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1.
Sci Total Environ ; 951: 175501, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39147067

RESUMO

The present research investigates the dynamics and underlying causes contributing to the exceptional intensity of Super Cyclonic Storm (SuCS) Amphan (16th to 21st May 2020) over the Bay of Bengal (BoB), as well as its impact on aerosol redistribution along the four cities of eastern coast and north-eastern India. Notably, the SuCS was formed during the first phase of the COVID-19 lockdown in India, giving it a unique aspect of study and analysis. Our analysis based on 30 years of climatology data from Modern-Era Retrospective Analysis for Research and Applications, Version 2 (MERRA-2) reanalysis reveals 'positive' monthly anomalous winds (0.8 to 1.6 m/s) prevailed over the central BoB for May 2020. The present study further found the evolution of 'barrier layer thickness'(BLT) leading up to landfall, noting a thickening trend from 8 to 3 days before landfall, contributing to maintaining warmer sea surface temperatures near the coast. Additionally, utilizing European Centre for Medium-Range Weather Forecasts (ECMWF), reanalysis version-5 (ERA-5) data, a mean positive sea surface temperature (SST) anomaly of 0.8 to 1 °C was observed 'before' cyclone period (10-15 May 2020) near the cyclogenesis point. A detailed examination of Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) vertical cross-section plots during the cyclone's intensification stage reveals the presence of high-altitude clouds composed primarily of ice crystals. Further, analysis also indicates that the cyclone transported Sea-salt PM2.5 aerosols from the ocean, dispersing them in the landfall region.The aerosol optical Depth (AOD) data obtained from the National Aeronautics and Space Administration's (NASA) 'Clouds and the Earth's Radiant Energy System (CERES)' mission and MERRA-2 were also analysed, revealing that the cyclone redistributed aerosols over the Bengal basin region (mainly over 'Kolkata') and three other nearby cities along the track of the cyclone (i.e., Bhubaneswar (Odisha) Agartala (Tripura) and Shillong (Meghalaya) respectively).

2.
Nat Struct Mol Biol ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39134711

RESUMO

In mammalian mitochondria, mRNAs are cotranscriptionally stabilized by the protein factor LRPPRC (leucine-rich pentatricopeptide repeat-containing protein). Here, we characterize LRPPRC as an mRNA delivery factor and report its cryo-electron microscopy structure in complex with SLIRP (SRA stem-loop-interacting RNA-binding protein), mRNA and the mitoribosome. The structure shows that LRPPRC associates with the mitoribosomal proteins mS39 and the N terminus of mS31 through recognition of the LRPPRC helical repeats. Together, the proteins form a corridor for handoff of the mRNA. The mRNA is directly bound to SLIRP, which also has a stabilizing function for LRPPRC. To delineate the effect of LRPPRC on individual mitochondrial transcripts, we used RNA sequencing, metabolic labeling and mitoribosome profiling, which showed a transcript-specific influence on mRNA translation efficiency, with cyclooxygenase 1 and 2 translation being the most affected. Our data suggest that LRPPRC-SLIRP acts in recruitment of mitochondrial mRNAs to modulate their translation. Collectively, the data define LRPPRC-SLIRP as a regulator of the mitochondrial gene expression system.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39073131

RESUMO

PURPOSE: To compare time and resource-saving with integration of digital cataract workflow to the existing workflow in high-volume cataract surgery clinics. SETTING: L V Prasad Eye Institute, Hyderabad, India (Site 1) and Narayana Nethralaya, Bengaluru, India (Site 2). DESIGN: Prospective, time-and-motion. METHODS: The total time to complete each step (preoperative measurements, surgical planning, and surgical procedures) of the cataract workflow, number of data fields entered, and support staff required for both workflows were recorded. All study measurements were determined first for existing EMR cataract workflow followed by digital workflow (integrated data management system with data reviewer, surgical planner, and data transfer to OR) at both sites. RESULTS: A total of 85 (Site 1, 44; Site 2, 41) cataract workflows were analyzed. The integration of digital workflow into the site's existing EMR workflow reduced the mean time for preoperative measurements by 25.3% (P = .006), surgical planning by 55.1% (P = .008), and surgical procedures by 22.6% (P = .002). The mean±SD overall time for the surgery was significantly shorter in the digital group (887.3±103.3 vs 1271.3±300.7 seconds; P < .0001). For both sites, the number of data fields recorded and the number of support staff needed was significantly lesser for the digital workflow (P < .0001, for both). CONCLUSIONS: Integration of digital workflow significantly reduced the overall cataract surgery time, variability of overall time, number of data fields recorded, and resource utilization. Complete digitalization has important implications for improving the efficiency and standardization of cataract surgery workflow.

