fluxapyroxad, and pyraclostrobin in cumin.

Supervised field trial studies were conducted to understand dissipation kinetics and harvest time residues of a combination product of fluxapyroxad and pyraclostrobin in cumin plant/leaves and seeds at different locations in India. The results showed initial accumulation of fluxapyroxad at the levels of 15.4 and 20.2 mg kg-1 and pyraclostrobin at the level of 21.2 and 33.4 mg kg-1 in cumin leaves/plant in Anand, Gujarat. Fluxapyroxad and pyraclostrobin followed zero-order and first-order dissipation kinetics in cumin plant/leaves samples respectively. The residues translocated to cumin seeds. As the hazard quotient (HQ) was <1 in all cases consumer health risk may be negligible.

Dissipation and dietary risk assessment of fluoxapiprolin (and its metabolites) residues in cucumber and tomato samples under field conditions.

The present study was undertaken to understand the dissipation behaviour/kinetics of fluoxapiprolin and its metabolites in cucumber and tomato under field conditions. A QuEChERS based extraction method followed by liquid chromatography coupled to mass spectrometry (LC-MS/MS) analysis showed that all method validation parameters were within the acceptable range as per international standards with a limit of quantitation (LOQ) of 0.01 mg kg-1 for all analytes. As significant matrix effects were observed with a few metabolites, matrix matched standards were used for the whole study. Residues of fluoxapiprolin in cucumber at standard dose were steady from 0 to 3 day after application and were below LOQ on the 5th day after application. In cucumber fruit at double dose and in tomato at both the doses the residues followed second-order kinetics and were respectively ≤ LOQ from days 7 and 14 onwards. Pre-harvest intervals (PHI) of 5 days and 14 days are proposed for cucumber and tomato fruits respectively. All the metabolites were ≤ LOQ from day 0 in all the matrices. The consumer risk, assessed as Hazard Quotient (HQ), showed that HQ was ≤1 in all the cases. The results of the present study and earlier studies on other similar fungicides suggest that the use of fluoxapiprolin in cucumber and tomato fruits may not pose health or environmental hazards provided that good agricultural practices are followed and the proposed waiting period is observed. The data from the present study can be used by regulatory bodies in establishing maximum residue limits.

Dissipation and evaluation of different treatments on the residues of different insecticides in/on cauliflower curd.

A field study to understand dissipation rates and effect of various washing treatments on the residues of seven different insecticides, i.e. tetraniliprole 200 SC, emamectin benzoate 5 SG, lufenuron 5.4 EC, indoxacarb 14.5 SC, thiodicarb 75 WP, profenofos 50 EC and cypermethrin 25 EC in/on cauliflower curd has been conducted. The results showed that initial deposits (just after the last insecticide application, i.e. 0 d) of tetraniliprole, emamectin benzoate, lufenuron, indoxacarb, thiodicarb, profenofos and cypermethrin were 0.43, 0.03, 0.25, 0.28, 0.38, 6.70 and 0.68 mg kg-1, respectively. The dissipation pattern of all the tested insecticides followed monophasic, first order kinetics with the half-lives of 6.25, 8.85, 3.27, 7.71, 4.36, 2.98 and 3.76 d, respectively. Proposed pre-harvest intervals for these insecticides are 6, 9, 3, 8, 4, 3 and 4 d, respectively. All the decontamination techniques showed reductions in residue levels. However, treatment by soaking in 5% sodium bicarbonate aqueous solution showed 54%, 42%, 53%, 48%, 22%, 54% and 77% maximum reductions in residues of tetraniliprole, emamectin benzoate, lufenuron, indoxacarb, profenofos and cypermethrin, respectively, in cauliflower curds. The next best treatment was soaking cauliflower curds in water at 45-50 °C for 10 min, which reduced the residues of cypermethrin, profenofos, tetraniliprole, thiodicarb, emamectin benzoate and lufenuron.

Analysis, residue behaviour and risk assessment of combination product of iprovalicarb + copper oxychloride in representative fruiting vegetables, cucurbit and in soil using LC-MS/MS and ICP-MS.

