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1.
BMC Ophthalmol ; 24(1): 135, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532334

RESUMO

BACKGROUND: Epithelial ingrowth is a rare but potentially sight-threatening complication caused by the invasion of corneal or conjunctival epithelial cells into the eye during ocular surgeries. DMEK is emerging as a widely used surgery for endothelial keratoplasty with its improved safety profile. We describe a case of epithelial ingrowth in the graft-host interface after uneventful DMEK associated with vitreous prolapse in the anterior chamber. CASE PRESENTATION: An 81-year-old female with Fuchs endothelial dystrophy underwent DMEK for corneal decompensation following cataract surgery. During the DMEK procedure, vitreous prolapse was observed around the intraocular lens (IOL). Her early postoperative course was unremarkable, but a dense paracentral interface opacity was observed during the 3-month follow-up. The area of epithelial ingrowth was imaged with optical coherence tomography (OCT) as a uniform nodule with a discrete increase in interface hyperreflectivity. A low-energy YAG laser was applied to remove the opacity. She maintained good vision and clear cornea without reoccurrence after treatment. CONCLUSIONS: We propose that, in addition to the introduction of epithelial cells during surgery, vitreous retention in the anterior chamber may be a risk factor by providing a scaffold that potentially aggravates epithelial ingrowth in DMEK. Our case demonstrated that early YAG intervention may disrupt interface epithelial cell growth, and the transmitted laser energy may fragment the scaffold vitreous noninvasively.


Assuntos
Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Distrofia Endotelial de Fuchs , Humanos , Feminino , Idoso de 80 Anos ou mais , Lâmina Limitante Posterior/cirurgia , Endotélio Corneano , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Complicações Pós-Operatórias/cirurgia , Distrofia Endotelial de Fuchs/cirurgia , Transtornos da Visão , Prolapso , Estudos Retrospectivos
2.
J Minim Access Surg ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36124469

RESUMO

Intra-peritoneal migration of abdominal drain is a rare complication. Cutting of abdominal drain and putting a colostomy bag over it is done to reduce the pain and infection and to increase the mobility of a patient, but it is also a risk factor for drain intra-peritoneal migration. This case report depicts a case of intra-peritoneal migration of abdominal drain after laparoscopic cholecystectomy and its retrieval.

3.
Hum Mutat ; 42(10): 1336-1350, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34273913

RESUMO

Pathogenic variations in SMPD1 lead to acid sphingomyelinase deficiency (ASMD), that is, Niemann-Pick disease (NPD) type A and B (NPA, NPB), which is a recessive lysosomal storage disease. The knowledge of variant spectrum in Indian patients is crucial for early and accurate NPD diagnosis and genetic counseling of families. In this study, we recruited 40 unrelated pediatric patients manifesting symptoms of ASMD and subnormal ASM enzyme activity. Variations in SMPD1 were studied using Sanger sequencing for all exons, followed by interpretation of variants based on American College of Medical Genetics and Genomics & Association for Molecular Pathology (ACMG/AMP) criteria. We identified 18 previously unreported variants and 21 known variants, including missense, nonsense, deletions, duplications, and splice site variations with disease-causing potential. Eight missense variants were functionally characterized using in silico molecular dynamic simulation and in vitro transient transfection in HEK293T cells, followed by ASM enzyme assay, immunoblot, and immunofluorescence studies. All the variants showed reduced ASM activity in transfected cells confirming their disease-causing potential. The study provides data for efficient prenatal diagnosis and genetic counseling of families with NPD type A and B.


