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1.
Opt Express ; 32(8): 13769-13782, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859338

RESUMO

During sub-optimal weather, a free-space optical (FSO) link range degrades depending on attenuation (atmospheric extinction) and turbulence effects. The ability to predict the system level performance can be exceedingly challenging as the atmospheric variability in a maritime link can be large and difficult to model. Link budget estimation for FSO systems often takes a nominal view of atmospheric conditions; here, we use statistical atmospheric predictions specific to a geographic area of interest to enable performance trades to be evaluated through link budget analysis. We compare these models to field-collected data to show the utility of the statistical atmospheric analysis in predicting FSO link performance for specific parts of the world. We have performed shore-to-ship FSO communications field tests at 10 Gb/s with links reaching out to a horizon limit over 40 km away in times of moderate extinction to clear weather. We provide further analysis by describing the expected performance of the link using statistical probabilities via cumulative distribution functions of both extinction and turbulence. The atmospheric variability can be determined for nearly any region of interest through the implementation of numerical weather prediction data to calculate the atmospheric performance drivers. These conditions are specifically evaluated for the 2017 Trident Warrior field test off the coast of San Diego, California, USA.

2.
Acta Neurochir Suppl ; 130: 81-84, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37548726

RESUMO

An unexpected rupture at the aneurysm neck, with or without adjacent arterial injury or compromise of distal branches during microsurgical clipping, can be a challenging surgical problem to resolve. In this presented case of a neurologically intact 65-year-old woman, elective clipping of an unruptured right middle cerebral artery bifurcation aneurysm was complicated by an unexpected M2 tear at the neck, involving the origin of the frontal M2. Attempts to seal the tear directly, using various techniques, failed; therefore, it was ultimately managed with sacrifice of the vessel and a salvage side-to-side M2-to-M2 in situ bypass. Six months after surgery, the patient demonstrated moderate disability but was able to ambulate with a cane.


Assuntos
Revascularização Cerebral , Aneurisma Intracraniano , Feminino , Humanos , Idoso , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/complicações , Procedimentos Neurocirúrgicos/métodos , Revascularização Cerebral/métodos , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/cirurgia
3.
Acta Neurochir (Wien) ; 165(2): 451-459, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36220949

RESUMO

PURPOSE: Due to the risk of intracranial aneurysm (IA) recurrence and the potential requirement for re-treatment following endovascular treatment (EVT), radiological follow-up of these aneurysms is necessary. There is little evidence to guide the duration and frequency of this follow-up. The aim of this study was to establish the current practice in neurosurgical units in the UK and Ireland. METHODS: A survey was designed with input from interventional neuroradiologists and neurosurgeons. Neurovascular consultants in each of the 30 neurosurgical units providing a neurovascular service in the UK and Ireland were contacted and asked to respond to questions regarding the follow-up practice for IA treated with EVT in their department. RESULTS: Responses were obtained from 28/30 (94%) of departments. There was evidence of wide variations in the duration and frequency of follow-up, with a minimum follow-up duration for ruptured IA that varied from 18 months in 5/28 (18%) units to 5 years in 11/28 (39%) of units. Young patient age, previous subarachnoid haemorrhage and incomplete IA occlusion were cited as factors that would prompt more intensive surveillance, although larger and broad-necked IA were not followed-up more closely in the majority of departments. CONCLUSIONS: There is a wide variation in the radiological follow-up of IA treated with EVT in the UK and Ireland. Further standardisation of this aspect of patient care is likely to be beneficial, but further evidence on the behaviour of IA following EVT is required in order to inform this process.