4.
AMIA Jt Summits Transl Sci Proc ; 2024: 266-275, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827059

RESUMO

ChatGPT is a popular information system (over 1 billion visits in August 2023) that can generate natural language responses to user queries. It is important to study the quality and equity of its responses on health-related topics, such as vaccination, as they may influence public health decision-making. We use the Vaccine Hesitancy Scale (VHS) proposed by Shapiro et al.1 to measure the hesitancy of ChatGPT responses in English, Spanish, and French. We find that: (a) ChatGPT responses indicate less hesitancy than those reported for human respondents in past literature; (b) ChatGPT responses vary significantly across languages, with English responses being the most hesitant on average and Spanish being the least; (c) ChatGPT responses are largely consistent across different model parameters but show some variations across the scale factors (vaccine competency, risk). Results have implications for researchers interested in evaluating and improving the quality and equity of health-related web information.

5.
J Family Med Prim Care ; 13(4): 1354-1361, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38827672

RESUMO

Aim: To analyze the potential predisposing factors and clinical presentation of mucormycosis in patients with COVID-19. Material and Methods: Medical records of 141 patients with COVID-19-associated mucormycosis (CAM) treated at a tertiary care center in Bihar were reviewed. The predisposing factors, clinical features, and imaging findings of mucormycosis were analyzed. Results: The median age was 48 years (IQR, 43-60). A total of 58 patients developed concurrent CAM and 83 post-CAM. The median interval between COVID-19 and onset of CAM symptoms was 15 days (IQR, 9-16). A total of 80 patients received at-home treatment for COVID-19, and 73 had mild-to-moderate disease. While 61 patients received in-hospital treatment, 57 had severe disease. At presentation, 131 patients had hyperglycemia: 64 type 2 diabetes mellitus (DM) and 67 new-onset DM. The history of glucocorticoid use for COVID-19 was present in 125 patients; 47% were administered at home without monitoring plasma glucose. The common presenting features were toothache, periocular or facial pain, and edema. Rhino-orbital mucormycosis was the most common. Imaging revealed rhinosinusitis in all patients, including pansinusitis (68%), pterygopalatine fossa involvement (21%), cavernous sinus thrombosis (38%), brain abscess (8%), and infarct (4%). All patients received intravenous liposomal amphotericin B, and surgical debridement was performed in 113. Conclusion: COVID-19 patients with hyperglycemia are at risk of developing CAM, irrespective of the severity. Timely recognition of symptoms and prompt initiation of therapy by primary healthcare physicians are imperative for enhancing outcomes. Additionally, glucocorticoid overuse should be avoided, and close monitoring for hyperglycemia development is warranted.

6.
PNAS Nexus ; 3(6): pgae191, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38864006

RESUMO

Generative artificial intelligence (AI) has the potential to both exacerbate and ameliorate existing socioeconomic inequalities. In this article, we provide a state-of-the-art interdisciplinary overview of the potential impacts of generative AI on (mis)information and three information-intensive domains: work, education, and healthcare. Our goal is to highlight how generative AI could worsen existing inequalities while illuminating how AI may help mitigate pervasive social problems. In the information domain, generative AI can democratize content creation and access but may dramatically expand the production and proliferation of misinformation. In the workplace, it can boost productivity and create new jobs, but the benefits will likely be distributed unevenly. In education, it offers personalized learning, but may widen the digital divide. In healthcare, it might improve diagnostics and accessibility, but could deepen pre-existing inequalities. In each section, we cover a specific topic, evaluate existing research, identify critical gaps, and recommend research directions, including explicit trade-offs that complicate the derivation of a priori hypotheses. We conclude with a section highlighting the role of policymaking to maximize generative AI's potential to reduce inequalities while mitigating its harmful effects. We discuss strengths and weaknesses of existing policy frameworks in the European Union, the United States, and the United Kingdom, observing that each fails to fully confront the socioeconomic challenges we have identified. We propose several concrete policies that could promote shared prosperity through the advancement of generative AI. This article emphasizes the need for interdisciplinary collaborations to understand and address the complex challenges of generative AI.

