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The mechanosensory hair cell of the vertebrate inner ear responds to the mechanical deflections that result from hearing or change in the acceleration due to gravity, to allow us to perceive and interpret sounds, maintain balance and spatial orientation. In mammals, ototoxic compounds, disease, and acoustic trauma can result in damage and extrusion of hair cells, without replacement, resulting in hearing loss. In contrast, non-mammalian vertebrates can regenerate sensory hair cells. Upon damage, hair cells are extruded and an associated cell type, the supporting cell is transformed into a hair cell. The mechanisms that can trigger regeneration are not known. Using mosaic deletion of the hair cell master gene, Atoh1, in the embryonic avian inner ear, we find that despite hair cells depletion at E9, by E12, hair cell number is restored in sensory epithelium. Our study suggests a homeostatic mechanism can restores hair cell number in the basilar papilla, that is activated when juxtracrine signalling is disrupted. Restoration of hair cell numbers during development may mirror regenerative processes, and our work provides insights into the mechanisms that trigger regeneration.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos , Células Ciliadas Auditivas , Homeostase , Animais , Células Ciliadas Auditivas/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Embrião de Galinha , Epitélio/metabolismo , Deleção de Genes , Regeneração/fisiologia , Contagem de Células , Mosaicismo , Galinhas , Órgão Espiral/embriologia , Órgão Espiral/metabolismoRESUMO
The emergence of new variants of SARS-CoV-2 necessitates unremitting efforts to discover novel therapeutic monoclonal antibodies (mAbs). Here, we report an extremely potent mAb named P4A2 that can neutralize all the circulating variants of concern (VOCs) with high efficiency, including the highly transmissible Omicron. The crystal structure of the P4A2 Fab:RBD complex revealed that the residues of the RBD that interact with P4A2 are a part of the ACE2-receptor-binding motif and are not mutated in any of the VOCs. The pan coronavirus pseudotyped neutralization assay confirmed that the P4A2 mAb is specific for SARS-CoV-2 and its VOCs. Passive administration of P4A2 to K18-hACE2 transgenic mice conferred protection, both prophylactically and therapeutically, against challenge with VOCs. Overall, our data shows that, the P4A2 mAb has immense therapeutic potential to neutralize the current circulating VOCs. Due to the overlap between the P4A2 epitope and ACE2 binding site on spike-RBD, P4A2 may also be highly effective against a number of future variants.
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Enzima de Conversão de Angiotensina 2 , Anticorpos Neutralizantes , COVID-19 , SARS-CoV-2 , Animais , Humanos , Camundongos , Enzima de Conversão de Angiotensina 2/química , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , COVID-19/imunologia , COVID-19/terapia , Camundongos Transgênicos , Testes de Neutralização , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
Introduction Through its National Family Planning Programme, India has been relentlessly working to decrease society's unmet contraception needs. The postpartum period is of paramount importance for addressing these contraceptive needs owing to alterations in fertility and coital behavior associated with childbirth. Depot medroxyprogesterone acetate (DMPA), a long-acting reversible contraceptive, is one of the safe options available in the early postpartum period. In this study, we aimed to evaluate its efficacy and acceptability among postpartum women delivering in Guru Gobind Singh Medical College and Hospital. Methodology We recruited 206 early postpartum women for the study. After thorough counseling and ensuring establishment of lactation, we administered DMPA 150mg by injection intramuscularly and repeated it at intervals of three months in willing patients. We then evaluated them for their symptoms, side effects, and lactation status using a predesigned proforma either during their follow-up visits or telephonically. Results We found DMPA to be 100% efficacious as an early postpartum contraceptive measure. The main reasons for acceptance were its ease of use, long-term effects of a single dose, and noninterference with lactation. However, the continuation rate for the second dose was only 18% in our study, highlighting the need for better counseling and improving awareness among our patients. Ninety-nine percent of our patients were satisfied with their lactation. Conclusion We found injectable DMPA used as a contraceptive in the immediate postpartum period to be a safe and effective alternate method with no deleterious effect on lactation and an acceptable side effect profile. However, more awareness programs are necessary to encourage women, especially those in low-resource areas, to continue using DMPA.
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Spotting fake news is a critical problem nowadays. Social media are responsible for propagating fake news. Fake news propagated over digital platforms generates confusion as well as induce biased perspectives in people. Detection of misinformation over the digital platform is essential to mitigate its adverse impact. Many approaches have been implemented in recent years. Despite the productive work, fake news identification poses many challenges due to the lack of a comprehensive publicly available benchmark dataset. There is no large-scale dataset that consists of Indian news only. So, this paper presents IFND (Indian fake news dataset) dataset. The dataset consists of both text and images. The majority of the content in the dataset is about events from the year 2013 to the year 2021. Dataset content is scrapped using the Parsehub tool. To increase the size of the fake news in the dataset, an intelligent augmentation algorithm is used. An intelligent augmentation algorithm generates meaningful fake news statements. The latent Dirichlet allocation (LDA) technique is employed for topic modelling to assign the categories to news statements. Various machine learning and deep-learning classifiers are implemented on text and image modality to observe the proposed IFND dataset's performance. A multi-modal approach is also proposed, which considers both textual and visual features for fake news detection. The proposed IFND dataset achieved satisfactory results. This study affirms that the accessibility of such a huge dataset can actuate research in this laborious exploration issue and lead to better prediction models.