Assuntos
Aneurisma Roto , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Seguimentos , Irlanda , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/cirurgia , Embolização Terapêutica/métodos , Aneurisma Roto/cirurgia , Reino Unido , Resultado do Tratamento
4.
Br J Neurosurg ; 37(2): 163-169, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34738491

RESUMO

OBJECTIVE: Unruptured intracranial aneurysms (UIA) are common. For many the treatment risks outweigh their risk of subarachnoid haemorrhage and patients undergo surveillance imaging. There is little data to inform if and how to monitor UIAs resulting in widely varying practices. This study aimed to determine the current practice of unruptured UIA surveillance in the United Kingdom. METHODS: A questionnaire was designed to address the themes of surveillance protocols for UIA including when surveillance is initiated, how frequently it is performed, and when it is terminated. Additionally, how aneurysm growth is managed and how clinically meaningful growth is defined were explored. The questionnaire was distributed to members of the British Neurovascular Group using probability-based cluster and non-probability purposive sampling methods. RESULTS: Responses were received from 30 of the 30 (100.0%) adult neurosurgical units in the United Kingdom of which 27 (90.0%) routinely perform surveillance for aneurysm growth. Only four units had a unit policy. The mean patient age up to which a unit would initiate follow-up of a low-risk UIA was 65.4 ± 9.0 years. The time points at which imaging is performed varied widely. There was an even split between whether units use a fixed duration of follow-up or an age threshold for terminating surveillance. Forty percent of units will follow-up patients more than 5 years from diagnosis. The magnitude in the change in size that was felt to constitute growth ranged from 1 to 3mm. No units routinely used vessel wall imaging although 27 had access to 3T MRI capable of performing it. CONCLUSIONS: There is marked heterogeneity in surveillance practices between units in the United Kingdom. This study will help units better understand their practice relative to their peers and provide a framework forplanning further research on aneurysm growth.


Assuntos
Aneurisma Intracraniano , Hemorragia Subaracnóidea , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Seguimentos , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/cirurgia , Reino Unido , Inquéritos e Questionários
5.
Molecules ; 28(13)2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37446749

RESUMO

This paper describes the three-step synthesis of TBS-MAC, a masked acyl cyanide (MAC) and a versatile one-carbon oxidation state three synthon. We have developed a scalable and detailed synthesis that involves: (1) acetylation of malononitrile to form the sodium enolate, (2) protonation of the enolate to form acetylmalononitrile, and (3) epoxidation of the enol, rearrangement to an unstable alcohol, and TBS-protection to form the title compound. Both the sodium enolate and acetylmalononitrile are bench-stable precursors to the intermediate hydroxymalononitrile, which can be converted to other MAC reagents beyond TBS by varying the protecting group (Ac, MOM, EE, etc.).


Assuntos
Ácidos Carboxílicos , Cianetos , Álcoois , Sódio
6.
J Biol Chem ; 296: 100363, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33539919

RESUMO

During the integration step, human immunodeficiency virus type 1 integrase (IN) interacts with viral DNA and the cellular cofactor LEDGF/p75 to effectively integrate the reverse transcript into the host chromatin. Allosteric human immunodeficiency virus type 1 integrase inhibitors (ALLINIs) are a new class of antiviral agents that bind at the dimer interface of the IN catalytic core domain and occupy the binding site of LEDGF/p75. While originally designed to block IN-LEDGF/p75 interactions during viral integration, several of these compounds have been shown to also severely impact viral maturation through an IN multimerization mechanism. In this study, we tested the hypothesis that these dual properties of ALLINIs could be decoupled toward late stage viral replication effects by generating additional contact points between the bound ALLINI and a third subunit of IN. By sequential derivatization at position 7 of a quinoline-based ALLINI scaffold, we show that IN multimerization properties are enhanced by optimizing hydrophobic interactions between the compound and the C-terminal domain of the third IN subunit. These features not only improve the overall antiviral potencies of these compounds but also significantly shift the ALLINIs selectivity toward the viral maturation stage. Thus, we demonstrate that to fully maximize the potency of ALLINIs, the interactions between the inhibitor and all three IN subunits need to be simultaneously optimized.