7.
Expert Opin Ther Targets ; 28(5): 357-373, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38861226

RESUMO

INTRODUCTION: HIF-1α, a key player in medical science, holds immense significance in therapeutic approaches. This review delves into its complex dynamics, emphasizing the delicate balance required for its modulation. HIF-1α stands as a cornerstone in medical research, its role extending to therapeutic strategies. This review explores the intricate interplay surrounding HIF-1α, highlighting its critical involvement and the necessity for cautious modulation. AREAS COVERED: In sickle cell disease (SCD), HIF-1α's potential to augment fetal hemoglobin (HbF) production and mitigate symptoms is underscored. Furthermore, its role in cancer is examined, particularly its influence on survival in hypoxic tumor microenvironments, angiogenesis, and metastasis. The discussion extends to the intricate relationship between HIF-1α modulation and cancer risks in SCD patients, emphasizing the importance of balancing therapeutic benefits and potential hazards. EXPERT OPINION: Managing HIF-1α modulation in SCD patients requires a nuanced approach, considering therapeutic potential alongside associated risks, especially in exacerbating cancer risks. An evolutionary perspective adds depth, highlighting adaptations in populations adapted to low-oxygen environments and aligning cancer cell metabolism with primitive cells. The role of HIF-1α as a therapeutic target is discussed within the context of complex cancer biology and metabolism, acknowledging varied responses across diverse cancers influenced by intricate evolutionary adaptations.


Assuntos
Anemia Falciforme , Subunidade alfa do Fator 1 Induzível por Hipóxia , Terapia de Alvo Molecular , Neoplasias , Microambiente Tumoral , Humanos , Anemia Falciforme/fisiopatologia , Anemia Falciforme/tratamento farmacológico , Neoplasias/patologia , Neoplasias/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Animais , Hemoglobina Fetal/metabolismo , Neovascularização Patológica
8.
Biomed Phys Eng Express ; 10(5)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38925106

RESUMO

Detecting the Kirsten Rat Sarcoma Virus (KRAS) gene mutation is significant for colorectal cancer (CRC) patients. TheKRASgene encodes a protein involved in the epidermal growth factor receptor (EGFR) signaling pathway, and mutations in this gene can negatively impact the use of monoclonal antibodies in anti-EGFR therapy and affect treatment decisions. Currently, commonly used methods like next-generation sequencing (NGS) identifyKRASmutations but are expensive, time-consuming, and may not be suitable for every cancer patient sample. To address these challenges, we have developedKRASFormer, a novel framework that predictsKRASgene mutations from Haematoxylin and Eosin (H & E) stained WSIs that are widely available for most CRC patients.KRASFormerconsists of two stages: the first stage filters out non-tumor regions and selects only tumour cells using a quality screening mechanism, and the second stage predicts theKRASgene either wildtype' or mutant' using a Vision Transformer-based XCiT method. The XCiT employs cross-covariance attention to capture clinically meaningful long-range representations of textural patterns in tumour tissue andKRASmutant cells. We evaluated the performance of the first stage using an independent CRC-5000 dataset, and the second stage included both The Cancer Genome Atlas colon and rectal cancer (TCGA-CRC-DX) and in-house cohorts. The results of our experiments showed that the XCiT outperformed existing state-of-the-art methods, achieving AUCs for ROC curves of 0.691 and 0.653 on TCGA-CRC-DX and in-house datasets, respectively. Our findings emphasize three key consequences: the potential of using H & E-stained tissue slide images for predictingKRASgene mutations as a cost-effective and time-efficient means for guiding treatment choice with CRC patients; the increase in performance metrics of a Transformer-based model; and the value of the collaboration between pathologists and data scientists in deriving a morphologically meaningful model.