Combination product of two herbicides, i.e. iprovalicarb and copper oxychloride, is a new formulation. There is paucity of data on the dissipation pattern and risk assessment of this combination product in crops. To understand the dissipation behaviour/kinetics of this product, a supervised field trial was undertaken on cucumber and tomato. Method validation for a QuEChERS-based method for analysis of these pesticides from cucumber and tomato matrices reveals that all the parameters were within the acceptance range in accordance with SANTE. The limit of quantitation (LOQ) for iprovalicarb in cucumber and tomato fruits, and in soil matrices when analysed on LC-MS/MS was established at 0.01 mg kg-1. Similarly, the LOQ for copper oxychloride (as copper) on ICP-MS was established at 0.5 mg kg-1 in cucumber and tomato fruits and 5.0 mg kg-1 in soil. Dissipation of iprovalicarb was slower in tomato fruits as compared to cucumber fruits. The initial accumulation of the residues of iprovalicarb was 0.073 and 0.243 mg kg-1 in cucumber and 0.214 and 0.432 mg kg-1 in tomato fruits at standard and double dose, respectively. Similarly, copper oxychloride residues were 3.51 and 6.45 mg kg-1 in cucumber and 1.26 and 2.56 mg kg-1 in tomato fruits at standard and double dose, respectively. The residues were below LOQ in cucumber fruits, tomato fruits and soil at the time of harvest. The residues of copper oxychloride persisted till harvest time in cucumber fruits and in soil. A preharvest interval (PHI) of 3 day is recommended on safer side for the combination product of iprovalicarb + copper oxychloride. Theoretical maximum daily intake (TMDI) is less than maximum permissible intake (MPI) for iprovalicarb and copper oxychloride at both the doses from 0 day and onward. The results from the present study can be of immense importance for establishing label claims, maximum residue limits (MRLs) and risk assessment by national and international regulatory agencies.

Phase Aberration Correction for In Vivo Ultrasound Localization Microscopy Using a Spatiotemporal Complex-Valued Neural Network.

Ultrasound Localization Microscopy (ULM) can map microvessels at a resolution of a few micrometers ( [Formula: see text]). Transcranial ULM remains challenging in presence of aberrations caused by the skull, which lead to localization errors. Herein, we propose a deep learning approach based on recently introduced complex-valued convolutional neural networks (CV-CNNs) to retrieve the aberration function, which can then be used to form enhanced images using standard delay-and-sum beamforming. CV-CNNs were selected as they can apply time delays through multiplication with in-phase quadrature input data. Predicting the aberration function rather than corrected images also confers enhanced explainability to the network. In addition, 3D spatiotemporal convolutions were used for the network to leverage entire microbubble tracks. For training and validation, we used an anatomically and hemodynamically realistic mouse brain microvascular network model to simulate the flow of microbubbles in presence of aberration. The proposed CV-CNN performance was compared to the coherence-based method by using microbubble tracks. We then confirmed the capability of the proposed network to generalize to transcranial in vivo data in the mouse brain (n=3). Vascular reconstructions using a locally predicted aberration function included additional and sharper vessels. The CV-CNN was more robust than the coherence-based method and could perform aberration correction in a 6-month-old mouse. After correction, we measured a resolution of [Formula: see text] for younger mice, representing an improvement of 25.8%, while the resolution was improved by 13.9% for the 6-month-old mouse. This work leads to different applications for complex-valued convolutions in biomedical imaging and strategies to perform transcranial ULM.

Exploring Optically Stable Reddish-Orange Fluorescent Magnetic Pigment (0.90)Y2O3:(0.10-x)Eu3+:(x)Bi3+ for Anti-counterfeiting Applications.

