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1.
Front Mol Neurosci ; 15: 822863, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548668

RESUMO

TDP-43 proteinopathies is a disease hallmark that characterizes amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The N-terminal domain of TDP-43 (NTD) is important to both TDP-43 physiology and TDP-43 proteinopathy. However, its folding and dimerization process is still poorly characterized. In the present study, we have investigated the folding/unfolding of NTD employing all-atom molecular dynamics (MD) simulations in 8 M dimethylsulfoxide (DMSO) at high temperatures. The MD results showed that the unfolding of the NTD at high temperature evolves through the formation of a number of conformational states differing in their stability and free energy. The presence of structurally heterogeneous population of intermediate ensembles was further characterized by the different extents of solvent exposure of Trp80 during unfolding. We suggest that these non-natives unfolded intermediate ensembles may facilitate NTD oligomerization and subsequently TDP-43 oligomerization, which might lead to the formation of irreversible pathological aggregates, characteristics of disease pathogenesis.

2.
Arch Microbiol ; 204(6): 341, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35593972

RESUMO

Endophytes are microbes that live inside the tissues of plants without causing any disease. Many of these belonging to fungi have been exploited earlier for their biological activities. This study focused on the exploration and characterization of culturable endophytic fungi inhabiting the medicinal plant Dillenia indica L. during four different seasons (summer, monsoon, autumn, and winter) from 2018 to 2019. A total of 2360 segments from different parts (leaves, fruits, and stem) were screened to isolate endophytic fungi. During the study, 25 species of fungi belonging to 20 genera were isolated from the selected plant. The identification of these fungi was validated at morphological, microscopic, and molecular levels. Results indicate the plant has the highest affinity for Daldinia eschscholtzii, followed by Colletotrichum gloeosporioides and Cladosporium cladosporioides. Further, the percent frequency was highest in leaves, followed by stem and fruits. The results were further supported by a similar trend of colonization rate for different plant parts. The monsoon season had the highest number of isolates (312), followed by summer (208), winter (164), and autumn (114). Species diversity was highest during the monsoon season and lowest during the winter. These fungi also produce amylase, lipase, protease, asparaginase, cellulase, and ligninolytic enzymes. This study focused only on culturable fungal endophytes, yet the scope can be extended for other non-culturable microbes and their interaction by using high-throughput genomics and novel next-generation sequencing (NGS) tools. The results indicate that Dillenia indica L. harbors novel endophytic fungi having industrial applications.


Assuntos
Dilleniaceae , Plantas Medicinais , Endófitos , Fungos , Folhas de Planta/microbiologia , Plantas Medicinais/microbiologia , Estações do Ano
3.
S Afr J Bot ; 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35530267

RESUMO

The widespread COVID-19 pandemic, caused by novel coronavirus SARS-CoV-2, has emanated as one of the most life-threatening transmissible diseases. Currently, the repurposed drugs such as remdesivir, azithromycine, chloroquine, and hydroxychloroquine are being employed in the management of COVID-19 but their adverse effects are a matter of concern. In this regard, alternative treatment options i.e., traditional medicine, medicinal plants, and their phytochemicals, which exhibit significant therapeutic efficacy and show a low toxicity profile, are being explored. The current review aims at unraveling the promising medicinal plants, phytochemicals, and traditional medicines against SARS-CoV-2 to discover phytomedicines for the management of COVID-19 on the basis of their potent antiviral activities against coronaviruses, as demonstrated in various biochemical and computational chemical biology studies. The review consists of integrative and updated information on the potential traditional medicines against COVID-19 and will facilitate researchers to develop traditional medicines for the management of COVID-19.