Assuntos
Neoplasias Colorretais , Mutação , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Algoritmos , Receptores ErbB/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Processamento de Imagem Assistida por Computador/métodos , Curva ROC
9.
Pediatr Dermatol ; 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38881098

RESUMO

Musculocontractural Ehlers-Danlos syndrome (MC-EDS) is a rare entity worldwide with underlying pathogenic variant in the carbohydrate sulfotransferase 14 (CHST14) gene. Previous reports of the same entity from India were of two unrelated cases. Ours is the first report of two siblings in an Indian family with craniofacial dysmorphism and distal arthrogryposis with a clinical diagnosis of EDS, where an underlying pathogenic variant in CHST14 was detected by exome sequencing.

10.
Dig Endosc ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695110

RESUMO

Endoscopic ultrasound (EUS) is increasingly used as a therapeutic approach for gastrointestinal diseases, especially with the advent of lumen-apposing metal stents (LAMS). This has led to a rise in of EUS-guided gastrointestinal anastomosis procedures. Due to the reliability of intestinal conduits with LAMS, indications for EUS-guided gastrointestinal anastomosis are becoming more common and trend to potentially be standard care for gastric outlet obstruction, afferent loop syndrome, and EUS-directed transgastric interventions such as EUS-directed endoscopic retrograde cholangiopancreatography. Retrospective and prospective data indicate that the procedure is becoming widely adopted with promising outcomes. This article aims to review the existing literature on EUS-guided gastrointestinal anastomosis and predict its future developments.

11.
J Kidney Cancer VHL ; 11(2): 18-26, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799379

RESUMO

To analyze and compare the intraoperative and post-operative outcomes of "on-clamp" laparoscopic partial nephrectomy (LPN) with "preoperative super-selective angioembolization" before LPN. This randomized clinical study was conducted at Gauhati Medical College Hospital, Guwahati, India, between November 2021 and November 2023. Adult patients of either gender diagnosed with T1 renal tumors were included in the study. All patients underwent diethylenetriamine pentaacetate scan preoperatively and at 1-month follow-up. The patients were randomized using a parallel group design with an allocation ratio of 1:1 to receive either preoperative angioembolization followed by LPN or conventional "on-clamp" LPN. Demographic and baseline parameters were recorded along with pre- and post-operative data. There was no significant difference between the two groups in terms of age (P = 0.11), gender distribution (P = 0.32), body mass index (P = 0.43), preoperative hemoglobin (P = 0.34), and preoperative estimated glomerular filtration rate (eGFR; P = 0.64). One patient in the embolization group required radical nephrectomy because of accidental backflow of glue into the renal artery during embolization whereas four patients required clamping due to inadequate embolization. Preoperative super-selective embolization yielded significantly less blood loss, compared to "on-clamp" LPN (145 [50.76 mL] vs. 261 [66.12 mL], P < 0.01). There was no significant difference between post-operative eGFR (at 1 month) between the two groups (P = 0.71). Preoperative embolization offers improved outcomes in the dissection plane, total operative time, and blood loss, compared to conventional "on-clamp" LPN but has no significant effect on change in eGFR.

12.
3 Biotech ; 14(5): 147, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38706929

RESUMO

In surveys conducted from 2020 to 2022, five leaf samples each from symptomatic Agele marmelos trees and seedlings, along with five samples from asymptomatic trees and seedlings, were collected in Ayodhya, Uttar Pradesh, India. The DNA extraction from all the samples was subjected to nested PCR assays, using the universal phytoplasma-specific primers set (P1/P7 followed by R16F2n/R16R2). The resulting 1.2 kb amplified products were observed in all the symptomatic samples but not in the asymptomatic samples. Bael phytoplasma strain sequences from the trees and seedlings were found 100% identical within themselves and only two representative sequences (one each from tree and seedling) were deposited in GenBank (NCBI) as PP415872 (AmA-1) and PP415873 (AmA-2). BLASTn searches revealed the maximum (100%) sequence identity with a phytoplasma strain from murraya little leaf strain of Faizabad (GenBank Acc.no. OP984129) and lowest (99.84%) with arecanut crown choking of Shimoga (GenBank Acc. no. OM417502) from Karnataka. Phylogenetic analysis clustered the bael phytoplasma isolates with peanut witches' broom group phytoplasma strains. Virtual RFLP analysis confirmed their identity as 'Ca. P. australasiaticum', a 16SrII-D subgroup strain. This study presents the first identification of a phytoplasma strain in A. marmelos, emphasizing its potential threat to fruit crops and the need for vigilance in nursery practices to prevent further dissemination.