Assuntos
Integrase de HIV/metabolismo , HIV-1/metabolismo , Quinolinas/farmacologia , Regulação Alostérica/efeitos dos fármacos , Antivirais/farmacologia , Células HEK293 , Integrase de HIV/fisiologia , Inibidores de Integrase de HIV/metabolismo , Inibidores de Integrase de HIV/farmacologia , HIV-1/efeitos dos fármacos , HIV-1/patogenicidade , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Modelos Moleculares , Ligação Proteica/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos , Quinolinas/química , Quinolinas/metabolismo , Integração Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
7.
Drug Dev Ind Pharm ; 48(7): 333-342, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35983681

RESUMO

OBJECTIVE: The aim was to develop matrix metalloproteinase 1 (MMP1) responsive nanoparticle system for the delivery of 5-fluorouracil (5Fu) anticancer drug. SIGNIFICANCE: The MMP1 in the cancer microenvironment-induced drug release have the advantage of targeted drug release and reduce the distribution of drug to the healthy tissues. METHOD: G5 poly(amidoamine) (PAMAM) dendrimer (G5)-coated gold nanoparticles (G5AuNP) were synthesized and loaded with 5Fu. The drug-loaded nanoparticles were further coated with collagen I (Col-I) peptide, which is a substrate for MMP1 enzyme (Col-I 5Fu@G5AuNP). RESULT: The nanoparticles were highly monodispersed with a particle size of 30 nm and showed high drug encapsulation efficiency. The release of drug from the nanoparticles in HEPES buffer pH 7.4 was faster, higher and better controlled when incubated with MMP1 enzyme. The half-maximum inhibitory concentration for Col-I 5Fu@G5AuNP was eight times lower than the 5Fu against MCF-7, suggesting the improved delivery and anticancer activity of 5Fu after encapsulation in the developed enzyme-responsive nanocarrier system. The computed tomography (CT) X-ray attenuation of Col-I@G5AuNP showed a good contrasting property. CONCLUSION: The formulation Col-I 5Fu@G5AuNP has improved anticancer activity than free drug and the CT imaging results are promising for its theranostic applications for breast cancer treatment.


Assuntos
Antineoplásicos , Dendrímeros , Nanopartículas Metálicas , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Colágeno , Dendrímeros/química , Portadores de Fármacos/química , Fluoruracila/química , Fluoruracila/farmacologia , Ouro/química , HEPES , Metaloproteinase 1 da Matriz , Nanopartículas Metálicas/química , Peptídeos
8.
BMC Genomics ; 21(1): 345, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381023

RESUMO

BACKGROUND: Despite high vaccination coverage using acellular (ACV) and whole-cell pertussis (WCV) vaccines, the resurgence of pertussis is observed globally. Genetic divergence in circulating strains of Bordetella pertussis has been reported as one of the contributing factors for the resurgence of the disease. Our current knowledge of B. pertussis genetic evolution in circulating strains is mostly based on studies conducted in countries using ACVs targeting only a few antigens used in the production of ACVs. To better understand the adaptation to vaccine-induced selection pressure, it will be essential to study B. pertussis populations in developing countries which are using WCVs. India is a significant user and global supplier of WCVs. We report here comparative genome analyses of vaccine and clinical isolates reported from India. Whole-genome sequences obtained from vaccine strains: WCV (J445, J446, J447 and J448), ACV (BP165) were compared with Tohama-I reference strain and recently reported clinical isolates from India (BPD1, BPD2). Core genome-based phylogenetic analysis was also performed using 166 isolates reported from countries using ACV. RESULTS: Whole-genome analysis of vaccine and clinical isolates reported from India revealed high genetic similarity and conserved genome among strains. Phylogenetic analysis showed that clinical and vaccine strains share genetic closeness with reference strain Tohama-I. The allelic profile of vaccine strains (J445:ptxP1/ptxA2/prn1/fim2-1/fim3-1; J446: ptxP2/ptxA4/prn7/fim2-2/fim3-1; J447 and J448: ptxP1/ptxA1/ prn1/fim2-1/fim3-1), which matched entirely with clinical isolates (BPD1:ptxP1/ptxA1/prn1/fim2-1 and BPD2: ptxP1/ptxA1/prn1/fim2-1) reported from India. Multi-locus sequence typing (MLST) demonstrated the presence of dominant sequence types ST2 and primitive ST1 in vaccine strains which will allow better coverage against circulating strains of B. pertussis. CONCLUSIONS: The study provides a detailed characterization of vaccine and clinical strains reported from India, which will further facilitate epidemiological studies on genetic shifts in countries which are using WCVs in their immunization programs.