4.
JMIR Form Res ; 6(5): e34852, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35551059

RESUMO

BACKGROUND: As mobile phone uptake in India continues to grow, there is also continued interest in mobile platform-based interventions for health education. There is a significant gender gap in mobile phone access-women's access to mobile phones is constrained by economic and social barriers. Pregnancy and postpartum care is one of many targets for mobile health (mHealth) interventions that particularly rely upon women's access to and facility with mobile phone use. OBJECTIVE: We aimed to describe the dynamics and patterns of married pregnant and postpartum women's mobile phone access and use (among both phone owners and nonowners) who participated in an mHealth postpartum care intervention and to identify potential barriers to their participation in mobile platform-based interventions. METHODS: A secondary analysis was performed on mixed methods data obtained for a pilot mHealth intervention for postpartum care of mothers in rural Punjab from July 2020 to February 2021. Two formative sources included exploratory in-depth interviews among postpartum women (n=20; 1-3 months postpartum) and quantitative maternal health survey among women who were pregnant or who had recently given birth (n=102). We also utilized mixed methods intervention assessment data from early postpartum women who participated in the pilot intervention (n=29), including intervention moderator perspectives. Qualitative and quantitative analyses were performed, and pertinent findings were grouped thematically. RESULTS: The majority of women owned a phone (maternal health survey: 75/102, 74%; demographic survey: 17/29, 59%), though approximately half (53/102, 52%) still reported sharing phones with other family members. Sharing a phone with female family members typically allowed for better access than sharing with male family members. Some households had strict preferences against daughters-in-law having phones, or otherwise significantly restricted women's phone access. Others reported concerns about phone use-related health hazards for mother and infant during the pregnancy or postpartum period. CONCLUSIONS: These findings suggest nuance regarding what is meant by women's phone ownership and access-there were numerous additional constraints on women's use of phones, particularly during pregnancy and the postpartum period. Future research and mHealth interventions should probe these domains to better understand the dynamics governing women's access, use, and fluency with mobile phones to optimally design mHealth interventions.

5.
Artigo em Inglês | MEDLINE | ID: mdl-35564539

RESUMO

Natural and anthropogenic electromagnetic fields (EMFs) are ubiquitous in the environment and interfere with all biological organisms including plants. Particularly the quality and quantity of alternating EMFs from anthropogenic sources are increasing due to the implementation of novel technologies. There is a significant interest in exploring the impact of EMFs (similar to those emitted from battery chargers of electric cars) on plants. The model plant Arabidopsis thaliana was exposed to a composite alternating EMF program for 48 h and scrutinized for molecular alterations using photosynthetic performance, metabolite profiling, and RNA sequencing followed by qRT-PCR validation. Clear differences in the photosynthetic parameters between the treated and control plants indicated either lower nonphotochemical quenching or higher reduction of the plastoquinone pool or both. Transcriptome analysis by RNA sequencing revealed alterations in transcript amounts upon EMF exposure; however, the gene ontology groups of, e.g., chloroplast stroma, thylakoids, and envelope were underrepresented. Quantitative real-time PCR validated deregulation of some selected transcripts. More profound were the readjustments in metabolite pool sizes with variations in photosynthetic and central energy metabolism. These findings together with the invariable phenotype indicate efficient adjustment of the physiological state of the EMF-treated plants, suggesting testing for more challenging growth conditions in future experiments.

6.
Epidemics ; 39: 100562, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35561500

RESUMO

Visceral leishmaniasis (VL) is declining in India and the World Health Organization's (WHO) 2020 'elimination as a public health problem' target has nearly been achieved. Intensified combined interventions might help reach elimination, but their impact has not been assessed. WHO's Neglected Tropical Diseases 2021-2030 roadmap provides an opportunity to revisit VL control strategies. We estimated the combined effect of a district-wide pilot of intensified interventions in the highly-endemic Vaishali district, where cases fell from 3,598 in 2012-2014 to 762 in 2015-2017. The intensified control approach comprised indoor residual spraying with improved supervision; VL-specific training for accredited social health activists to reduce onset-to-diagnosis time; and increased Information Education & Communication activities in the community. We compared the rate of incidence decrease in Vaishali to other districts in Bihar state via an interrupted time series analysis with a spatiotemporal model informed by previous VL epidemiological estimates. Changes in Vaishali's rank among Bihar's endemic districts in terms of monthly incidence showed a change pre-pilot (3rd highest out of 33 reporting districts) vs. during the pilot (9th) (p<1e-10). The rate of decline in Vaishali's incidence saw no change in rank at 11th highest, both pre-pilot & during the pilot. Counterfactual model simulations suggest an estimated median of 352 cases (IQR 234-477) were averted by the Vaishali pilot between January 2015 and December 2017, which was robust to modest changes in the onset-to-diagnosis distribution. Strengthening control strategies may have precipitated a substantial change in VL incidence in Vaishali and suggests this approach should be piloted in other highly-endemic districts.

