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1.
Medicina (Kaunas) ; 60(5)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38792918

RESUMEN

Training and expertise in regional anaesthesia have increased significantly in tandem with increased interest over the past two decades. This review outlines the most recent advances in regional anaesthesia and focuses on novel areas of interest including fascial plane blocks. Pharmacological advances in the form of the prolongation of drug duration with liposomal bupivacaine are considered. Neuromodulation in the context of regional anaesthesia is outlined as a potential future direction. The growing use of regional anaesthesia outside of the theatre environment and current thinking on managing the rebound plane after regional block regression are also discussed. Recent relevant evidence is summarised, unanswered questions are outlined, and priorities for ongoing investigation are suggested.


Asunto(s)
Anestesia de Conducción , Humanos , Anestesia de Conducción/métodos , Anestesia de Conducción/tendencias , Anestésicos Locales/administración & dosificación , Anestésicos Locales/uso terapéutico , Bloqueo Nervioso/métodos , Bloqueo Nervioso/tendencias , Bupivacaína/administración & dosificación , Bupivacaína/uso terapéutico
2.
Contemp Clin Trials ; 139: 107483, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38431133

RESUMEN

BACKGROUND: Medication non-adherence is common among adolescents and young adults (AYAs) with cancer and associated with poor health outcomes. AYAs with cancer endorse multiple barriers to adherence that differ across individuals, suggesting that tailoring intervention content to an AYA's specific barriers may have the potential to improve adherence. The purpose of this manuscript is to report on ORBIT-guided Phase I design efforts to create the first tailored adherence-promotion intervention for AYAs with cancer and the study protocol for the ongoing Phase II pilot feasibility trial. METHODS: Phase I design included qualitative interviews (n = 15 AYAs) to understand patient preferences for adherence-promotion care, development and refinement of a best-worst scaling exercise barriers tool (n = 5 AYAs), and development of intervention modules and a tailoring algorithm. In the ongoing Phase II pilot feasibility trial, AYAs (ages 15-24 years) with cancer currently taking oral chemotherapy or prophylactic medication will be recruited from three children's hospitals. Feasibility, acceptability, and usability will be assessed and these outcomes along with data on medication adherence will be used to inform the next phases of intervention development and testing. CONCLUSIONS: If promising, this program of research ultimately has the potential to equip clinicians with additional strategies for supporting adherence among AYAs with cancer. NCT05706610.


Asunto(s)
Neoplasias , Adolescente , Humanos , Adulto Joven , Estudios de Factibilidad , Cumplimiento de la Medicación , Neoplasias/tratamiento farmacológico , Proyectos Piloto , Proyectos de Investigación , Ensayos Clínicos Fase II como Asunto
3.
Br J Ophthalmol ; 108(3): 471-475, 2024 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36759150

RESUMEN

AIM: To validate the East London Retinopathy of Prematurity algorithm (EL-ROP) in a cohort of infants at risk of developing retinopathy of prematurity (ROP). METHODS: The EL-ROP algorithm was applied retrospectively to routinely collected data from two tertiary neonatal units in England on infants eligible for ROP screening. The EL-ROP recommendation, to screen or not, was compared with the development of treatment-warranted ROP (TW-ROP) for each infant. The main outcome measures were (1) EL-ROP's sensitivity for predicting the future development of TW-ROP and (2) potential to reduce ROP screening examinations. RESULTS: Data from 568 infants were included in the trial. The median (IQR) birth weight (g) was 875 (704 - 1103) and gestational age (weeks) was 27.0 (25.4 - 29.0). Maternal ethnicity was black (33%) and non-black (67%). 58(10%) developed TW-ROP and in every case this was predicted by the EL-ROP algorithm. It's sensitivity was 100% (95% CI 94-100%) specificity: 44% (95% CI 39-48%) positive predictive value: 17% (95%CI 16-18%), negative predictive value: 100%. CONCLUSIONS: EL-ROP has been validated in a cohort of infants from two tertiary neonatal units in England. Further validation is required before its clinical usefulness can be assessed.


Asunto(s)
Retinopatía de la Prematuridad , Recién Nacido , Lactante , Humanos , Estudios de Cohortes , Retinopatía de la Prematuridad/diagnóstico , Estudios Retrospectivos , Londres/epidemiología , Tamizaje Neonatal , Peso al Nacer , Edad Gestacional , Algoritmos , Factores de Riesgo
4.
PLoS One ; 17(10): e0260907, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36201531