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Circumflex aorta is described as a retroesophageal aortic arch, with opposite-sided descending aorta forming a true vascular ring with ligamentum arteriosum. We report two cases of right-sided circumflex aorta with varied clinical presentation. Computed tomography diagnosed this vascular ring anomaly. The patients were managed with the aortic uncrossing procedure as a primary surgical strategy. Preoperative diagnosis and thorough planning were essential for the successful outcome. The patients did not have any residual symptoms of tracheal and esophageal compression on follow up.
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Phage display is a proven and widely used technology for selecting specific antibodies against desired targets. However, an immense amount of effort is required to identify and screen the desired positive clones from large and diverse combinatorial libraries. On the other hand, the selection of positive binding clones from synthetic and semi-synthetic libraries has an inherent bias toward clones with randomly produced amber stop codons, making it more difficult to identify desirable binding antibodies. To overcome the screening of desired clones with amber codons, we present a step-by-step approach for effective phage library screening to isolate useful antibodies. The procedure calls for creating a simple new vector system for soluble production of phage ELISA positive binding clones with one or more amber stop codons in their single-chain antibody fragment (scFv) gene sequences, which is otherwise difficult in standard screening. Graphical abstract.
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We used human semi-synthetic phage antibody gene libraries to select anti-SARS-CoV-2 RBD scFv antibody fragment and subsequent characterization of this novel tetravalent monoclonal antibody targeting conformational epitopes in the receptor binding domain of SARS-CoV-2. Binding studies suggest that II62 tetravalent antibody cross-reacts with RBD protein of SARS-CoV2 and its different variants of concerns. The epitope mapping data reveals that II62 tetravalent antibody targets an epitope that does not directly interferes with RBD: ACE2 interaction. Neutralization studies with live authentic SARS-CoV2 virus suggests that increase in valency of II62 mAb from monovalent to tetravalent doesn't perturbate virus interactions with the ACE2 expressing host cells in cytopathic effect-based (CPE) assay. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03272-6.
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Pineoblastoma is an extremely rare intracranial neoplasm, with increased risk of craniospinal metastasis. There is only one case reported in the literature who presented during pregnancy. Described here is a woman who presented at five months of gestation with recurrence of pineoblastoma, who had previously defaulted adjuvant therapy following surgical decompression. The challenges in the diagnosis and treatment of pineoblastoma and its effects on pregnancy are also discussed.
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Sentiment analysis research has been increasing tremendously in recent times due to the wide range of business and social applications. Sentiment analysis from unstructured natural language text has recently received considerable attention from the research community. In this paper, we propose a novel sentiment analysis model based on common-sense knowledge extracted from ConceptNet based ontology and context information. ConceptNet based ontology is used to determine the domain specific concepts which in turn produced the domain specific important features. Further, the polarities of the extracted concepts are determined using the contextual polarity lexicon which we developed by considering the context information of a word. Finally, semantic orientations of domain specific features of the review document are aggregated based on the importance of a feature with respect to the domain. The importance of the feature is determined by the depth of the feature in the ontology. Experimental results show the effectiveness of the proposed methods.