Assuntos
Bordetella pertussis/genética , Genoma Bacteriano/genética , Vacina contra Coqueluche/genética , Bordetella pertussis/classificação , Bordetella pertussis/imunologia , Bordetella pertussis/isolamento & purificação , Genes Bacterianos/genética , Variação Genética , Genômica , Genótipo , Humanos , Vacina contra Coqueluche/classificação , Filogenia , Coqueluche/microbiologia , Coqueluche/prevenção & controle
9.
Methods ; 158: 33-43, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30690077

RESUMO

We describe here a magnetic bead-based multiplex (pentaplex) immunoassay (MIA) platform developed as an alternative to enzyme-linked immunosorbent assays (ELISA) used in immunogenicity testing of DTaP/TdaP vaccine in animals. MIA simultaneously measures the concentration of serum (IgG) antibodies against B. Pertussis antigens; pertussis toxin, filamentous hemagglutinin (FHA), pertactin (PRN) and tetanus (T) and diphtheria (D) toxoid in the Tdap vaccine immunized animals. Assay validation experiments were done using a panel of serum samples. The results are expressed in IU/ml using WHO reference mice serum. The standard curve was linear with 4PL logistic fit over an eight 2-fold dilution range with LOQ of 0.003, 0.022, 0.005 IU/ml for PT, FHA and PRN and 0.016 U/ml for T and D antigens indicating sensitivity. No interference was observed in monoplex versus multiplex measurements. Specificity was demonstrated by ≥90% homologous and ≤15% heterologous inhibition for all the antigens. The assay was reproducible, with a mean coefficient of variation (CV) of ≤10% for intra-assay duplicates and ≤25% for interassays using different lots of beads and analyst. Accuracy was demonstrated wherein the ratio of observed vs. assigned unitages were within 80-120%. The study suggests that the Pentaplex (MIA) platform meets all the criteria for the serological assay combination vaccines with additional advantages of high throughput, reduced sample volumes, faster analysis with reduced manpower in contrast to conventional monoplex ELISA.


Assuntos
Anticorpos Antibacterianos/isolamento & purificação , Vacinas contra Difteria, Tétano e Coqueluche Acelular/imunologia , Ensaios de Triagem em Larga Escala/métodos , Testes Sorológicos/métodos , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Difteria/sangue , Difteria/imunologia , Difteria/microbiologia , Difteria/prevenção & controle , Ensaio de Imunoadsorção Enzimática/instrumentação , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Ensaios de Triagem em Larga Escala/instrumentação , Humanos , Imunogenicidade da Vacina , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina G/isolamento & purificação , Fenômenos Magnéticos , Masculino , Camundongos , Microesferas , Modelos Animais , Sensibilidade e Especificidade , Testes Sorológicos/instrumentação , Tétano/sangue , Tétano/imunologia , Tétano/microbiologia , Tétano/prevenção & controle , Vacinas Combinadas/imunologia , Coqueluche/sangue , Coqueluche/imunologia , Coqueluche/microbiologia , Coqueluche/prevenção & controle
10.
Dig Dis Sci ; 65(5): 1307-1314, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32162121

RESUMO

Bleeding from the small intestine remains a clinically challenging diagnostic and therapeutic problem. It may be minor, requiring only supplemental iron treatment, to patients who have severe overt bleeding that requires multimodal intervention. This article provides an up-to-date review of the state-of-the-art of diagnosis and treatment of small intestinal bleeding.