7.
Indian J Crit Care Med ; 26(3): 401-402, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35519923

RESUMO

Platypnea-orthdeoxia syndrome (POS) is a clinical scenario where patient get breathless while sitting or standing. Its important causes are cardiac shunts, hepatopulmonary syndrome and pulmonary ventilation perfusion mismatch. During this pandemic as cases of pulmonary fibrosis increased, we find POS as one of the important cause of morbidity during recovery. Early recognition of this will decrease the morbidity and unrealistic expectation of fast recovery. How to cite this article: Bhushan D, Kumar V, Sahoo BH, Hegde A. Platypnea-orthodeoxia Syndrome: An Important Cause of Morbidity in Post Coronavirus Disease Patients. Indian J Crit Care Med 2022;26(3):401-402.

8.
Oral Oncol ; 129: 105869, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35483157

RESUMO

BACKGROUND: Topical fluoride is used for prevention of dental caries. However, its effectiveness and more specifically its formulation and frequency of application in patients undergoing head and neck radiotherapy are still debatable. The aim of this systematic review was to pool the evidence of effectiveness of various topical fluorides in preventing radiation caries or change in bacterial growth in adult patients of head and neck cancer. METHODS: Three databases (PubMed and Google Scholar and Cochrane) were searched for randomized controlled or uncontrolled trials or quasi randomised trials published till February 2021. Two independent reviewers screened 346 abstracts finally 14 articles were included in the current systematic review. Primary outcome evaluated was the prevention of radiation caries or change in bacterial growth in saliva. Meta-analysis was performed for the sub groups formed on the basis of fluoride formulations and adjuncts used with it. RESULTS: Studies included were highly heterogeneous. Majority of studies found different fluoride formulations to be effective in controlling radiation caries to a variable extent up to 70% depending upon the intervention, patient compliance, rate of attrition and follow up period. Sodium fluoride was the most commonly used caries preventive agent. Meta-analysis showed no significant difference between sodium fluoride formulations and other fluoride agents. Fluoride treatment when incorporated with re-mineralising agent had no significant effect on caries prevention CONCLUSION: Fluoride prevents radiation caries. However, to delineate its exact formulation, dosage or frequency, there is need for more well conducted randomised controlled trials.

9.
RSC Adv ; 12(8): 4780-4794, 2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35425477

RESUMO

The current study uses the free radical graft copolymerization of acrylic acid as a monomer, N,N-methylene-bis-(acrylamide) as a crosslinker and ammonium persulfate as an initiator to synthesise GG-cl-poly(AA) hydrogels based on gellan gum utilising response surface methodology (RSM). A full factorial design was used to obtain the greatest percent swelling (P s), and key process variables were determined using the Pareto chart. To make the procedure cost-effective, a multiple regression model employing ANOVA projected a linear model with a maximum percentage swelling of 556 at the lowest concentration of all three studied factors. As a result, the sequential experimental design was successful in obtaining two-fold increases in the percentage swelling in a systematic way. An RSM-based central composite design was used to optimize the percentage swelling of the three most important synthesis parameters: initiator concentration, monomer concentration, and crosslinker concentration. The best process conditions are 7.3 mM L-1 initiator, 44 µM L-1 monomer, and 21.6 mM L-1 crosslinker. The effective synthesis of GG-cl-poly(AA) was validated by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, field emission scanning electron microscopy (FE-SEM), and 1H-nuclear magnetic resonance. The swelling behavior of GG-cl-poly(AA) in water and saline solutions, as well as its water retention capability, was investigated. In comparison to distilled water, the swelling potential of optimized hydrogel was shown to be significantly reduced in saline solutions. The addition of GG-cl-poly(AA) significantly improved the moisture properties of plant growth media (clay, sandy, and clay-soil combination), implying that it has great potential in moisture stress agriculture. GG-cl-poly(AA) biodegradation was studied by soil burial and vermicomposting methods. The composting approach showed 89.95% deterioration after 22 days, while the soil burial method showed 86.71% degradation after 22 days. The synthesized hydrogel may be beneficial for agricultural applications because of its considerable degradation behaviour, strong water retention capacity, low cost, and environmental friendliness.