Assuntos
Doença de Niemann-Pick Tipo A , Doenças de Niemann-Pick , Esfingomielina Fosfodiesterase/genética , Criança , Éxons , Feminino , Células HEK293 , Humanos , Mutação , Doença de Niemann-Pick Tipo A/genética , Doença de Niemann-Pick Tipo A/patologia , Doenças de Niemann-Pick/diagnóstico , Doenças de Niemann-Pick/genética , Gravidez
4.
Microbiology (Reading) ; 164(9): 1133-1145, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29993358

RESUMO

Lipid metabolism is critical to Mycobacterium tuberculosis survival and infection. Unlike Escherichia coli, which has a single FadR, the M. tuberculosis genome encodes five proteins of the FadR sub-family. While the role of E. coli FadR as a regulator of fatty acid metabolism is well known, the definitive functions of M. tuberculosis FadR proteins are still under investigation. An interesting question about the M. tuberculosis FadRs remains open: which one of these proteins is the functional homologue of E. coli FadR? To address this, we have applied two different approaches. The first one was the bioinformatics approach and the second one was the classical molecular genetic approach involving complementation studies. Surprisingly, the results of these two approaches did not agree. Among the five M. tuberculosis FadRs, Rv0494 shared the highest sequence similarity with FadRE. coli and Rv0586 was the second best match. However, only Rv0586, but not Rv0494, could complement E. coli ∆fadR, indicating that Rv0586 is the M. tuberculosis functional homologue of FadRE. coli. Further studies showed that both regulators, Rv0494 and Rv0586, show similar responsiveness to LCFA, and have conserved critical residues for DNA binding. However, analysis of the operator site indicated that the inter-palindromic distance required for DNA binding differs for the two regulators. The differences in the binding site selection helped in the success of Rv0586 binding to fadB upstream over Rv0494 and may have played a critical role in complementing E. coli ∆fadR. Further, for the first time, we report the lipid-responsive nature of Rv0586.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Metabolismo dos Lipídeos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Biologia Computacional , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica , Teste de Complementação Genética , Proteínas Repressoras/deficiência , Homologia de Sequência de Aminoácidos
5.
Cureus ; 16(5): e60706, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38899251

RESUMO

Innovative applications of clinical ocular diagnostic tools are emerging to help identify systemic disorders that extend beyond ocular diseases. Ophthalmodynamometry (ODM) is a screening tool that non-invasively determines mean central retinal artery pressure (MCRAP) and ocular perfusion pressure (OPP). Decreased OPP and MCRAP on Falck Medical Multifunctional Device (FMD, Falck Medical, Inc., Mystic, CT), along with reverse ophthalmic artery flow (ROAF) on transcranial Doppler ultrasonography (TCD), indicate increased collateral brain perfusion and possible stenosis of the ophthalmic artery or internal carotid artery (ICA). In this case report, we describe the case of a 78-year-old female with ROAF, reduced MCRAP, and OPP in the right eye, confirmed by carotid duplex of 50-79% right ICA stenosis. Early application of ODM and TCD allowed for prompt diagnosis and management with a vascular specialist.

6.
Curr Med Imaging ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38721793

RESUMO

BACKGROUND: Early disease detection is emphasized within ophthalmology now more than ever, and as a result, clinicians and innovators turn to deep learning to expedite accurate diagnosis and mitigate treatment delay. Efforts concentrate on the creation of deep learning systems that analyze clinical image data to detect disease-specific features with maximum sensitivity. Moreover, these systems hold promise of early accurate diagnosis and treatment of patients with common progressive diseases. DenseNet, ResNet, and VGG-16 are among a few of the deep learning Convolutional Neural Network (CNN) algorithms that have been introduced and are being investigated for potential application within ophthalmology. METHODS: In this study, the authors sought to create and evaluate a novel ensembled deep learning CNN model that analyzes a dataset of shuffled retinal color fundus images (RCFIs) from eyes with various ocular disease features (cataract, glaucoma, diabetic retinopathy). Our aim was to determine (1) the relative performance of our finalized model in classifying RCFIs according to disease and (2) the diagnostic potential of the finalized model to serve as a screening test for specific diseases (cataract, glaucoma, diabetic retinopathy) upon presentation of RCFIs with diverse disease manifestations. RESULTS: We found adding convolutional layers to an existing VGG-16 model, which was named as a proposed model in this article that, resulted in significantly increased performance with 98% accuracy (p<0.05), including good diagnostic potential for binary disease detection in cataract, glaucoma, diabetic retinopathy. CONCLUSION: The proposed model was found to be suitable and accurate for a decision support system in Ophthalmology Clinical Framework.