The (0.90)Y2O3:(0.10-x)Eu3+:(x)Bi3+ nanophosphors (0.00 ≤ x ≤ 0.06) are synthesised using chemical combustion citrate route and characterized via X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, UV- visible and photoluminescence spectroscopy. The scanning electron micrographs indicate that the grain size of the phosphors ranges between 40 to 50 nm. The photoluminescence (PL) spectra, acquired under the excitation wavelength of 365 nm of ultraviolet light, show emission peaks at wavelengths 580 nm, 586-598 nm, 610 nm, 629-661 nm and 686-695 nm corresponding to the 5D0 → 7FJ electronic transitions of the Eu3+ ion with J = 0, 1, 2, 3 and 4, respectively. The most intense PL spectra at 611 nm (5D0 → 7F2), showcasing reddish-orange emission, indicate a higher concentration of Eu3+ ions in asymmetric sites within the Y2O3 host matrix. The presence of the distinct electronic transitions of Eu3+ in PL spectra acclaims that Bi3+ ions transfer their energy efficiently to Eu3+ ions in the matrix. Physical and chemical tests are being conducted on nanophosphors with Bi3+ substitutional doping of x = 0.02 and x = 0.04, both demonstrating intense PL emission. Magnetisation measurements suggest the soft magnetic nature of the nanophosphors, attributing it to the presence of Eu3+ ions in the 7F2 state. The highest PL intensity is seen in the nanophosphor (x = 0.04) with substitutional doping of 6% of Eu3+ and 4% of Bi3+ in Y2O3. This nanophosphor also demonstrates excellent optical stability in the investigated conditions and exhibits soft magnetic behaviour, positioning it as a promising material for incorporation as a fluorescent magnetic pigment in security ink applications. These features serve to prevent counterfeiting of secured documents both optically and magnetically.

Pannexin-1 opening in neuronal edema causes cell death but also leads to protection via increased microglia contacts.

Neuronal swelling during cytotoxic edema is triggered by Na+ and Cl- entry and is Ca2+ independent. However, the causes of neuronal death during swelling are unknown. Here, we investigate the role of large-conductance Pannexin-1 (Panx1) channels in neuronal death during cytotoxic edema. Panx1 channel inhibitors reduce and delay neuronal death in swelling triggered by voltage-gated Na+ entry with veratridine. Neuronal swelling causes downstream production of reactive oxygen species (ROS) that opens Panx1 channels. We confirm that ROS activates Panx1 currents with whole-cell electrophysiology and find scavenging ROS is neuroprotective. Panx1 opening and subsequent ATP release attract microglial processes to contact swelling neurons. Depleting microglia using the CSF1 receptor antagonist PLX3397 or blocking P2Y12 receptors exacerbates neuronal death, suggesting that the Panx1-ATP-dependent microglia contacts are neuroprotective. We conclude that cytotoxic edema triggers oxidative stress in neurons that opens Panx1 to trigger death but also initiates neuroprotective feedback mediated by microglia contacts.

Method validation, dissipation and residue status of fluopicolide and fosetyl-aluminium in citrus using a rapid extraction method coupled with ultra-performance liquid chromatography-tandem mass spectrometry.

The dissipation and residue status of a combination of fluopicolide and fosetyl-aluminium (fosetyl-Al) in citrus were evaluated in an experimental field. An efficient and sensitive liquid chromatography-tandem mass spectrometry, with rapid extraction, was carried out according to the SANTE guidelines. During the method validation, the recovery was within the range of 106.1-117.5, 94.4-115 and 85.4-109.5%, for fluopicolide, its metabolite 2,6-dichlorobenzamide and fosetyl-Al, respectively, with a relative standard deviation (RSD) of 0.3-10.6%. As a result, accuracy and precision at the spiking concentrations of 0.01, 0.05 and 0.10 mg/kg in citrus were within the acceptable range of 70-120% with an RSD of 20%. The amount of the deposits of fluopicolide, 2,6-dichlorobenzamide and fosetyl-Al was less than the limit of quantification (LOQ) at 0.01 mg/kg at 0 day, adhering to the application in standard [1.77 + 2.66 g of active ingredient (a.i.)/L] and double (3.54 + 5.32 g a.i./L) doses. The present study proposes that the utilisation of fluopicolide and fosetyl-Al in citrus and the soil may not pose a health or environmental hazard provided that good agricultural practices are followed.

Orai, RyR, and IP3R channels cooperatively regulate calcium signaling in brain mid-capillary pericytes.