10.
Multimed Tools Appl ; : 1-18, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35431606

RESUMO

The latest threat to global health is the coronavirus disease 2019 (COVID-19) pandemic. To prevent COVID-19, recognizing and isolating the infected patients is an essential step. The primary diagnosis method is Reverse Transcription Polymerase Chain Reaction (RT-PCR) test. However, the sensitivity of this test is not satisfactory to successfully control the COVID-19 outbreak. Although there exist many datasets of chest X-rays (CXR) images, but few COVID-19 CXRs are presently accessible owing to privacy of patients. Thus, many researchers have utilized data augmentation techniques to augment the datasets. But, it may cause over-fitting issues, as the existing data augmentation techniques include small modifications to CXRs. Therefore, in this paper, an efficient deep convolutional generative adversarial network and convolutional neural network (DGCNN) is designed to diagnose COVID-19 suspected subjects. Deep convolutional generative adversarial network (DGAN) consists of two networks trained adversarially such that one generates fake images and the other differentiates between them. Thereafter, convolutional neural network (CNN) is utilized for classification purpose. Extensive experiments are conducted to evaluate the performance of the proposed DGCNN. Performance analysis demonstrates that DGCNN can highly improves the diagnosis performance.

11.
Toxicol Mech Methods ; : 1-9, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35403558

RESUMO

Background: Monocrotophos (MCP) is an organophosphate pesticide with well-known toxicity in mammals. Exposure of MCP is associated with altered molecular physiology at sub-cellular levels. This study investigated the efficacy of N-acetylcysteine (NAC) against MCP exposure mediated mitochondrial dysfunctions in hepatic tissue of rats.Methods: Male Wistar rats were given NAC (200 mg/kg b.wt), MCP (0.9 mg/kg b.wt) and NAC together with MCP, intragastrically for 28 consecutive days. Mitochondrial complexes activities were evaluated using biochemical analysis. mRNA expression of mitochondrial complexes subunits, PGC-1α and its downstream regulators were analyzed using polymerase chain reaction.Results: Exposure of MCP (0.9 mg/kg b.wt, intragastrically, 28 d) decreased mitochondrial complexes activities and gene expression of complexes subunits. The expression of PGC-1α, NRF-1, NRF-2, and Tfam was also reduced significantly. The administration of NAC (200 mg/kg b.wt, intragastrically, 28 d) significantly increased mitochondrial complexes activities and gene expression of complexes subunits. Additionally, NAC also maintained mitochondrial functions, and enhanced the gene expression of PGC-1α and its downstream regulators.Conclusion: The results of this study indicate that NAC prevents hepatic mitochondrial dysfunctions and maintains PGC-1α signaling. In conclusion, NAC might be speculated as a therapeutic agent for mitochondrial dysfunctions following toxic exposures.

12.
Biomed Pharmacother ; 150: 113032, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35486977

RESUMO

In MYCN-amplified neuroblastoma (NB), we noticed that the single compound treatment with the HDAC inhibitor vorinostat led to a reprogramming of the glycolytic pathway in these cells. This reprogramming was upregulation of fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS), allowing the cells to generate ATP, albeit at a reduced rate. This behavior was dependent on reduced levels of MYCN and a corresponding increase in the levels of PPARD transcription factors. By integrating metabolic and functional studies in NB cells and mouse xenografts, we demonstrate a compensatory upregulation of FAO/OXPHOS metabolism that promotes resistance to HDAC inhibitors. From the additional compounds that could reverse this metabolic reprogramming, the mTORC1 inhibitor sirolimus was selected. Besides both a block of glycolysis and OXPHOS, the HDAC/mTORC1 inhibitor combination produced significantly higher levels of reactive oxygen species (ROS) in the treated cells and in xenograft tumor samples, also a consequence of increased glycolytic block. The lead compounds were also tested for changes in the message levels of the glycolytic enzymes and their pathway activity, and HK2 and GPI glycolytic enzymes were most affected at their RNA message level. This combination was seen with no overall toxicity in treated mice in terms of weight loss or liver/kidney function.