Assuntos
Endoscopia por Cápsula/métodos , Hemorragia Gastrointestinal/diagnóstico , Enteropatias/diagnóstico , Melena/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Hemorragia Gastrointestinal/complicações , Humanos , Enteropatias/complicações , Intestino Delgado/diagnóstico por imagem , Masculino , Melena/etiologia , Pessoa de Meia-Idade
11.
FASEB J ; 32(1): 529-534, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28855279

RESUMO

Telomere length (TL) trajectories in somatic tissues during human growth and development are poorly understood. We examined a blood-and-muscle model during early life, focusing on TL trajectories in leukocytes, representing the highly proliferative hematopoietic system, and skeletal muscle, a minimally proliferative tissue. Leukocyte TL (LTL) and skeletal muscle TL (MTL) were measured in 28 fetuses and 73 children. LTL and MTL were highly variable across individuals (sd: fetal LTL = 0.72 kb, MTL = 0.72 kb; children LTL = 0.81 kb, MTL = 0.82 kb) but were highly correlated within individuals (fetuses, r = 0.76, P < 0.0001; children, r = 0.87, P < 0.0001). LTL was shorter than MTL in fetuses (10.63 vs. 11.01 kb; P = 0.0004) and children (8.46 vs. 9.40 kb; <0.0001). The LTL-MTL gap was smaller in fetuses than children. TL in children was inversely correlated with body mass index (BMI) (LTL: -0.047 ± 0.016 kb/BMI, P < 0.005; MTL: -0.037 ± 0.017 kb/BMI, P = 0.03). We conclude that variations in TL across adults and differences in TL between somatic tissues are largely established in early life. Because TL plays a significant role in aging-related diseases, insight into the factors that fashion TL in somatic tissues during early development should contribute to an understanding of the relationship of TL with these disease and longevity in humans.-Sabharwal, S., Verhulst, S., Guirguis, G., Kark, J. D., Labat, C., Roche, N. E., Martimucci, K., Patel, K., Heller, D. S., Kimura, M., Chuang, D., Chuang, A., Benetos, A., Aviv, A. Telomere length dynamics in early life: the blood-and-muscle model.


Assuntos
Modelos Biológicos , Homeostase do Telômero/fisiologia , Feto Abortado/ultraestrutura , Adolescente , Envelhecimento/genética , Envelhecimento/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucócitos/ultraestrutura , Masculino , Músculo Esquelético/ultraestrutura , Homeostase do Telômero/genética , Adulto Jovem
12.
Gastrointest Endosc ; 89(1): 33-43.e4, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29935143

RESUMO

BACKGROUND AND AIMS: Patients presenting with nonhematemesis GI bleeding (NHGIB) represent a diagnostic challenge for physicians. We performed a randomized controlled trial to assess the benefits of deployment of a video capsule soon after admission in the management of patients presenting with melena, hematochezia, or severe anemia compared with standard of care management. METHODS: Patients admitted with NHGIB were randomized and placed into 1 of 2 study groups. In the experimental group, patients ingested a video capsule soon after admission to the hospital. These patients had further endoscopic workup based on the findings from the capsule. Patients in the control group underwent endoscopic evaluation (ie, upper endoscopy, capsule endoscopy, and/or colonoscopy) to identify the source of bleeding as directed by the attending gastroenterologist's interpretation of their clinical presentation. The primary endpoint for this study was the rate of localization of bleeding during hospitalization. RESULTS: Eighty-seven patients were included in this study: 45 randomized to the standard of care arm and 42 to the early capsule arm. A bleeding source was localized in 64.3% of the patients in the early capsule arm and in 31.1% of the patients in the standard of care arm (P < .01). The likelihood of endoscopic localization of bleeding over time was greater for patients receiving early capsule endoscopy compared with those in the standard of care arm (adjusted hazard ratio, 2.77; 95% confidence interval, 1.36-5.64). CONCLUSIONS: For patients admitted to the hospital for NHGIB, early capsule endoscopy is a safe and effective alternative for the detection of the source of bleeding. (Clinical trial registration number: NCT02442830.).