Pericytes are multifunctional cells of the vasculature that are vital to brain homeostasis, yet many of their fundamental physiological properties, such as Ca2+ signaling pathways, remain unexplored. We performed pharmacological and ion substitution experiments to investigate the mechanisms underlying pericyte Ca2+ signaling in acute cortical brain slices of PDGFRß-Cre::GCaMP6f mice. We report that mid-capillary pericyte Ca2+ signalling differs from ensheathing type pericytes in that it is largely independent of L- and T-type voltage-gated calcium channels. Instead, Ca2+ signals in mid-capillary pericytes were inhibited by multiple Orai channel blockers, which also inhibited Ca2+ entry triggered by endoplasmic reticulum (ER) store depletion. An investigation into store release pathways indicated that Ca2+ transients in mid-capillary pericytes occur through a combination of IP3R and RyR activation, and that Orai store-operated calcium entry (SOCE) is required to sustain and amplify intracellular Ca2+ increases evoked by the GqGPCR agonist endothelin-1. These results suggest that Ca2+ influx via Orai channels reciprocally regulates IP3R and RyR release pathways in the ER, which together generate spontaneous Ca2+ transients and amplify Gq-coupled Ca2+ elevations in mid-capillary pericytes. Thus, SOCE is a major regulator of pericyte Ca2+ and a target for manipulating their function in health and disease.

Dissipation kinetics of co-formulation with two herbicides, clodinafop-propargyl and oxyfluorfen, in/on onion (Allium cepa) samples.

Supervised field trail on dissipation of co-formulation with herbicides clodinafop-propargyl and oxyfluorfen in spring onion showed similar pattern of dissipation during two different seasons. Residues of clodinafop-propargyl reached ≤ limit of quantitation (LOQ, 0.05 mg kg-1) on 3rd day after application at both standard and double dose during both the seasons. Oxyfluorfen residues followed first-order kinetics in both the doses during first season with half-life of 0.81 to 3.14 days. The residues of clodinafop-propargyl were detected in soil at both the doses during first season. However, residues were ≤ LOQ (0.05 mg kg-1) during second season. The residues of oxyfluorfen were detected only in double dose during first season in soil. In all other cases and in onion bulb, residues were ≤ LOQ (0.05 mg kg-1) at the time of harvest. As the residues were either ≤ LOQ (0.05 mg kg-1) on 3rd day or have a half-life of 3.14 days, the co-formulation can be used safely, provided a pre harvest interval (PHI) of 3 days is followed. On the basis of maximum residue limits (MRLs) in other commodities and from the data of present study, a default MRL of 0.05 mg kg-1 is proposed for both the pesticides.

Analytical method development, validation and study on behaviour of ipfencarbazone in paddy (rice).

Supervised field trial was conducted to study persistence of a pre-emergent herbicide, ipfencarbazone (25% SC) on rice crop. Single application of two different doses, 156.25 g a.i.ha-1/625 mL formulationha-1 and 312.50 g a.i.ha-1/1250 mL formulationha-1, was applied. Method was validated to analyse ipfencarbazone in rice samples (leaf/plant, grain, straw and husk) and in soil. Initial accumulation of ipfencarbazone in rice plants was 6.72 and 14.71 mg kg-1 in standard and double dose, respectively. The residues decreased linearly with r2 values of 0.92 and 0.98 in different doses and reached below limit of quantitation (LOQ) of 0.01 µg kg-1 (for rice plant/leaf) and 0.05 µg kg-1 (for rice grain, husk, straw) on 30th and 97th (harvest) day respectively after application in both the doses. An average half-life of ipfencarbazone was approximately 4 days. Less than LOQ levels at harvest and short half-life suggest that the use of ipfencarbazone is safe, provided good agricultural practices (GAP) are followed. The data can be used by regulatory authorities like Food Safety and Standards Authority of India (FSSAI) and CODEX for establishing maximum residue limits (MRLs) of ipfencarbazone.

Effect of neuroanatomy on corticomotor excitability during and after transcranial magnetic stimulation and intermittent theta burst stimulation.