7.
J Curr Glaucoma Pract ; 18(1): 28-30, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585167

RESUMO

Aim and background: Combined endocyclophotocoagulation and phacoemulsification (ECP/Phaco) are uncommonly associated with complications. We present the first case of a rare complication following ECP/Phaco. Case description: A 72-year-old patient with dense nuclear sclerotic cataracts and primary open-angle glaucoma (POAG) underwent bilateral surgery uneventfully. He experienced a brief episode of postoperative elevated intraocular pressure (IOP), but only one eye with a lower baseline IOP developed a dilated pupil. No pupillary response was observed after applying 4% pilocarpine. The fixed mydriasis persisted without reaction to light or near stimulus, and the best-corrected vision (BCVA) was 20/30 in the affected eye. Conclusion: This case reports a possible rare complication when undergoing ECP/Phaco therapy. The pathogenesis of Urrets-Zavalia syndrome is unknown, but we hypothesized that eyes with more pronounced increases in IOP from baseline may be more susceptible to ischemic injury to the pupillary sphincter, resulting in a chronically dilated pupil. Clinical significance: Even a modest transient rise in postoperative IOP in a glaucomatous eye with normal baseline IOP could result in a chronically dilated pupil. How to cite this article: Cheng AMS, Vedula GG, Kubal AA, et al. Urrets-Zavalia Syndrome of Unresolving Mydriasis Following Endocyclophotocoagulation Combined with Phacoemulsification. J Curr Glaucoma Pract 2024;18(1):28-30.

8.
J Pediatr Genet ; 12(4): 325-328, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38162161

RESUMO

Galactosialidosis (GS) is a rare lysosomal storage disorder. We reported here, the case of a 29-day-old boy who had increased body swelling, difficulty breathing, and petechiae on the trunk since birth. The antenatal history was unremarkable. Clinical laboratory findings included coarse facies, hepatosplenomegaly, gross ascites, thrombocytopenia, nephrotic range proteinuria, and bilateral hydronephrosis. The diagnostic challenge was resolved after genetic testing, which revealed GS with a novel homozygous c.1158dupA mutation.

9.
Cureus ; 15(2): e34830, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36919069

RESUMO

BACKGROUND: Urinary tract infection (UTI) is one of the most commonly encountered bacterial infections. Due to the misuse or excessive use of antibiotics, the upsurge of multidrug-resistance cases in UTIs has now become a global threat to public health. Exploring a newer or safer treatment using green synthesized nanoparticles (NPs) is another substitute for eliminating multidrug-resistant pathogens. METHODOLOGY: Leaf extract of Syzygium cumini was used for green synthesis of gold NPs. Synthesis of Syzygium cumini gold nanoparticles (ScAu-NPs) was achieved by optimizing various reaction parameters. These ScAu-NPs were characterized through UV-visible spectroscopy, transmission electron microscope, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction. ScAu-NPs were then processed for antibacterial activity against clinically isolated multidrug-resistant pathogens like Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Acinetobacter baumannii, Staphylococcus aureus, and Enterococcus faecalis. RESULTS: Characterization of NPs revealed that biosynthesized NPs were spherical in shape. FTIR spectroscopy showed the presence of phenolics and aromatic compounds. Biosynthesized NPs exhibit good antibacterial activity with a significant bacterial reduction seen against all bacterial isolates compared to the controls. CONCLUSION: From the results of the present study, the formulation of biosynthesized ScAu-NPs can be utilized in drug development for eliminating infections caused by multidrug-resistant pathogens.