13.
Exp Eye Res ; 244: 109949, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38815791

RESUMO

PURPOSE: The current study used various techniques to develop a rabbit animal model of lacrimal gland damage caused by scarring conjunctivitis in the periglandular area. METHODS: Left eyes of New Zealand white rabbits were injected with 0.1 ml of 1M NaOH subconjunctivally around superior and inferior lacrimal gland orifices (Group 1, n = 4), touched with 1M NaOH for 100 s to the superior and inferior fornices with conjunctival denuding (Group 2; n = 4), and electrocauterization to the ductal opening area (Group 3; n = 4). The ocular surface staining, Schirmer I, lacrimal gland, and conjunctival changes were observed at baseline,1, 4, 8, and 12 weeks. The degree of glandular inflammation, conjunctival fibrosis (Masson Trichrome), and goblet cell density (PAS) were also assessed. RESULTS: At 12 weeks, the lacrimal glands of group 1 rabbits with periglandular injection showed severe inflammation with mean four foci/10HPF and a significant mean reduction in the Schirmer values by 7.6 mm (P = 0.007). Lacrimal glands had diffuse acinar atrophy, loss of myoepithelial cells, and ductular dilatation. The overlying conjunctiva showed fibrosis, goblet cell loss, and corneal vascularization in the inferotemporal quadrant. No lacrimal gland or ocular surface changes were observed in groups 2 and 3 at 12 weeks, except for localized subconjunctival fibrosis. CONCLUSION: Periglandular injection of 0.1 ml of 1M NaOH induced extensive lacrimal gland damage with reduced secretion and scarring in the subconjunctival plane compared to direct cauterization or direct NaOH contact to the ductal orifices of the rabbit lacrimal gland.


Assuntos
Cicatriz , Túnica Conjuntiva , Conjuntivite , Modelos Animais de Doenças , Síndromes do Olho Seco , Células Caliciformes , Lágrimas , Animais , Coelhos , Síndromes do Olho Seco/metabolismo , Cicatriz/patologia , Células Caliciformes/patologia , Túnica Conjuntiva/patologia , Lágrimas/metabolismo , Conjuntivite/patologia , Aparelho Lacrimal/patologia , Hidróxido de Sódio/toxicidade , Fibrose , Masculino , Contagem de Células , Feminino , Eletrocoagulação
14.
Nat Commun ; 15(1): 4272, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769321

RESUMO

The mitoribosome translates mitochondrial mRNAs and regulates energy conversion that is a signature of aerobic life forms. We present a 2.2 Å resolution structure of human mitoribosome together with validated mitoribosomal RNA (rRNA) modifications, including aminoacylated CP-tRNAVal. The structure shows how mitoribosomal proteins stabilise binding of mRNA and tRNA helping to align it in the decoding center, whereas the GDP-bound mS29 stabilizes intersubunit communication. Comparison between different states, with respect to tRNA position, allowed us to characterize a non-canonical L1 stalk, and molecular dynamics simulations revealed how it facilitates tRNA transitions in a way that does not require interactions with rRNA. We also report functionally important polyamines that are depleted when cells are subjected to an antibiotic treatment. The structural, biochemical, and computational data illuminate the principal functional components of the translation mechanism in mitochondria and provide a description of the structure and function of the human mitoribosome.


Assuntos
Ribossomos Mitocondriais , RNA de Transferência , Humanos , RNA de Transferência/metabolismo , RNA de Transferência/química , RNA de Transferência/genética , Ribossomos Mitocondriais/metabolismo , Ribossomos Mitocondriais/química , Ligantes , Simulação de Dinâmica Molecular , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Mitocôndrias/metabolismo , RNA Ribossômico/metabolismo , RNA Ribossômico/química , Proteínas Ribossômicas/metabolismo , Proteínas Ribossômicas/química , Guanosina Difosfato/metabolismo , Poliaminas/metabolismo , Poliaminas/química , Ligação Proteica
15.
Bone Joint J ; 106-B(5): 425-429, 2024 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-38689572

RESUMO

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting.