Individual neuroanatomy can influence motor responses to transcranial magnetic stimulation (TMS) and corticomotor excitability after intermittent theta burst stimulation (iTBS). The purpose of this study was to examine the relationship between individual neuroanatomy and both TMS response measured using resting motor threshold (RMT) and iTBS measured using motor evoked potentials (MEPs) targeting the biceps brachii and first dorsal interosseus (FDI). Ten nonimpaired individuals completed sham-controlled iTBS sessions and underwent MRI, from which anatomically accurate head models were generated. Neuroanatomical parameters established through fiber tractography were fiber tract surface area (FTSA), tract fiber count (TFC), and brain scalp distance (BSD) at the point of stimulation. Cortical magnetic field induced electric field strength (EFS) was obtained using finite element simulations. A linear mixed effects model was used to assess effects of these parameters on RMT and iTBS (post-iTBS MEPs). FDI RMT was dependent on interactions between EFS and both FTSA and TFC. Biceps RMT was dependent on interactions between EFS and and both FTSA and BSD. There was no groupwide effect of iTBS on the FDI but individual changes in corticomotor excitability scaled with RMT, EFS, BSD, and FTSA. iTBS targeting the biceps was facilitatory, and dependent on FTSA and TFC. MRI-based measures of neuroanatomy highlight how individual anatomy affects motor system responses to different TMS paradigms and may be useful for selecting appropriate motor targets when designing TMS based therapies.

Randomized trial of rTMS in traumatic brain injury: improved subjective neurobehavioral symptoms and increases in EEG delta activity.

PRIMARY OBJECTIVE: While repetitive transcranial magnetic stimulation (rTMS) has shown efficacy for cognitive difficulties accompanying depression, it is unknown if it can improve cognition in persons with traumatic brain injury. RESEARCH DESIGN: Using a sham-controlled crossover design, we tested the capacity of high frequency rTMS of the prefrontal cortex to improve neuropsychological performance in attention, learning and memory, and executive function. METHODS: Twenty-six participants with cognitive complaints and a history of mild-to-moderate traumatic brain injury were randomly assigned to receive first either active or sham 10 Hz stimulation for 20 minutes (1200 pulses) per session for five consecutive days. After a one-week washout, the other condition (active or sham) was applied. Pre- and post-treatment measures included neuropsychological tests, cognitive and emotional symptoms, and EEG. MAIN OUTCOMES AND RESULTS: Results indicated no effect of treatment on cognitive function. Subjective measures of depression, sleep dysfunction, post-concussive symptoms (PCS), and executive function showed significant improvement with stimulation, retaining improved levels at two-week follow-up. EEG delta power exhibited elevation one week after stimulation cessation. CONCLUSIONS: While there is no indication that rTMS is beneficial for neuropsychological performance, it may improve PCS and subjective cognitive dysfunction. Long-term alterations in cortical oscillations may underlie the therapeutic effects of rTMS.

Development, validation and evaluation of matrix effect of a QuEChERS-based multiresidue method with low temperature dispersive clean-up for analysis of 104 pesticides in cumin (Cuminum cyminum) by LC-MS/MS.

BACKGROUND: Until now, there is no method available for analysis of pesticide residues in complex matrices like spices. Therefore, there is an urgent need to develop and validate a QuEChERS-based method for the estimation of 104 pesticides in cumin seed. RESULTS: Samples were spiked for 109 pesticides at concentrations of 0.1, 0.5 and 1.0 mg kg-1 . Of these 104 pesticides were recovered. At 0.1, 0.5 and 0.1 mg kg-1 , recoveries ranged from 71% to 108% when compared with matrix matched standards. Seventeen pesticides showed higher or lower recoveries than acceptable range (70-120%) when quantified using solvent standards showing significant matrix effect (ME) (≥ ±20%) even after 20× dilution. However, for the other pesticides ME was significantly eliminated on dilution. The recovery percentage improved for all pesticides on quantitation with matrix matched standards when compared with solvent standards. For pesticides with lower European Union (EU) maximum residue limits (MRLs), an experiment at lower spiking concentrations of 0.01 and 0.05 mg kg-1 with lower dilutions (8×) reveals that almost all pesticides with lower EU MRLs (0.02 and 0.05 mg kg-1 ) showed recoveries in the range 74-124% and relative standard deviation (RSD) less than 20%. CONCLUSION: Theoretical limit of quantitation (LOQ) is proposed which ranged from 0.01 to 0.18 mg kg-1 for matrix matched standards. An LOQ of 0.01 mg kg-1 was easily achieved for the pesticides with lower EU MRLs with lower dilutions (8×) with exception of fipronil for which this can be achieved without dilution provided matrix matched standards are used. The method can be extended to other spices. © 2021 Society of Chemical Industry.