10.
Int Med Case Rep J ; 16: 419-423, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37469851

RESUMO

When non-glaucomatous disease with disc cupping mimics normal-tension glaucoma (NTG), diagnosis is challenging. The typical optic disc features of glaucomatous disease are often subjective, and often overlap with disc changes in compressive intracranial lesions. Ancillary diagnostic testing such as retinal nerve fiber layer (RNFL) analysis and visual field testing can elevate the index of suspicion of an underlying non-glaucomatous process. We present a case of a nonfunctional macroadenoma coexisting with NTG, although it is unclear if the concurrent brain lesion aggravated or caused it. This case highlights the diagnostic challenge of recognizing optic cupping and non-matching abnormalities in the visual field from a coexisting intracranial lesion, even in the absence of other neurological signs.

11.
Front Microbiol ; 14: 1279632, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38298537

RESUMO

India had faced three waves throughout the Coronavirus disease 2019 (COVID-19) pandemic, which had already impacted economic lives and affected the healthcare setting and infrastructure. The widespread impacts have inspired researchers to look for clinical indicators of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection prognosis. Cyclic threshold values have been used to correlate the viral load in COVID-19 patients and for viral transmission. In light of this correlation, a retrospective study was conducted to assess the trend of viral load in clinical and demographic profiles across the three waves. Data of a total of 11,125 COVID-19-positive patients were obtained, which had a Ct value of <35. We stratified Ct values as follows: under 25 (high viral load), 25-30 (moderate viral load), and over 30 (low viral load). We found a significantly high proportion of patients with high viral load during the second wave. A significantly high viral load across the symptomatic and vaccinated populations was found in all three waves, whereas a significantly high viral load across age groups was found only in the first wave. With the widespread availability of real-time PCR and the limited use of genomic surveillance, the Ct value and viral load could be a suitable tool for population-level monitoring and forecasting.

12.
Cureus ; 15(3): e36215, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37069862

RESUMO

Introduction The second wave of the coronavirus disease 2019 (COVID-19) pandemic in India, which started from April 2021, has been more severe and deadly than the first wave. The aim of this prospective study was to determine the possibility of other respiratory pathogens contributing towards the severity and hospitalization in the current second wave. Materials and methods Nasopharyngeal and oropharyngeal swab samples were collected and processed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription polymerase chain reaction (RT-PCR). These samples were further processed for detection of co-infection in SARS CoV-2 patients by BioFire® Filmarray® 2.0 (bioMérieux, USA). Results We screened 77 COVID-19-positive patients admitted to All India Institute of Medical Sciences (AIIMS), Rishikesh and found cases of co-infections in five (6.49 %) patients. Conclusion Our finding suggests that co-infections had no or minimal role in augmenting the second wave of the COVID-19 pandemic in India, and the emergence of new variants may be the probable cause.

13.
Diagnostics (Basel) ; 13(24)2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38132220

RESUMO

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. In late-stage AMD, geographic atrophy (GA) of dry AMD or choroidal neovascularization (CNV) of neovascular AMD eventually results in macular atrophy (MA), leading to significant visual loss. Despite the development of innovative therapies, there are currently no established effective treatments for MA. As a result, early detection of MA is critical in identifying later central macular involvement throughout time. Accurate and early diagnosis is achieved through a combination of clinical examination and imaging techniques. Our review of the literature depicts advances in retinal imaging to identify biomarkers of progression and risk factors for late AMD. Imaging methods like fundus photography; dye-based angiography; fundus autofluorescence (FAF); near-infrared reflectance (NIR); optical coherence tomography (OCT); and optical coherence tomography angiography (OCTA) can be used to detect and monitor the progression of retinal atrophy. These evolving diverse imaging modalities optimize detection of pathologic anatomy and measurement of visual function; they may also contribute to the understanding of underlying mechanistic pathways, particularly the underlying MA changes in late AMD.