13.
J Endod ; 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35405158

RESUMO

The management of traumatic dental injury aims at functional and esthetic rehabilitation. After luxation injury, a displaced tooth must be replaced into its normal position as soon as possible. Incorrect tooth repositioning can cause discomfort to the patient and compromise the outcome. This report documents a novel digital technology-based approach for the management of teeth following luxation injury with displacement. A 25-year-old female reported 2 days after traumatic dental injury to her maxillary right central incisor tooth #8. After clinical and radiographic examination, a diagnosis of lateral luxation of tooth #8 was made. The preoperative high-resolution cone-beam computed tomography (CBCT) image data set confirmed palatal luxation of tooth #8 with fractured and displaced labial cortical plate. The CBCT data were imported into a medical image processing software program, and a segmentation tool was used to segment the fractured cortical plate, luxated tooth, and alveolar process. The socket is reconstructed by realigning fractured cortical bone over the alveolar process and repositioning the tooth in the virtual planning software. A three-dimensional (3D) guiding template was designed over the repositioned tooth and adjacent teeth and printed. This 3D printed guide was used for the repositioning of luxated tooth #8 and stabilizing it during the splinting procedure. This technique of using CBCT and 3D guide for repositioning is an objective, precise, and predictable approach. The 3D printed model of the dental arch after virtual tooth alignment can be used by the dentist to determine the exact splint length and contour before splinting.

14.
J Healthc Eng ; 2022: 6216273, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35422979

RESUMO

In this paper, modifications in neoteric architectures such as VGG16, VGG19, ResNet50, and InceptionV3 are proposed for the classification of COVID-19 using chest X-rays. The proposed architectures termed "COV-DLS" consist of two phases: heading model construction and classification. The heading model construction phase utilizes four modified deep learning architectures, namely Modified-VGG16, Modified-VGG19, Modified-ResNet50, and Modified-InceptionV3. An attempt is made to modify these neoteric architectures by incorporating the average pooling and dense layers. The dropout layer is also added to prevent the overfitting problem. Two dense layers with different activation functions are also added. Thereafter, the output of these modified models is applied during the classification phase, when COV-DLS are applied on a COVID-19 chest X-ray image data set. Classification accuracy of 98.61% is achieved by Modified-VGG16, 97.22% by Modified-VGG19, 95.13% by Modified-ResNet50, and 99.31% by Modified-InceptionV3. COV-DLS outperforms existing deep learning models in terms of accuracy and F1-score.


Assuntos
COVID-19 , Aprendizado Profundo , COVID-19/diagnóstico por imagem , Humanos , Radiografia , SARS-CoV-2 , Raios X
15.
Asian J Psychiatr ; 73: 103127, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35430497

RESUMO

Auditory Signal Detection (ASD) theory postulates that auditory verbal hallucinations (AVH) result from an aberrant association of meaningful connection to abstract noises. In this study, schizophrenia (SZ) patients with persistent AVH (N = 17) and matched controls (N = 25) performed an ASD task with concurrent functional near-infrared spectroscopy recording targetting the left dorsolateral prefrontal cortex (L-DLPFC) and left temporoparietal junction (L-TPJ). During the task, discriminability index had a significant negative correlation, and early deoxyhemoglobin (HbR) latency at L-TPJ positively correlated with AVH scores. Also, patients had significantly lower discriminability, early HbR latency at L-TPJ, and delayed latency at L-DLPFC. This finding suggests the presence of ASD abnormalities and impaired auditory processing in SZ patients with AVH supporting ASD-based pathogenesis.