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Algoritmos , Inteligência Artificial , Semântica , Sensação/fisiologiaRESUMO
Background: Bariatric surgery is seen as one of the most successful option for the control of morbid obesity and obesity related complications. Although, there are many surgical options available the Lincey Alexida, Xiaohua Qi, Patrick B. Asdell, José M. Martínez Landrón, Samarth B. Patel, Faustino Allongo. Frederick Tiesenga. Laparoscopic Adjustable Gastric Band as a Revision Surgery for Failed Vertical Gastric Sleeve or Roux-en-Y Gastric Bypass. IAIM, 2017; 4(12): 37-42. Page 38 laparoscopic vertical sleeve gastrectomy and the Roux-en-Y gastric bypass are among the most selected treatment methods. Even though the sleeve gastrectomy and the gastric bypass has proven to be efficacious in weight reduction in morbid obesity there are still some reported failures. Aim: This study main objective is to see if an adjustable gastric band can be offered as a sensible option for patients who have had a previously failed vertical sleeve gastrectomy or the Roux-en-Y gastric bypass surgery. The procedure will be classified as a revision surgery to increase the possibilities of additional weight loss not achieved with the sleeve gastrectomy or gastric bypass surgery alone. Method: A retrospective review of the charts for all the bariatric patients from April 2012 to April 2017 was conducted. The chart review yielded 12 patients who underwent either adjustable band over a previously failed vertical sleeve procedure or the adjustable band over a previously failed Roux-enY gastric bypass procedure. The patients were divided into two groups, group A and B. Group A is comprised of the 8 out 12 patients who had a previous failed gastric sleeve procedure. Group B has the remaining 4 patients who had a failed gastric bypass procedure. Observation: Both groups who underwent adjustable gastric band laparoscopically as a revision procedure after a two year follow up appointment showed Group A had a mean estimate weight loss of 30.75 lbs. (11%) with a mean Body Mass Index of 40.7 kg/m2 and Group B had a mean estimate weight loss of 42 lbs. (15%) with a mean Body Mass Index of 36.77 kg/m2 . Group A had an Excess Body Weight Loss of 27% at 1 month and 33% at the 2 year follow up and Group B had an Excess Body Weight Loss of 42.2%. Group B had an Excess Body Weight Loss of 15.1 % at 1 month and 42.2% at the 2 year follow up. Conclusion: Group A had an average of 27% Excess Body Weight Loss and Group B had an Excess Body Weight Loss of 15.1% after 1 month on follow up. Our study was limited by the small sample size. We suggest that further investigational studies, with greater and more diverse sample sizes, be conducted to assure the benefit of using the adjustable gastric band as a revision surgery. Based on our results we conclude that the adjustable gastric band as a revision surgery is a promising and sensible alternative treatment option for patients with a previously failed laparoscopic vertical sleeve gastrectomy or a failed Roux-en-Y gastric bypass.
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Background: Hip fractures in older patients are associated with impaired mobility, excess morbidity and mortality, and loss of independence. Objectives: To determine whether total hip arthroplasty is associated with lower reoperation rates, mortality, and complications, and better function and quality of life than hemiarthroplasty for displaced fractures of the femoral neck in older patients. Materials and methods: We prospectively as well as retrospectively studied 46 patients treated with total hip replacement or hemiarthroplasty. Pain, range of motion, hip function, haris hip score and complications were assessed clinically while hip stability, femoral anteversion, acetabular cup inclination and acetabular erosions were assessed radiographically. Results: In our study according to Harris hip score, group A (hemiarthroplasty group) showed 58.33% excellent to good result whereas 33.34% shows fair to poor result. In group B (total hip replacement group) 90.91% showed excellent to good result and 9.08% showed fair to poor result. In this study, the overall Harris hip score was 76.33 with SD±19.091 in hemiarthroplasty group and 86.45 with SD±6.363 in Total hip replacement group with p-value 0.0224(<0.05). Nitin Kumar Singh, Himanshu Jain, Sonal Garg, Sachin Yadav. Primary total hip arthroplasty versus hemiarthroplasty for displaced neck femur fractures in older patients. IAIM, 2017; 4(10): 209-215. Page 210 Conclusion: So we concluded in our one year of study that total hip replacement had better functional outcome in fracture neck of femur in elderly treated by either hemiarthroplasty or total hip replacement and total hip replacement is less painful than hemiarthroplasty.
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xMajority of osteoporotic vertebral compression fracture present with back pain and some of them with spinal deformity. Percutaneous vertebroplasty not only addresses pain relief but also the correction of spinal deformity with least post-operative morbidity. 72 patients with osteoporotic compression fracture and spinal deformity with chronic invalidating pain treated with percutaneous vertebroplasty were followed for 2.8 years with an average of 1.3 years.47% showed excellent,13% showed good and 40% showed fair result on vas score. There was good improvement in stature in 43%, fair in 40% and 17% showed no improvement.
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T-cell lymphoma (TCL) is a biologically diverse and uncommon group of lymphoid malignant diseases. Compared with its B-cell counterparts, TCL is notably more difficult to diagnose and manage owing to its rarity and biologic heterogeneity. Hepatosplenic TCL is an extremely rare subtype of TCL. A 37-year-old Indian male presented to his physician with swelling and pain in left hypochondrium. Clinical examination revealed pallor, icterus and massive splenomegaly. His blood examination revealed pancytopenia. His bone marrow biopsy was suggestive of lymphoma. Whole body F-18 flourodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan revealed diffuse increased metabolic activity in massively enlarged spleen, liver and bone marrow. There was no evidence of metabolically active lymphadenopathy anywhere in the body. Guided by the FDG PET/CT findings, a liver biopsy was advised. Liver histopathology revealed the presence of hepatosplenic TCL. A final diagnosis of hepatosplenic TCL with liver, spleen and bone marrow involvement was made. Even though rare, hepatosplenic TCL should be considered as a possible diagnosis in patients presenting with similar clinical picture and FDG PET/CT scan findings.