14.
Surg Neurol Int ; 14: 290, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37680917

RESUMO

Background: Cerebral autoregulation (CA) is crucial for the maintenance of cerebral homeostasis. It can be assessed by measuring transient hyperemic response ratio (THRR) using transcranial Doppler (TCD). We aimed at assessing the incidence of impaired CA (ICA) and its correlation with the neurological outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods: One hundred consecutive patients with aSAH scheduled for aneurysmal clipping were enrolled in this prospective and observational study. Preoperative and consecutive 5-day postoperative THRR measurements were taken. Primary objective of the study was to detect the incidence of ICA and its correlation with vasospasm (VS) postclipping, and neurological outcome at discharge and 1, 3, and 12 months was secondary objectives. Results: ICA (THRR < 1.09) was observed in 69 patients preoperatively, 74 patients on the 1st and 2nd postoperative day, 76 patients on 3rd postoperative day, and 78 patients on 4th and 5th postoperative day. Significant VS was seen in 13.4% and 61.5% of patients with intact THRR and deranged THRR, respectively (P < 0.000). Out of 78 patients who had ICA, 42 patients (53.8%) at discharge, 60 patients (76.9%) at 1 month, 54 patients (69.2%) at 3 month, and 55 patients (70.5%) at 12 months had unfavorable neurological outcome significantly more than those with preserved CA. Conclusion: Incidence of ICA assessed in aSAH patients varies from 69% to 78% in the perioperative period. The deranged CA was associated with significantly poor neurological outcome. Therefore, CA assessment using TCD-based THRR provides a simple, noninvasive bedside approach for predicting neurological outcome in aSAH.

15.
Artigo em Inglês | MEDLINE | ID: mdl-36249091

RESUMO

In the present paper, our model consists of deep learning approach: DenseNet201 for detection of COVID and Pneumonia using the Chest X-ray Images. The model is a framework consisting of the modeling software which assists in Health Insurance Portability and Accountability Act Compliance which protects and secures the Protected Health Information . The need of the proposed framework in medical facilities shall give the feedback to the radiologist for detecting COVID and pneumonia though the transfer learning methods. A Graphical User Interface tool allows the technician to upload the chest X-ray Image. The software then uploads chest X-ray radiograph (CXR) to the developed detection model for the detection. Once the radiographs are processed, the radiologist shall receive the Classification of the disease which further aids them to verify the similar CXR Images and draw the conclusion. Our model consists of the dataset from Kaggle and if we observe the results, we get an accuracy of 99.1%, sensitivity of 98.5%, and specificity of 98.95%. The proposed Bio-Medical Innovation is a user-ready framework which assists the medical providers in providing the patients with the best-suited medication regimen by looking into the previous CXR Images and confirming the results. There is a motivation to design more such applications for Medical Image Analysis in the future to serve the community and improve the patient care.

16.
J Neurosurg Anesthesiol ; 34(4): 407-414, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33835084

RESUMO

BACKGROUND: Fluid imbalance is common after aneurysmal subarachnoid hemorrhage and negatively impacts clinical outcomes. We compared intraoperative goal-directed fluid therapy (GDFT) using left ventricular outflow tract velocity time integral (LVOT-VTI) measured by transesophageal echocardiography with central venous pressure (CVP)-guided fluid therapy during aneurysm clipping in aneurysmal subarachnoid hemorrhage patients. METHODS: Fifty adults scheduled for urgent craniotomy for aneurysm clipping were randomly allocated to 2 groups: group G (n=25) received GDFT guided by LVOT-VTI and group C (n=25) received CVP-guided fluid management. The primary outcome was intraoperative mean arterial pressure (MAP). Secondary outcomes included volume of fluid administered and several other intraoperative and postoperative variables, including neurological outcome at hospital discharge and at 30 and 90 days. RESULTS: There was no difference in MAP between the 2 groups despite patients in group G receiving lower volumes of fluid compared with patients in group C (2503.6±534.3 vs. 3732.8±676.5 mL, respectively; P <0.0001). Heart rate and diastolic blood pressure were also comparable between groups, whereas systolic blood pressure was higher in group G than in group C at several intraoperative time points. Other intraoperative variables, including blood loss, urine output, and lactate levels were not different between the 2 groups. Postoperative variables, including creatinine, duration of postoperative mechanical ventilation, length of intensive care unit and hospital stay, and incidence of acute kidney injury, pneumonitis, and vasospasm were also comparable between groups. There was no difference in neurological outcome at hospital discharge (modified Rankin scale) and at 30 and 90 days (Extended Glasgow Outcome Scale) between the 2 groups. CONCLUSION: Compared with CVP-guided fluid therapy, transesophageal echocardiography-guided GDFT maintains MAP with lower volumes of intravenous fluid in patients undergoing clipping of intracranial aneurysms with no adverse impact on postoperative complications.