RESUMEN

A genome-wide association study (GWAS) was undertaken to unravel marker-trait associations (MTAs) between SNP markers and phenotypic traits. It involved a subset of 421 cacao accessions from the large and diverse collection conserved ex situ at the International Cocoa Genebank Trinidad. A Mixed Linear Model (MLM) in TASSEL was used for the GWAS and followed by confirmatory analyses using GAPIT FarmCPU. An average linkage disequilibrium (r2) of 0.10 at 5.2 Mb was found across several chromosomes. Seventeen significant (P ≤ 8.17 × 10-5 (-log10 (p) = 4.088)) MTAs of interest, including six that pertained to yield-related traits, were identified using TASSEL MLM. The latter accounted for 5 to 17% of the phenotypic variation expressed. The highly significant association (P ≤ 8.17 × 10-5) between seed length to width ratio and TcSNP 733 on chromosome 5 was verified with FarmCPU (P ≤ 1.12 × 10-8). Fourteen MTAs were common to both the TASSEL and FarmCPU models at P ≤ 0.003. The most significant yield-related MTAs involved seed number and seed length on chromosome 7 (P ≤ 1.15 × 10-14 and P ≤ 6.75 × 10-05, respectively) and seed number on chromosome 1 (P ≤ 2.38 × 10-05), based on the TASSEL MLM. It was noteworthy that seed length, seed length to width ratio and seed number were associated with markers at different loci, indicating their polygenic nature. Approximately 40 candidate genes that encode embryo and seed development, protein synthesis, carbohydrate transport and lipid biosynthesis and transport were identified in the flanking regions of the significantly associated SNPs and in linkage disequilibrium with them. A significant association of fruit surface anthocyanin intensity co-localised with MYB-related protein 308 on chromosome 4. Testing of a genomic selection approach revealed good predictive value (genomic estimated breeding values (GEBV)) for economic traits such as seed number (GEBV = 0.611), seed length (0.6199), seed width (0.5435), seed length to width ratio (0.5503), seed/cotyledon mass (0.6014) and ovule number (0.6325). The findings of this study could facilitate genomic selection and marker-assisted breeding of cacao thereby expediting improvement in the yield potential of cacao planting material.


Asunto(s)
Cacao , Estudio de Asociación del Genoma Completo , Antocianinas , Cacao/genética , Genómica , Genotipo , Desequilibrio de Ligamiento , Lípidos , Fenotipo , Fitomejoramiento , Polimorfismo de Nucleótido Simple
5.
J Am Heart Assoc ; 11(19): e026198, 2022 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-36129031

RESUMEN

Background Methohexital and propofol can both be used as sedation for direct current cardioversion (DCCV). However, there are limited data comparing these medications in this setting. We hypothesized that patients receiving methohexital for elective DCCV would be sedated more quickly, recover from sedation faster, and experience less adverse effects. Methods and Results This was a prospective, blinded randomized controlled trial conducted at a single academic medical center. Eligible participants were randomly assigned to receive either methohexital (0.5 mg/kg) or propofol (0.8 mg/kg) as a bolus for elective DCCV. The times from bolus of the medication to achieving a Ramsay Sedation Scale score of 5 to 6, first shock, eyes opening on command, and when the patient could state their age and name were obtained. The need for additional medication dosing, airway intervention, vital signs, and medication side effects were also recorded. Seventy patients who were randomized to receive methohexital (n=37) or propofol (n=33) were included for analysis. The average doses of methohexital and propofol were 0.51 mg/kg and 0.84 mg/kg, respectively. There were no significant differences between methohexital and propofol in the time from end of injection to loss of conscious (1.4±1.8 versus 1.1±0.5 minutes; P=0.33) or the time to first shock (1.7±1.9 versus 1.4±0.5 minutes; P=0.31). Time intervals were significantly lower for methohexital compared with propofol in the time to eyes opening on command (5.1±2.5 versus 7.8±3.7 minutes; P=0.0005) as well as at the time to the ability to answer simple questions of age and name (6.0±2.6 versus 8.6±4.0 minutes; P=0.001). The methohexital group experienced less hypotension (8.1% versus 42.4%; P<0.001) and less hypoxemia (0.0% versus 15.2%; P=0.005), had lower need for jaw thrust/chin lift (16.2% versus 42.4%; P=0.015), and had less pain on injection compared with propofol using the visual analog scale (7.2±9.7 versus 22.4±28.1; P=0.003). Conclusions In this model of fixed bolus dosing, methohexital was associated with faster recovery, more stable hemodynamics, and less hypoxemia after elective DCCV compared with propofol. It can be considered as a preferred agent for sedation for DCCV. Registration URL: https://www.clinicaltrials.gov/ct; Unique identifier: NCT04187196.