16.
J Med Virol ; 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35467029

RESUMO

Peripheral blood smear (PBS) changes in coronavirus disease 2019 (COVID-19) are diverse and have been reported in the literature in the form of case series with relatively smaller sample sizes and with a handful of studies showing the association between PBS and clinical severity. This study aims to highlight the numerical and morphological changes in peripheral blood of COVID-19 patients and to compare the same in intensive care unit (ICU) and non-ICU settings as well as with disease severity and outcome. The study included 80 COVID-19 positive (41 ICU and 39 non-ICU) patients and 32 COVID-19 negative ICU patients. Complete blood counts (CBCs) and PBS findings were studied and scored by two pathologists blindfolded. Absolute lymphocyte count (ALC) and absolute eosinophil count (AEC) were significantly lower in COVID-19 positive cases as compared to the COVID-19 negative group (p = 0.001 and p = 0.001). COVID-19 positive group showed significant left myeloid shift (p = 0.021), Dohle bodies (p = 0.025) with significant prominence of acquired pseudo-Pelger-Huët anomaly, ring-shaped neutrophils, monolobate neutrophils, and plasmacytoid lymphocytes as compared to control group (p = 0.000, p = 0.009, p = 0.046, and p = 0.011, respectively). The overall mean white blood cell (WBC) counts were higher in COVID-19 positive ICU patients as compared to non-ICU COVID patients with significant shift to left, presence of ring-shaped neutrophils, monocyte vacuolation, and large granular lymphocytes (p = 0.017, p = 0.007, p = 0.008, and p = 0.004, respectively). Deceased group showed significantly higher WBC count (p = 0.018) with marked neutrophilia (p = 0.024) and toxic granulation (p = 0.01) with prominence of monocyte vacuolization, ring-shaped neutrophils, large granular lymphocytes, and reactive lymphocytes. Parameters like myeloid left shift, ring-shaped neutrophils, monocyte vacuolation, and large granular lymphocytes emerged as highly sensitive markers of disease severity. Therefore, serial CBC with comprehensive PBS analysis should be done in every newly diagnosed hospitalized COVID-19 patient which potentially predicts the course of the disease.

17.
Bioorg Med Chem ; 61: 116742, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35398739

RESUMO

Alzheimer's disease (AD) is a multifactorial irreversible neurological disorder which results in cognitive impairment, loss of cholinergic neurons in synapses of the basal forebrain and neuronal death. Exact pathology of the disease is not yet known however, many hypotheses have been proposed for its treatment. The available treatments including monotherapies and combination therapies are not able to combat the disease effectively because of its complex pathological mechanism. A multipotent drug for AD has the potential to bind or inhibit multiple targets responsible for the progression of the disease like aggregated Aß, hyperphosphorylated tau proteins, cholinergic and adrenergic receptors, MAO enzymes, overactivated N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor etc. The traditional approach of one disease-one target-one drug has been rationalized to one drug-multi targets for the chronic diseases like AD and cancer. Thus, over the last decade research focus has been shifted towards the development of multi target directed ligands (MTDLs) which can simultaneously inhibit multiple targets and stop or slow the progression of the disease. The MTDLs can be more effective against AD and eliminate any possibility of drug-drug interactions. Many important active pharmacophore units have been fused, merged or incorporated into different scaffolds to synthesize new potent drugs. In the current article, we have described various hypothesis for AD and effectiveness of the MTDLs treatment strategy is discussed in detail. Different chemical scaffolds and their synthetic strategies have been described and important functionalities are identified in the chemical scaffold that have the potential to bind to the multiple targets. The important leads identified in this study with MTDL characteristics have the potential to be developed as drug candidates for the effective treatment of AD.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides , Inibidores da Colinesterase/farmacologia , Humanos , Ligantes , Proteínas tau
18.
Biochim Biophys Acta Gen Subj ; 1866(7): 130151, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35421539