Assuntos
Neoplasias Ósseas , Condrossarcoma , Humanos , Antibioticoprofilaxia , Neoplasias Ósseas/terapia , Neoplasias Ósseas/cirurgia , Condrossarcoma/terapia , Oncologia , Ortopedia , Infecções Relacionadas à Prótese/terapia , Infecções Relacionadas à Prótese/etiologia , Reoperação
16.
Int J Biol Macromol ; 271(Pt 2): 132426, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38820904

RESUMO

Eye-related diseases, specifically retinal dystrophy (RD) conditions, are the leading cause of blindness worldwide. Gene addition, regulation, or editing could potentially treat such diseases through gene expression regulation. CRISPR/Cas9 gene editing is one of the most prominent and precise gene editing tools which could be employed to edit genes related to the dystrophic condition. However, CRISPR/Cas9 faces in vivo delivery challenges due to its high molecular weight, negative charge, prone to degradation in the presence of nucleases and proteases, poor cellular degradation, etc., which makes it challenging to adopt for therapeutic applications. We developed cRGD-modified lipopolymeric nanoplexes loaded with Cas9 RNPs with a particle size and zeta potential of 175 ±â€¯20 nm and 2.15 ±â€¯0.9 mV, respectively. The cRGD-modified lipopolymeric nanoplexes were stable for 194 h and able to transfect >70 % ARPE-19 and NIH3T3 cells with an Indel frequency of ~40 % for the VEGF-A gene. The cRGD-modified lipopolymeric nanoplexes found good vitreous mobility and could transfection retinal cells in vivo after 48 h of intravitreal injection in Wistar Rats. Moreover, in vivo VEGFA gene editing was ~10 % with minimal toxicities. Collectively, the cRGD-modified lipopolymeric nanoplexes were found to have extreme potential in delivering CRISPR/Cas9 RNPs payload to the retinal tissues for therapeutic applications.


Assuntos
Edição de Genes , Animais , Edição de Genes/métodos , Camundongos , Ratos , Humanos , Células NIH 3T3 , Sistemas CRISPR-Cas , Oligopeptídeos/química , Ratos Wistar , Transfecção/métodos , Fator A de Crescimento do Endotélio Vascular/genética , Peptídeos Cíclicos
17.
Gait Posture ; 112: 1-7, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38718437

RESUMO

BACKGROUND: Femoral derotation osteotomy is treatment of choice in intoeing gait secondary to cerebral palsy (CP). RESEARCH QUESTION: The aim of this study was to critically appraise the literature regarding the long-term outcomes of femoral derotation surgery in CP. METHODS: Electronic databases of PubMed and Scopus was used for the literature review by two researchers independently (SB, SC). The study population included patients of cerebral palsy undergoing femoral derotation surgery. The keywords used were "cerebral palsy", "intoeing gait", "femur anteversion", "hip anteversion", "femur derotation" and "femur osteotomy". RESULTS: Nine studies which included 657 limbs in 407 patients were selected for this study of which eight were retrospective in nature. The improvement in hip rotation at stance at last follow up (more than five years) maintained a statistical significance (SMD 1.67 95 %CI 1.12-2.22). Similar statistically significant outcomes were noted for foot progression angle (SMD 1.19 95 %CI 0.92-1.47), anteversion (SMD 2.75 95 %CI 1.49-4.01) and total passive internal rotation (SMD 1.71 95 %CI 1.19-2.22). SIGNIFICANCE: Femoral derotation surgery is the procedure of choice for correction of intoeing gait in CP. Even though, there is deterioration of results on long-term as compared to short term, majority of the patients shall maintain overall correction without recurrence of an intoeing gait. Future studies with uniform criteria for defining recurrence on the basis of functional limitations shall provide better idea about the natural course of this procedure.


