Factors influencing students' satisfaction with continuous use of learning management systems during the COVID-19 pandemic: An empirical study.

COVID-19 has impacted educational processes in most countries: some educational institutions have closed, while others, particularly in higher education, have converted to online learning systems, due to the advantages offered by information technologies. This study analyzes the critical factors influencing students' satisfaction with their continuing use of online learning management systems in higher education during the COVID-19 pandemic. Through the integration of social cognitive theory, expectation confirmation theory, and DeLone and McLean's IS success model, a survey was conducted of 181 UK students who engaged with learning management systems. It was found that, during the pandemic, service quality did not influence students' satisfaction, although both information quality and self-efficacy had significant impacts on satisfaction. In addition, the results revealed that neither self-efficacy nor satisfaction impacted personal outcome expectations, although prior experience and social influence did. The findings have practical implications for education developers, policymakers, and practitioners seeking to develop effective strategies for and improve the use of learning management systems during the pandemic.

Trans-blood brain barrier delivery of dopamine-loaded nanoparticles reverses functional deficits in parkinsonian rats.

Sustained and safe delivery of dopamine across the blood brain barrier (BBB) is a major hurdle for successful therapy in Parkinson's disease (PD), a neurodegenerative disorder. Therefore, in the present study we designed neurotransmitter dopamine-loaded PLGA nanoparticles (DA NPs) to deliver dopamine to the brain. These nanoparticles slowly and constantly released dopamine, showed reduced clearance of dopamine in plasma, reduced quinone adduct formation, and decreased dopamine autoxidation. DA NPs were internalized in dopaminergic SH-SY5Y cells and dopaminergic neurons in the substantia nigra and striatum, regions affected in PD. Treatment with DA NPs did not cause reduction in cell viability and morphological deterioration in SH-SY5Y, as compared to bulk dopamine-treated cells, which showed reduced viability. Herein, we report that these NPs were able to cross the BBB and capillary endothelium in the striatum and substantia nigra in a 6-hydroxydopamine (6-OHDA)-induced rat model of PD. Systemic intravenous administration of DA NPs caused significantly increased levels of dopamine and its metabolites and reduced dopamine-D2 receptor supersensitivity in the striatum of parkinsonian rats. Further, DA NPs significantly recovered neurobehavioral abnormalities in 6-OHDA-induced parkinsonian rats. Dopamine delivered through NPs did not cause additional generation of ROS, dopaminergic neuron degeneration, and ultrastructural changes in the striatum and substantia nigra as compared to 6-OHDA-lesioned rats. Interestingly, dopamine delivery through nanoformulation neither caused alterations in the heart rate and blood pressure nor showed any abrupt pathological change in the brain and other peripheral organs. These results suggest that NPs delivered dopamine into the brain, reduced dopamine autoxidation-mediated toxicity, and ultimately reversed neurochemical and neurobehavioral deficits in parkinsonian rats.

Involvement of dopaminergic and serotonergic systems in the neurobehavioral toxicity of lambda-cyhalothrin in developing rats.

In view of extensive uses of lambda-cyhalothrin, a new generation type II synthetic pyrethroid, human exposure is quite imminent. The present study has therefore been carried out to investigate effect of lambda-cyhalothrin on brain dopaminergic and serotonergic systems and functional alterations associated with them. Post-lactational exposure to lambda-cyhalothrin (1.0 mg/kg or 3.0 mg/kg body weight, p.o.) from PD22 to PD49 caused a significant decrease in the motor activity and rota-rod performance in rats on PD50 as compared to controls. Decrease in motor activity in lambda-cyhalothrin treated rats was found to persist 15 days after withdrawal of exposure on PD65 while a trend of recovery in rota-rod performance was observed. A decrease in the binding of ³H-Spiperone, known to label dopamine-D2 receptors in corpus striatum associated with decreased expression of tyrosine hydroxylase (TH)-immunoreactivity and TH protein was observed in lambda-cyhalothrin treated rats on PD50 and PD65 compared to controls. Increase in the binding of ³H-Ketanserin, known to label serotonin-2A receptors in frontal cortex was observed in lambda-cyhalothrin exposed rats on PD50 and PD65 as compared to respective controls. The changes were more marked in rats exposed to lambda-cyhalothrin at a higher dose (3.0 mg/kg) and persisted even 15 days after withdrawal of exposure. The results exhibit vulnerability of developing rats to lambda-cyhalothrin and suggest that striatal dopaminergic system is a target of lambda-cyhalothrin. Involvement of serotonin-2A receptors in the neurotoxicity of lambda-cyhalothrin is also suggested. The results further indicate that neurobehavioral changes may be more intense in case exposure to lambda-cyhalothrin continues.