Assuntos
Endoscopia por Cápsula/métodos , Hemorragia Gastrointestinal/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Anemia/etiologia , Colonoscopia/métodos , Diagnóstico Precoce , Endoscopia do Sistema Digestório/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Melena , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Padrão de Cuidado , Fatores de Tempo
13.
Dig Dis Sci ; 64(11): 3040-3047, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31468267

RESUMO

Video capsule endoscopy became a reality in 2001. This device enabled us to directly view the mucosa of the small intestine for the first time. The main indications for the video capsule remain the detection of small intestinal bleeding and iron deficiency anemia, diagnosis and management of Crohn's disease, and detection of tumors. The device is extraordinarily safe and can be used in the very young to the very old. However, there remain several areas of controversy and difficulty. These are covered in this article and include details of indications and contraindications, whether to prepare patients, whether or not to use simethicone and prokinetics. Detection of location of the capsule remains a major engineering challenge. Reading the videos reliably and quickly remains challenging. However, artificial intelligence and machine learning are already on the horizon to provide assistance. New uses for capsule endoscopy promise more accurate diagnosis and hence improved management of acute gastrointestinal bleeding. The colon capsule may eventually help those who refuse conventional colonoscopy, and robotically controlled capsules may be helpful in screening for serious disease in patients with upper abdominal complaints. The advent of the broadening use of video capsule endoscopy is, though it will be controversial, embraced by some and derided by others; such is the nature of technological development. In the long run, if the use of the video capsule, based on sound evidence-based studies, can be shown to improve the care of our patients and reduce the cost of health care, its use will continue to expand.


Assuntos
Endoscopia por Cápsula/normas , Endoscopia Gastrointestinal/normas , Enteropatias/diagnóstico por imagem , Intestino Delgado/diagnóstico por imagem , Endoscopia por Cápsula/métodos , Endoscopia Gastrointestinal/métodos , Humanos , Enteropatias/cirurgia , Intestino Delgado/cirurgia
14.
Acta Neurochir (Wien) ; 161(10): 2013-2026, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31410556

RESUMO

BACKGROUND: In patients with spontaneous subarachnoid haemorrhage (SAH), a vascular cause for the bleed is not always found on initial investigations. This study aimed to systematically evaluate the delayed investigation strategies and clinical outcomes in these cases, often described as "non-aneurysmal" SAH (naSAH). METHODS: A systematic review was performed in concordance with the PRISMA checklist. Pooled proportions of primary outcome measures were estimated using a random-effects model. RESULTS: Fifty-eight studies were included (4473 patients). The cohort was split into perimesencephalic naSAH (PnaSAH) (49.9%), non-PnaSAH (44.7%) and radiologically negative SAH identified on lumbar puncture (5.4%). The commonest initial vascular imaging modality was digital subtraction angiography. A vascular abnormality was identified during delayed investigation in 3.9% [95% CI 1.9-6.6]. There was no uniform strategy for the timing or modality of delayed investigations. The pooled proportion of a favourable modified Rankin scale outcome (0-2) at 3-6 months following diagnosis was 92.0% [95% CI 86.0-96.5]. Complications included re-bleeding (3.1% [95% CI 1.5-5.2]), hydrocephalus (16.0% [95% CI 11.2-21.4]), vasospasm (9.6% [95% CI 6.5-13.3]) and seizure (3.5% [95% CI 1.7-5.8]). Stratified by bleeding pattern, we demonstrate a higher rate of delayed diagnoses (13.6% [95% CI 7.4-21.3]), lower proportion of favourable functional outcome (87.2% [95% CI 80.1-92.9]) and higher risk of complications for non-PnaSAH patients. CONCLUSION: This study highlights the heterogeneity in delayed investigations and outcomes for patients with naSAH, which may be influenced by the initial pattern of bleeding. Further multi-centre prospective studies are required to clarify optimal tailored management strategies for this heterogeneous group of patients.