Assuntos
Paralisia Cerebral , Fêmur , Transtornos Neurológicos da Marcha , Osteotomia , Paralisia Cerebral/complicações , Paralisia Cerebral/cirurgia , Paralisia Cerebral/fisiopatologia , Humanos , Fêmur/cirurgia , Osteotomia/métodos , Transtornos Neurológicos da Marcha/cirurgia , Transtornos Neurológicos da Marcha/etiologia , Resultado do Tratamento
18.
Chem Asian J ; 19(15): e202400138, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38733617

RESUMO

The aminotroponiminate (ATI) ligand stabilized germylene cation [(i-Bu)2ATIGe][B(C6F5)4] (2) is found to be an efficient low-valent main-group catalyst for the cyanosilylation of aldehydes and ketones (ATI=aminotroponiminate). It was synthesized by reacting [(i-Bu)2ATIGeCl] (1) with Na[B(C6F5)4]. The catalytic cyanosilylation of diverse aliphatic and aromatic carbonyl compounds (aldehydes and ketones) using 0.075-0.75 mol% of compound 2 was completed within 5-45 min. The catalytic efficiency seen with aliphatic aldehydes was around 15,800 h-1, making compound 2 a capable low-valent main-group catalyst for the aldehyde and ketone cyanosilylation reactions. Further, DFT calculations reveal a pronounced charge localization at the germanium atom of compound 2, leading to its superior catalytic performance.

19.
Indian J Otolaryngol Head Neck Surg ; 76(2): 2082-2087, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38566644

RESUMO

Pulsatile tinnitus (PT) is the perception of an auditory sensation without an external source and in synchrony with the heartbeat. One of the most common cases of PT is bony anomalies of the sigmoid sinus, including dehiscence or diverticula. This case report describes a 26-year-old female patient who presented with pulsatile tinnitus caused by sigmoid sinus diverticula and dehiscence, which was successfully treated with cortical mastoidectomy with diverticula closure using pedicled temporalis fascia and resurfacing of the dehiscence with autogenous bone pate along with bone cement. We recommend thorough clinical and radiological workup to rule out other possible causes of PT before surgical intervention. In addition, we would like to highlight the surgical technique using pedicled temporalis fascia that we have used in our patient, which is easily reproducible and offers successful outcomes.

20.
J Orthop Surg (Hong Kong) ; 32(1): 10225536241248706, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38662594

RESUMO

INTRODUCTION: The foot is a complex structure composed of several tissues, each of which can be the origin of the proliferation and development of the tumour. Most lesions about the foot are reactive or inflammatory, but some are true neoplasms. METHOD: This is a retrospective analysis of 4997 patient records treated in the Orthopaedic Oncology Unit of University Malaya Medical Centre, Malaysia, between 1 January 2010 to 31 December 2020. Demographic data of 195 patients with foot tumours were analysed out of 4997 neoplasm patients. RESULTS: There were 195 cases of foot tumours: 148 were benign, and 47 were malignant. 47 were bone tumours, 4 were metastases, and 144 were soft tissue tumours. Six patients succumbed to the disease, two cases of giant cell tumour (GCT) and one patient with synovial sarcoma had a recurrence. Treatment of foot tumours was wide resection in general. However, in metastasis cases, amputation was done. The majority of tumours were in the toes and dorsum of the foot. Soft tissue tumours of the foot occur in the elderly population in contrast to bone tumours, mainly in the second decade of life. The gender distribution was almost equal for foot tumours. Ganglion and Giant Cell Tumour of the bone are the commonest benign soft tissue and bone tumours. The most common malignant soft tissue and bone tumours are malignant melanoma and chondrosarcoma. The amputation rate is 5.64% the recurrence rate is 1.54%. Mortality rate is 3.08%. The MSTS score is 79%, and the TESS score is 76.23%. CONCLUSION: Foot tumours are relatively rare, mostly originating from soft tissue and exhibiting a benign nature. Nonetheless, a noteworthy proportion-approximately a quarter of these tumours-demonstrate malignancy. The surgical interventions undertaken in managing these tumours and associated functional outcomes generally yield acceptable results.


Assuntos
Neoplasias Ósseas , Neoplasias de Tecidos Moles , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/terapia , Neoplasias de Tecidos Moles/cirurgia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/terapia , Neoplasias Ósseas/patologia , Idoso , Malásia/epidemiologia , Adolescente , Adulto Jovem , Criança , Pé/cirurgia , Amputação Cirúrgica/estatística & dados numéricos , Idoso de 80 Anos ou mais , Doenças do Pé/cirurgia , Doenças do Pé/patologia , Doenças do Pé/terapia , Pré-Escolar
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