Cholinergic dysfunctions and enhanced oxidative stress in the neurobehavioral toxicity of lambda-cyhalothrin in developing rats.

This study is focused on understanding the mechanism of neurobehavioral toxicity of lambda-cyhalothrin, a new generation type II synthetic pyrethroid in developing rats following their exposure from post-lactational day (PLD)22 to PLD49 and investigate whether neurobehavioral alterations are transient or persistent. Post-lactational exposure to lambda-cyhalothrin (1.0 or 3.0 mg/kg body weight, p.o.) affected grip strength and learning activity in rats on PLD50 and the persistent impairment of grip strength and learning was observed at 15 days after withdrawal of exposure on PLD65. A decrease in the binding of muscarinic-cholinergic receptors in frontocortical, hippocampal, and cerebellar membranes associated with decreased expression of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in hippocampus was observed following exposure to lambda-cyhalothrin on PLD50 and PLD65. Exposure to lambda-cyhalothrin was also found to increase the expression of growth-associated protein-43 in hippocampus of rats on PLD50 and PLD65 as compared to controls. A significant increase in lipid peroxidation and protein carbonyl levels and decreased levels of reduced glutathione and activity of superoxide dismutase, catalase, and glutathione peroxidase in brain regions of lambda-cyhalothrin exposed rats were distinctly observed indicating increased oxidative stress. Inhibition of ChAT and AChE activity may cause down-regulation of muscarinic-cholinergic receptors consequently impairing learning activity in developing rats exposed to lambda-cyhalothrin. The data further indicate that long-term exposure to lambda-cyhalothrin at low doses may be detrimental and changes in selected behavioral and neurochemical end points may persist if exposure to lambda-cyhalothrin continues.

Enhanced survival and function of neural stem cells-derived dopaminergic neurons under influence of olfactory ensheathing cells in parkinsonian rats.

Transplantation of neural stem cell (NSC)-derived dopamine (DA) neurons is associated with low survival of cells, which could be due to limited striatal innervations and uneven distribution of graft because of its dense neuronal core, limited host-graft interaction, poor axonal outgrowth, lack of continuous neurotrophic factors supply, and an absence of cell adhesion molecules mediated appropriate developmental cues. Olfactory ensheathing cells (OEC) express a variety of growth factors and cell adhesion molecules and promote axonal regrowth and functional recovery in spinal cord injury in animal models and patients. In the present study, we explored the possibility to increase the survival, function, axonal outgrowth and striatal reinnervation of NSC by co-grafting with OEC in 6-OHDA lesioned parkinsonian rats. In the presence of OEC, significantly enhanced survival of NSC-derived DA neurons and axonal fiber outgrowth was evident in the striatum of NSC+OEC co-grafted rats at 24 weeks post-grafting as compared with NSC alone grafted rats. The increased survival of NSC and their striatal reinnervation was further manifested in the form of significant and substantial restitution of motor function and neurochemical recovery in the co-grafted group. Significant enhanced expression of p75NTR (from OEC) and tyrosine hydroxylase (TH) (from NSC) confirmed the co-localization and survival of both types of cells at the transplantation site in co-grafted rats. Co-grafting results co-related well with our in vitro studies, which suggest that OEC not only significantly increase survival, neurite outgrowth and DA release of NSC-derived DA neuron but also protect against 6-OHDA neurotoxicity in co-culture conditions. These results collectively suggest that OEC increase the survival and function of transplanted NSC in 6-OHDA lesioned parkinsonian rats.