Diversity of neurovascular coupling dynamics along vascular arbors in layer II/III somatosensory cortex.

The spatial-temporal sequence of cerebral blood flow (CBF), cerebral blood volume (CBV) and blood velocity changes triggered by neuronal activation is critical for understanding functional brain imaging. This sequence follows a stereotypic pattern of changes across different zones of the vasculature in the olfactory bulb, the first relay of olfaction. However, in the cerebral cortex, where most human brain mapping studies are performed, the timing of activity evoked vascular events remains controversial. Here we utilized a single whisker stimulation model to map out functional hyperemia along vascular arbours from layer II/III to the surface of primary somatosensory cortex, in anesthetized and awake Thy1-GCaMP6 mice. We demonstrate that sensory stimulation triggers an increase in blood velocity within the mid-capillary bed and a dilation of upstream large capillaries, and the penetrating and pial arterioles. We report that under physiological stimulation, response onset times are highly variable across compartments of different vascular arbours. Furthermore, generating transfer functions (TFs) between neuronal Ca2+ and vascular dynamics across different brain states demonstrates that anesthesia decelerates neurovascular coupling (NVC). This spatial-temporal pattern of vascular events demonstrates functional diversity not only between different brain regions but also at the level of different vascular arbours within supragranular layers of the cerebral cortex.

Transfer functions linking neural calcium to single voxel functional ultrasound signal.

Functional ultrasound imaging (fUS) is an emerging technique that detects changes of cerebral blood volume triggered by brain activation. Here, we investigate the extent to which fUS faithfully reports local neuronal activation by combining fUS and two-photon microscopy (2PM) in a co-registered single voxel brain volume. Using a machine-learning approach, we compute and validate transfer functions between dendritic calcium signals of specific neurons and vascular signals measured at both microscopic (2PM) and mesoscopic (fUS) levels. We find that transfer functions are robust across a wide range of stimulation paradigms and animals, and reveal a second vascular component of neurovascular coupling upon very strong stimulation. We propose that transfer functions can be considered as reliable quantitative reporters to follow neurovascular coupling dynamics.

Safety Study of Combination Treatment: Deep Brain Stimulation and Transcranial Magnetic Stimulation.

Patients with advanced Parkinson's disease (PD) often receive deep brain stimulation (DBS) treatment, in which conductive leads are surgically implanted in the brain. While DBS treats tremor and rigidity, patients often continue to suffer from speech and swallowing impairments. There is preliminary evidence that transcranial magnetic stimulation (TMS) of the cortex may be beneficial for these symptoms. However, the potential electromagnetic interactions of the strong magnetic fields from TMS on the conductive leads is unknown, and the combination therapy has not been approved for use. In this article, we report an experimental study of the safety of combining DBS and TMS. We fabricated an anatomically accurate head and brain phantom with electrical conductivities matching cerebrospinal fluid and averaged conductivity of gray and white matter. Induced current on an implanted DBS probe in the brain phantom was measured. Our results show that TMS will induce current values in the range or higher than typical DBS stimulation current. Thus, the combination of TMS/DBS treatment might cause over-stimulation in the brain when stimulated directly over the DBS lead with 100% TMS current intensity.

Perivascular spaces in the brain: anatomy, physiology and pathology.

Perivascular spaces include a variety of passageways around arterioles, capillaries and venules in the brain, along which a range of substances can move. Although perivascular spaces were first identified over 150 years ago, they have come to prominence recently owing to advances in knowledge of their roles in clearance of interstitial fluid and waste from the brain, particularly during sleep, and in the pathogenesis of small vessel disease, Alzheimer disease and other neurodegenerative and inflammatory disorders. Experimental advances have facilitated in vivo studies of perivascular space function in intact rodent models during wakefulness and sleep, and MRI in humans has enabled perivascular space morphology to be related to cognitive function, vascular risk factors, vascular and neurodegenerative brain lesions, sleep patterns and cerebral haemodynamics. Many questions about perivascular spaces remain, but what is now clear is that normal perivascular space function is important for maintaining brain health. Here, we review perivascular space anatomy, physiology and pathology, particularly as seen with MRI in humans, and consider translation from models to humans to highlight knowns, unknowns, controversies and clinical relevance.