Assuntos
Aneurisma Intracraniano , Hemorragia Subaracnóidea , Adulto , Craniotomia , Hidratação , Objetivos , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/cirurgia , Estudos Prospectivos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/cirurgia
17.
Autoimmune Dis ; 2022: 1343805, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338545

RESUMO

Background: Indirect immunofluorescence assay (IIFA) based on antineutrophil cytoplasmic antibody (ANCA) testing is a commonly employed test for diagnosing autoimmune vasculitis. Antinuclear antibody (ANA) can give rise to a false interpretation of perinuclear-ANCA (pANCA) in ethanol-fixed granulocyte substrates. Analytical interference could frequently occur in setups where ethanol-fixed substrates are used alone. Here, we intend to investigate this ANA interference in pANCA interpretation. Methods: In this retrospective study, we studied anti-MPO-negative but ANA-positive and pANCA (IIFA based) samples. We also correlated immunoblot results (where data were available) and checked the association between grades of blot positivity (an indicator of the concentration of ANA) and frequency of pANCA interpretation. Data were analyzed by appropriate statistical techniques (Chi-square and kappa statistics). Results: About 19.2% of ANA blot (ENA-blot) positive samples displayed a pANCA positive pattern in the ethanol-fixed substrate, while this positivity in ENA-blot negatives was 6.5%. In positive ANA-IIFA samples, about 14.7% yielded pANCA patterns (on ethanol fixed substrates). Out of this, nuclear homogenous pattern yielding samples gave the highest frequency pANCA, that is, in 31.5% followed by speckled (11.1%), DFS (10.3%), and centromere (6.7%).The association of the nuclear homogenous pattern was statistically significant. Conclusions: ANA-positive results may interfere with the interpretation of pANCA as observed in ANA-IIFA and ENA-blot positive samples. ANA-IIFA patterns like nuclear homogenous may strongly associate this pANCA interpretation. This can help laboratories perform ANCA testing more effectively, ruling out ANA interference in ANCA screening.

18.
J Neurosci ; 30(7): 2755-66, 2010 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-20164359

RESUMO

Successful axon targeting during development is critically dependent on directionality of axon extension and requires coordination between the extrinsic cues that provide spatial information to the axon and the intrinsic responses that regulate structural specification of the axon during neuronal polarization. How these responses are coordinated is unclear but are known to involve aligning the centrosome with the base of the emerging axon. We have used a novel in vitro micropatterning assay that spatially segregates the extrinsic cues used by polarizing cerebellar granule cells to orient axon extension and used it to investigate the signaling mechanisms responsible for coordinating centrosome positioning with intrinsic responses. The results show that, when laminin and/or vitronectin are used as spatially restricted cues in association with substrate-associated sonic hedgehog, they are sufficient to induce cell cycle arrest, that laminin and vitronectin then induce integrin-mediated signaling that upregulates phosphoinositide-3 kinase and PKC function to produce phosphatidylinositol 3,4,5-trisphosphate (PIP3) that is associated with the centrosome, that this PIP3 can interact with PKC-phosphorylated growth-associated protein GAP-43, and that PKC-phosphorylated GAP-43 in turn is required for positioning Par6, Cdc42, and IQGAP1, all intrinsic response components, in proximity to the centrosome, such that, in the absence of GAP-43, they are mislocalized and microtubules are not oriented appropriately. We conclude from these results that GAP-43 plays an important role in coordinating extrinsic signaling and intrinsic responses in polarizing cerebellar granule neurons.