Functional restoration using basic fibroblast growth factor (bFGF) infusion in Kainic acid induced cognitive dysfunction in rat: neurobehavioural and neurochemical studies.

Neurogenesis occurs in dentate gyrus of adult hippocampus under the influence of various mitogenic factors. Growth factors besides instigating the proliferation of neuronal progenitor cells (NPCs) in dentate gyrus, also supports their differentiation to cholinergic neurons. In the present study, an attempt has been made to investigate the neurotrophic effect of bFGF in Kainic acid (KA) induced cognitive dysfunction in rats. Stereotaxic lesioning using (KA) was performed in hippocampal CA3 region of rat's brain. Four-weeks post lesioning rats were assessed for impairment in learning and memory using Y maze followed by bFGF infusion in dentate gyrus region. The recovery was evaluated after bFGF infusion using neurochemical, neurobehavioural and immunohistochemical approaches and compared with lesioned group. Significant impairment in learning and memory (P < 0.01) observed in lesioned animals, four weeks post lesioning exhibited significant restoration (P < 0.001) following bFGF infusion twice at one and four week post lesion. The bFGF infused animals exhibited recovery in hippocampus cholinergic (76%)/ dopaminergic (46%) receptor binding and enhanced Choline acetyltransferase (ChAT) immunoreactivity in CA3 region. The results suggest restorative potential of bFGF in cognitive dysfunctions, possibly due to mitogenic effect on dentate gyrus neurogenic area leading to generation and migration of newer cholinergic neurons.

Theaflavins induced apoptosis of LNCaP cells is mediated through induction of p53, down-regulation of NF-kappa B and mitogen-activated protein kinases pathways.

Prostate cancer (PCA), the most frequently diagnosed malignancy in men, represents an excellent candidate disease for chemoprevention studies because of its particularly long latency period, high rate of mortality and morbidity. Infusion of black tea and its polyphenolic constituents have been shown to possess antineoplastic effects in androgen dependent PCA in both in vivo and in vitro models including transgenic animals. In the present study, we report that black tea polyphenol, Theaflavins (TF)-induced apoptosis in human prostate carcinoma, LNCaP cells is mediated via modulation of two related pathways: up-regulation of p53 and down-regulation of NF-kappa B activity, causing a change in the ratio of pro-and antiapoptotic proteins leading to apoptosis. The altered expression of Bcl-2 family member proteins triggered the release of cytochrome-C and activation of initiator capsase 9 followed by activation of effector caspase 3. Furthermore, TF also affected the protein expression of mitogen activated protein kinases (MAPK) pathways. Our results demonstrated that TF treatment resulted in down-regulation of phospho-extracellular signal-regulated protein kinase (Erk1/2) and phospho-p38 MAPK expressions. We conclude that TF induces apoptosis in LNCaP cells by shifting the balance between pro-and antiapoptotic proteins and down-regulation of cell survival pathways leading to apoptosis. Further extending this work, we also showed that TF induces apoptosis in androgen independent PCA cell line, PC-3 through caspases and MAPKs mediated pathways. Thus, effect of TF on PCA cell lines seems to be irrespective of their androgen status.

Behavioral and neurochemical effects induced by pyrethroid-based mosquito repellent exposure in rat offsprings during prenatal and early postnatal period.