Assuntos
Angiografia Digital , Hidrocefalia/etiologia , Hemorragia Subaracnóidea/complicações , Feminino , Humanos , Hidrocefalia/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Hemorragia Subaracnóidea/diagnóstico por imagem , Tomografia Computadorizada por Raios X
15.
Eur Spine J ; 27(Suppl 3): 318-322, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-28741148

RESUMO

STUDY DESIGN: Case report. OBJECTIVE: To investigate the feasibility of using two independent image guidance systems to simultaneously fix multiple segment spine fractures. Image guidance is increasingly used to aid spinal fixation. We describe the first use of multiple navigation systems during a single procedure allowing for multi-segment spinal fixations to be performed simultaneously and capitalizing the advantages of navigation. METHOD: Two Medtronic Stealth Station S7™ systems with O-arm image capture were used to guide fixation of C6 and T12, unstable, AO A4, three-column fractures, in a patient with ankylosing spondylitis. RESULTS: Two surgical teams were able to perform cervico-thoracic and thoraco-lumbar fixations simultaneously. Operative time was 2.5 h. Post-operative imaging showed accurate instrumentation placement. The patient recovered without any neurological sequelae. CONCLUSIONS: Optical independence of the Medtronic Stealth Station™ system allowed for simultaneous navigation guided fixation of multiple segment fractures without compromising accuracy. This may result in shortened operative time and morbidity associated with prolonged prone positioning of polytrauma patients, as well as reducing radiation exposure for theatre staff.


Assuntos
Fixação Interna de Fraturas/métodos , Fraturas da Coluna Vertebral/cirurgia , Cirurgia Assistida por Computador/métodos , Vértebras Cervicais/lesões , Vértebras Cervicais/cirurgia , Humanos , Imageamento Tridimensional/métodos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Parafusos Pediculares , Espondilite Anquilosante/complicações , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios X/métodos
17.
World J Microbiol Biotechnol ; 34(10): 150, 2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30255239

RESUMO

This work used an approach of enzyme engineering towards the improved production of baicalin as well as alteration of acceptor and donor substrate preferences in UGT73A16. The 3D model of Withania somnifera family-1 glycosyltransferase (UGT73A16) was constructed based on the known crystal structures of plant UGTs. Structural and functional properties of UGT73A16 were investigated using docking and mutagenesis. The docking studies were performed to understand the key residues involved in substrate recognition. In the molecular model of UGT73A16, substrates binding pockets are located between N- and C-terminal domains. Modeled UGT73A16 was docked with UDP-glucose, UDP-glucuronic acid (UDPGA), kaempferol, isorhamnetin, 3-hydroxy flavones, naringenin, genistein and baicalein. The protein-ligand interactions showed that His 16, Asp 246, Lys 255, Ala 337, Gln 339, Val 340, Asn 358 and Glu 362 amino acid residues may be important for catalytic activity. The kinetic parameters indicated that mutants A337C and Q339A exhibited 2-3 fold and 6-7 fold more catalytic efficiency, respectively than wild type, and shifted the sugar donor specificity from UDP-glucose to UDPGA. The mutant Q379H displayed large loss of activity with UDP-glucose and UDPGA strongly suggested that last amino acid residue of PSPG box is important for glucuronosylation and glucosylation and highly specific to sugar binding sites. The information obtained from docking and mutational studies could be beneficial in future to engineer this biocatalyst for development of better ones.


Assuntos
Glicosiltransferases/química , Glicosiltransferases/metabolismo , Mutagênese , Withania/enzimologia , Sequência de Aminoácidos , Sítios de Ligação , Flavonoides , Cinética , Simulação de Acoplamento Molecular , Mutagênese Sítio-Dirigida , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Conformação Proteica , Alinhamento de Sequência , Análise de Sequência , Homologia de Sequência de Aminoácidos
18.
Nanotechnology ; 28(37): 375501, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28696331

RESUMO

In this article, we report a graphene oxide-based nanosensor incorporating semiconductor quantum dots linked to DNA-aptamers that functions as a 'turn-off' fluorescent nanosensor for detection of low concentrations of analytes. A specific demonstration of this turn-off aptasensor is presented for the case of the detection of mercury (II) ions. In this system, ensembles of aptamer-based quantum-dot sensors are anchored onto graphene oxide (GO) flakes which provide a platform for analyte detection in the vicinity of GO. Herein, the operation of this ensemble-based nanosensor is demonstrated for mercury ions, which upon addition of mercury, quenching of the emission intensity from the quantum dots is observed due to resonance energy transfer between quantum dots and the gold nanoparticle connected via a mercury target aptamer. A key result is that the usually dominant effect of quenching of the quantum dot due to close proximity to the GO can be reduced to negligible levels by using a linker molecule in conjunctions with the aptamer-based nanosensor. The effect of ionic concentration of the background matrix on the emission intensity was also investigated. The sensor system is found to be highly selective towards mercury and exhibits a linear behavior (r 2 > 0.99) in the nanomolar concentration range. The detection limit of the sensor towards mercury with no GO present was found to be 16.5 nM. With GO attached to molecular beacon via 14 base, 35 base, and 51 base long linker DNA, the detection limit was found to be 38.4 nM, 9.45 nM, and 11.38 nM; respectively.