Assuntos
Centrossomo/fisiologia , Cerebelo/citologia , Matriz Extracelular/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Neurônios/citologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Análise de Variância , Animais , Animais Recém-Nascidos , Células Cultivadas , Cerebelo/crescimento & desenvolvimento , Embrião de Mamíferos , Proteína GAP-43/genética , Proteína GAP-43/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Técnicas In Vitro , Laminina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas do Tecido Nervoso/metabolismo , Neurônios/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Ligação Proteica/genética , Proteína Quinase C/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/fisiologia , Vitronectina/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo , Proteínas Ativadoras de ras GTPase/metabolismo
19.
Surg Neurol Int ; 12: 92, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33767896

RESUMO

BACKGROUND: Manipulation during endotracheal intubation in patients with craniovertebral junction (CVJ) anomalies may cause neurological deterioration due to underlying instability. Fiberoptic-bronchoscopy (FOB) is better than video laryngoscope (VL) for minimizing cervical spine movement during intubation. However, evidence suggesting superiority of FOB in patients with CVJ instability is lacking. We prospectively compared dynamic movements of the upper cervical spine during intubation using FOB with VL in patients with CVJ anomalies. METHODS: A prospective, randomized, and clinical trial was conducted in 62 patients of American Society of Anaesthesiologist Grade I-II aged between 12 and 65 years with CVJ anomalies. Patients were randomized for intubation under general anesthesia with either VL or FOB. The intubation process was done with application of skeletal traction and recorded cinefluroscopically. The dynamic interrelationship of bony landmarks (horizontal, vertical, and diagonal distances between fixed points on posterior C1 and C2) was analyzed to indirectly calculate alteration of the upper cervical spinal canal diameter (at CVJ). Atlanto-dental interval (ADI) was calculated wherever possible. RESULTS: The alteration in canal diameter (using bony landmarks) at CVJ during intubation was not significant with the use of either VL or FOB (P > 0.05). In 41 patients, where ADI could be measured, ADI was reduced (increased spinal canal diameter) in a greater number of patients in VL group when compared to FOB group (P < 0.05). CONCLUSION: Using rigid skull traction, intubation under general anesthesia with VL offers similar advantage as FOB in terms of the spinal kinematics in patients with CVJ anomalies/instability. Nevertheless, greater number of patients intubated with VL may have an advantage of increased cervical spinal canal diameter when compared to FOB.

20.
Sci Rep ; 11(1): 11575, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078926

RESUMO

The renal proximal tubule is responsible for re-absorption of the majority of the glomerular filtrate and its proper function is necessary for whole-body homeostasis. Aging, certain diseases and chemical-induced toxicity are factors that contribute to proximal tubule injury and chronic kidney disease progression. To better understand these processes, it would be advantageous to generate renal tissues from human induced pluripotent stem cells (iPSC). Here, we report the differentiation and characterization of iPSC lines into proximal tubular-like cells (PTL). The protocol is a step wise exposure of small molecules and growth factors, including the GSK3 inhibitor (CHIR99021), the retinoic acid receptor activator (TTNPB), FGF9 and EGF, to drive iPSC to PTL via cell stages representing characteristics of early stages of renal development. Genome-wide RNA sequencing showed that PTL clustered within a kidney phenotype. PTL expressed proximal tubular-specific markers, including megalin (LRP2), showed a polarized phenotype, and were responsive to parathyroid hormone. PTL could take up albumin and exhibited ABCB1 transport activity. The phenotype was stable for up to 7 days and was maintained after passaging. This protocol will form the basis of an optimized strategy for molecular investigations using iPSC derived PTL.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Túbulos Renais Proximais/citologia , Biomarcadores/metabolismo , Diferenciação Celular , Células Cultivadas , Humanos , Análise de Sequência de RNA/métodos
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