Synthetic pyrethroids, besides their use in agriculture, are prevalently used in our houses as mosquito repellent (MR) in the form of aerosol, mats, coils and liquid vaporizers. Inhalation of fumes of the MR/liquid vaporizers may get entry into the brain by breaching the developing blood-brain barrier, hence deleterious to developing nervous system and can lead to long-term functional deficits. In the present study the consequence of MR exposure has further been investigated at various stages of development, evaluating free radical mediated effect pertinent to neurobehavioral and neurochemical functioning. Rat pups were exposed to pyrethroid-based MR (allethrin 3.6% w/v, 8 h/day through inhalation) during prenatal (GD1-20), postnatal (PND1-30) and perinatal (GD1-PND30) period of development and assessments were made on PND31. We observed significant oxidative stress, where an increase in lipid peroxidation and a decrease in antioxidants, glutathione, superoxide dismutase and catalase in various brain areas (cerebellum, corpus striatum, frontal cortex and hippocampus) were evident at all the exposure schedules. The hippocampus was the most affected region and further exhibited altered cholinergic functioning in the form of significant decrease in cholinergic (muscarinic) receptor binding (prenatal 32%, postnatal 35%, perinatal 38%) and inhibition in acetylcholinesterase activity (prenatal 20%, postnatal 31% and perinatal 33%). The neurochemical changes were found to accompany decrease in learning and memory performance in exposed rats, the function governed by hippocampus. The result suggests that pyrethroid-based MR inhalation during early developmental period may have adverse effect on developing nervous system causing cholinergic dysfunction leading to learning and memory deficit.

Nerve growth factor increases survival of dopaminergic graft, rescue nigral dopaminergic neurons and restores functional deficits in rat model of Parkinson's disease.

In the present study, an attempt has been made to explore the neuroprotective and neurorescue effects of nerve growth factor (NGF) on grafted cells and on host nigral dopaminergic neurons, respectively. NGF was co-transplanted with fetal ventral mesencephalic cells (VMC) in the striatum of 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease (PD). In the other groups fetal VMC and NGF were transplanted alone. Twelve weeks post-transplantation, a significant restoration was observed in D-amphetamine induced rotations (stereotypy), spontaneous locomotor activity, striatal and nigral dopamine (DA) and 3,4-dihydroxy-phenyl acetic acid (DOPAC) levels in co-transplanted rats as compared to VMC alone transplanted rats. Higher number of surviving tyrosine hydroxylase immunoreactive (TH-ir) neurons and significantly increased fiber outgrowth from graft was evident in co-transplanted rats as compared to VMC alone transplanted rats. Further, a significant increase was also observed in substantia nigra TH-ir neurons count in co-transplanted rats, exhibiting a potential neuroprotective and neurorescue effects of NGF on nigrostriatal dopaminergic neurons. The results suggest that NGF at the time of transplantation exhibits neuroprotective effect on transplanted VMC as well as neurorescue effect on remaining host nigral dopaminergic neurons, leading to better functional restoration.

Modulation of P-glycoprotein-mediated multidrug resistance in K562 leukemic cells by indole-3-carbinol.

Resistance to chemotherapeutic drugs is one of the major problems in the treatment of cancer. P-glycoprotein (P-gp) encoded by the mdr gene is a highly conserved protein, acts as a multidrug transporter, and has a major role in multiple drug resistance (MDR). Targeting of P-gp by naturally occurring compounds is an effective strategy to overcome MDR. Indole-3-carbinol (I3C), a glucosinolates present in cruciferous vegetables, is a promising chemopreventive agent as it is reported to possess antimutagenic, antitumorigenic, and antiestrogenic properties in experimental studies. In the present investigation, the potential of I3C to modulate P-gp expression was evaluated in vinblastine (VBL)-resistant K562 human leukemic cells. The resistant K562 cells (K562/R10) were found to be cross-resistant to vincristine (VCR), doxorubicin (DXR), and other antineoplastic agents. I3C at a nontoxic dose (10 x 10(-3) M) enhanced the cytotoxic effects of VBL time dependently in VBL-resistant human leukemia (K562/R10) cells but had no effect on parent-sensitive cells (K562/S). The Western blot analysis of K 562/R 10 cells showed that I3C downregulates the induced levels of P-gp in resistant cells near to normal levels. The quantitation of immunocytochemically stained K562/R10 cells showed 24%, 48%, and 80% decrease in the levels of P-gp by I3C for 24, 48, and 72 h of incubation. The above features thus indicate that I3C could be used as a novel modulator of P-gp-mediated multidrug resistance in vitro and may be effective as a dietary adjuvant in the treatment of MDR cancers.