19.
Lung ; 195(4): 403-409, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28456874

RESUMO

BACKGROUND: Systemic sclerosis is a chronic debilitating autoimmune disease characterized by endothelial dysfunction and multi-organ fibrosis. Interstitial lung disease, a common manifestation of SSc, is termed scleroderma-related interstitial lung disease (SSc-ILD) and along with pulmonary hypertension contributes to a majority of deaths in SSc. SSc-ILD patients frequently develop pulmonary hypertension, which prognosticates a poorer outcome. We investigated pulmonary artery dimensions as an outcome predictor in patients with SSc-ILD. METHODS: A retrospective chart review abstracting data from SSc-ILD patients evaluated at a large tertiary care center was performed. HRCT imaging was reviewed and pulmonary artery (PA) and ascending aorta (Ao) diameters were measured for calculation of the PA:Ao ratio. Additionally, demographics, vital signs, spirometric parameters, comorbidities, and mean pulmonary artery pressures were collected when available. Outcome analysis with lung transplant or death events within 4 years based on pulmonary artery size as well as PA:Ao ratio was performed. RESULTS: 70 SSc-ILD patients were identified. Mean pulmonary artery diameter and PA:Ao ratio was 31.17 and 1.07 mm, respectively. Patients with a pulmonary artery diameter ≥32 mm had higher risk of lung transplantation or death (p < 0.001) within 4 years. Patients with a PA:Ao ratio ≥1.1 also had higher risk of lung transplantation or death (p < 0.001) within 4 years. Unadjusted outcomes analyses also identified PA:Ao ratio ≥1.1 as an independent outcome predictor (hazard ratio 3.30, p < 0.001). CONCLUSIONS/CLINICAL IMPLICATIONS: In SSc-ILD patients, a PA:Ao ratio ≥1.1 is associated with higher risk of lung transplant or death. These data suggest that PA:Ao dimension may be used for prognostication in SSc-ILD.


Assuntos
Angiografia por Tomografia Computadorizada , Hipertensão Pulmonar/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Artéria Pulmonar/diagnóstico por imagem , Escleroderma Sistêmico/diagnóstico por imagem , Intervalo Livre de Doença , Feminino , Florida , Humanos , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/terapia , Estimativa de Kaplan-Meier , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/terapia , Transplante de Pulmão , Masculino , Pessoa de Meia-Idade , Ohio , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Escleroderma Sistêmico/mortalidade , Escleroderma Sistêmico/terapia , Fatores de Tempo
20.
Br J Neurosurg ; 30(1): 104-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26313570

RESUMO

The frontobasal approach remains a workhorse for removing large olfactory groove meningiomas. Removal of the orbital bar in addition to standard bifrontal craniotomy allows for additional basal exposure, minimising brain retraction and allowing early and direct access to both the vascular supply and dural origin of this tumour. Here, we describe a simple yet effective modification to the standard orbital bar osteotomy. It has the benefit of being simpler and faster with improved cosmesis compared with an osteotomy of the entire orbital bar. It also has the advantage of not requiring manipulation of the supraorbital nerves or intraorbital or periorbital dissection.


Assuntos
Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Procedimentos Neurocirúrgicos , Órbita/cirurgia , Neoplasias da Base do Crânio/cirurgia , Craniotomia/métodos , Seio Frontal/cirurgia , Humanos , Osteotomia/métodos , Retalhos Cirúrgicos
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