RESUMO

α-Synuclein (α-Syn) aggregation/fibrillation is a leading cause of neuronal death and is one of the major pathogenic factors involved in the progression of Parkinson's' disease (PD). Against this backdrop, discovering new molecules as inhibitors or modulators of α-Syn aggregation/fibrillation is a subject of enormous research. In this study, we have shown modulation, disaggregation, and neuroprotective potential of aloin and emodin against α-Syn aggregation/fibrillation. Thioflavin T (ThT) fluorescence assay showed an increase in lag phase from (51.14 ± 2) h to (68.58 ± 2) h and (74.14 ± 3) h in the presence of aloin and emodin respectively. ANS binding assay represents a modulatory effect of these molecules on hydrophobicity which is crucial for aggregates/fibril formation. NMR spectroscopy and tyrosine quenching studies reveal the binding of aloin/emodin with monomeric α-Syn. TEM and DLS micrographs illustrate the attenuating effect of aloin/emodin against the development of large aggregates/fibrils. Our seeding experiments suggest aloin/emodin generate seeding incompetent oligomers that direct the off-pathway aggregation/fibrillation. Also, aloin/emodin capably reduces the fibrils-induced cytotoxicity and disassembles the preexisting amyloid fibrils. These findings provide deep insight into the modulatory mechanism of α-Syn aggregation/fibrillation in the presence of aloin and emodin, thereby suggesting their potential roles as promising therapeutic molecules against aggregation/fibrillation related disorders.


Assuntos
Emodina , Doença de Parkinson , Amiloide/metabolismo , Emodina/análogos & derivados , Emodina/farmacologia , Humanos , Doença de Parkinson/tratamento farmacológico , alfa-Sinucleína/química
19.
J Opt Soc Am A Opt Image Sci Vis ; 39(4): 759-765, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35471402

RESUMO

We present a speckle-based deep learning approach for orbital angular momentum (OAM) mode classification. In this method, we have simulated the speckle fields of the Laguerre-Gauss (LG), Hermite-Gauss (HG), and superposition modes by multiplying these modes with a random phase function and then taking the Fourier transform. The intensity images of these speckle fields are fed to a convolutional neural network (CNN) for training a classification model that classifies modes with an accuracy >99%. We have trained and tested our method against the influence of atmospheric turbulence by training the models with perturbed LG, HG, and superposition modes and found that models are still able to classify modes with an accuracy >98%. We have also trained and tested our model with experimental speckle images of LG modes generated by three different ground glasses. We have achieved a maximum accuracy of 96% for the most robust case, where the model is trained with all simulated and experimental data. The novelty of the technique is that one can do the mode classification just by using a small portion of the speckle fields because speckle grains contain the information about the original mode, thus eliminating the need for capturing the whole modal field, which is modal dependent.

20.
J Educ Health Promot ; 11: 58, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372609

RESUMO

BACKGROUND: The world is worsely hit by the COVID-19 pandemic resulting in increased morbidity and mortality. Increased mortality has been observed in older adults with multiple comorbidities. Six-minute walk distance (6MWD) at admission can help us to guide the requirement of oxygen during hospital stay that can be used to determine which patient can be managed at home. MATERIALS AND METHODS: This study was a prospective observational study conducted on COVID-19 patients admitted at AIIMS, New Delhi, from October to December 2020. Patients aged more than 60 years were included in the study and underwent 6-min walk tests. Polypharmacy and multimorbidity were also assessed along with dyspnea which was measured on BORG scale. P < 0.05 was considered statistically significant. Statistical software STATA (version 14.2) was used for all the analyses. RESULTS: The mean age of the study population was 68.76 (7.4). Oxygen saturation prior to the 6-MWT was normal and has significantly higher than the post test (P ≤ 0.001). 6MWD was significantly correlated with pre values of oxygen saturation. 6MWD was observed more in patients who did not require oxygen during hospital stay. Self-reported dyspnea, pulse rate, oxygen saturation, and systolic blood pressure were significantly associated with the patients who had an oxygen requirement during the hospital stay. CONCLUSION: Self-reported dyspnea after 6MWT was found to be associated with oxygen requirement during hospital stay. Patients who have covered more distance in 6-min walk test have less oxygen requirement during hospital stay hence can be managed at home. This will reduce the health-care burden and will help to tackle the outburst during the ongoing pandemic.

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