Reversal of P-glycoprotein-mediated multidrug resistance by diallyl sulfide in K562 leukemic cells and in mouse liver.

Multidrug resistance (MDR) mediated by the overexpression of drug efflux protein P-glycoprotein (P-gp) is one of the major obstacles to successful cancer chemotherapy. P-gp acts as an energy-dependent drug efflux pump, reducing the intracellular concentration of structurally unrelated drugs. Modulators of P-gp function can restore the sensitivity of multidrug-resistant cells to such drugs. In the present study, we evaluated the P-gp modulatory potential of diallyl sulfide (DAS), a volatile organosulfur compound present in garlic, known to possess many medicinal properties, including antimutagenic and anticarcinogenic activities. For in vitro studies, K562 leukemic cells were made resistant (K562/R) to the cytotoxicity of vinblastine (VBL) by progressive adaptation of the sensitive K562 parental cells to VBL. Cross-resistance of K562/R was found between vincristine (VCR), doxorubicin and other antineoplastic agents. A non-toxic concentration of DAS (8.75 x 10(-3) M) enhanced the cytotoxic effects of VBL and another vinca alkaloid, VCR, time dependently in VBL-resistant human leukemia (K562/R10) cells but had no effect on the parent (K562/S) cells. The results show that DAS decreased the induced levels of P-gp in resistant cells back to the normal levels as analyzed both qualitatively and quantitatively by western blotting and immunocytochemistry. Furthermore, in vivo combination studies showed that DAS effectively inhibited vinca alkaloid-induced P-gp overexpression in mouse hepatocytes. Quantitation of immunostained tissue sections with image analysis showed that the reduction in P-gp levels was up to 73% for VBL- and 65% for VCR-induced drug resistance. The above features thus indicate that DAS can serve as a novel, non-toxic modulator of MDR and can be used as a dietary adjuvant.

Comparative effect of dietary administration of Lathyrus sativus pulse on behaviour, neurotransmitter receptors and membrane permeability in rats and guinea pigs.

Neurolathyrism, an upper motor neuron disease, has been thought to be caused by long-term dietary consumption of lathyrus pulse, which contains the toxin beta-N-oxalyl-L-alpha,beta-diaminopropionic acid. Earlier behavioural studies employing oral feeding of lathyrus pulse to animals has been conducted without evaluating the biochemical toxicity potential. In the present investigation the effect of dietary feeding of 10%, 50% and 80% lathyrus pulse to rats and guinea pigs for 3 months on neurobehavioural parameters, including locomotor activity, inclined plain test and neurotoxicological parameters such as neurotransmitter receptor binding, Ca(2+) influx and membrane fluidity, was investigated. Exposure of 50% low and high toxin lathyrus to rats did not cause any significant change in locomotor activity, whereas guinea pigs at the same dosage regimen of high toxin lathyrus showed significant lowering of inclined plain test scores. Furthermore, studies of neuroreceptor binding in rats fed 50% low and high toxin lathyrus showed significant changes in glutamate, dopamine and muscarinic receptors, whereas the benzodiazepine receptor elicited no change. Guinea pigs, on the other hand, fed 50% and 80% lathyrus in the diet showed significant changes in glutamate, dopamine, muscarinic and benzodiazepine receptors. Interestingly, significant elevation in intracellular calcium with a concomitant increase in membrane fluidity was observed in rats (50% low and high toxin) and guinea pigs (50% and 80%) fed a lathyrus diet. These results indicate that although both species (rats and guinea pigs) are susceptible to neurochemical changes on exposure to lathyrus, locomotor changes are only noticed in guinea pigs. Thus, guinea pigs may be more prone to lathyrus toxicity and may serve as a sensitive animal model compared with rats.