Asunto(s)
Metohexital , Propofol , Cardioversión Eléctrica/efectos adversos , Humanos , Hipoxia , Propofol/efectos adversos , Estudios Prospectivos
6.
Graefes Arch Clin Exp Ophthalmol ; 260(7): 2347-2351, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35122499

RESUMEN

PURPOSE: To describe the evolution of a surgical technique for the correction of large-angle incomitant exodeviations. METHODS: Retrospective review of an interventional case series from 2005 to 2019 in a single centre, with analysis of surgical procedure, prism diopter (PD) deviations and complications. RESULTS: Thirty-one patients underwent surgery at an average age of 42 years (range 4-75 years) for minimal medial rectus function, mostly from oculomotor nerve palsy (23/31; 74%). The mean pre-operative exodeviation was 75 PD (range 30-200PD). Sixteen patients (52%) had undergone previous strabismus surgery. Thirty-eight operations were performed in which the medial rectus insertion was anchored to the periosteum of the posterior lacrimal crest via a retrocaruncular transconjunctival approach. The ipsilateral lateral rectus (LR) was disinserted and fixed to lateral orbital tissue in 29/38 (76%) operations, injected with botulinum toxin in 5, recessed in 2 and had already undergone maximal LR recession in 2. In all but the first 8 operations, temporary limbal sutures were passed through the eyelids to maximally adduct the globe post-operatively. At last follow-up (mean 24 months; range 2-130), the mean reduction in exodeviation was 49PD (range 10-80) and overall residual deviation was 26PD (range 80PD base-in to 14PD base-out). The 5 LR toxin procedures had a mean reduction of 22PD (range 10-40). Seven patients had persistent diplopia, one a transient corneal erosion and one caruncle suture exposure 4 years after surgery. CONCLUSION: Large-angle exodeviations can be markedly improved by bi-rectus fixation. This approach is both safe and effective and can be performed in complex patients with multiple previous procedures.


Asunto(s)
Exotropía , Estrabismo , Adolescente , Adulto , Anciano , Niño , Preescolar , Diplopía , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Músculos Oculomotores/cirugía , Procedimientos Quirúrgicos Oftalmológicos/métodos , Estudios Retrospectivos , Estrabismo/cirugía , Resultado del Tratamiento , Visión Binocular/fisiología , Adulto Joven
7.
Reg Anesth Pain Med ; 47(5): 301-308, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35193970

RESUMEN

BACKGROUND AND OBJECTIVES: Documentation is important for quality improvement, education, and research. There is currently a lack of recommendations regarding key aspects of documentation in regional anesthesia. The aim of this study was to establish recommendations for documentation in regional anesthesia. METHODS: Following the formation of the executive committee and a directed literature review, a long list of potential documentation components was created. A modified Delphi process was then employed to achieve consensus amongst a group of international experts in regional anesthesia. This consisted of 2 rounds of anonymous electronic voting and a final virtual round table discussion with live polling on items not yet excluded or accepted from previous rounds. Progression or exclusion of potential components through the rounds was based on the achievement of strong consensus. Strong consensus was defined as ≥75% agreement and weak consensus as 50%-74% agreement. RESULTS: Seventy-seven collaborators participated in both rounds 1 and 2, while 50 collaborators took part in round 3. In total, experts voted on 83 items and achieved a strong consensus on 51 items, weak consensus on 3 and rejected 29. CONCLUSION: By means of a modified Delphi process, we have established expert consensus on documentation in regional anesthesia.


Asunto(s)
Anestesia de Conducción , Consenso , Técnica Delphi , Documentación , Humanos
8.
Artículo en Inglés | MEDLINE | ID: mdl-35162172

RESUMEN

The aim of this study was to determine the extent to which the Tyme Wear smart shirt is as reliable and valid in detecting personalized ventilatory thresholds when compared to the Parvo Medics TrueOne 2400. In this validation study, 19 subjects were recruited to conduct two graded exercise test (GXT) trials. Each GXT trial was separated by 7 to 10 days of rest. During the GXT, gas exchange and heart rate data were collected by the TrueOne 2400 (TRUE) in addition to the ventilation data collected by the Tyme Wear smart shirt (S-PRED). Gas exchange data from TRUE were used to detect ventilatory threshold 1 (VT1) and ventilatory threshold 2 (VT2). TRUE and S-PRED VT1 and VT2 were compared to determine the reliability and validity of the smart shirt. Of the 19 subjects, data from 15 subjects were used during analysis. S-PRED exhibited excellent (intraclass correlation coefficient-CC > 0.90) reliability for detection of VT1 and VT2 utilizing time point and workload and moderate (0.90 > ICC > 0.75) reliability utilizing heart rate. TRUE exhibited excellent reliability for detection of VT1 and VT2 utilizing time point, workload, and heart rate. When compared to TRUE, S-PRED appears to underestimate the VT1 workload (p > 0.05) across both trials and heart rate (p < 0.05) for trial 1. However, S-PRED appears to underestimate VT2 workload (p < 0.05) and heart rate (p < 0.05) across both trials. The result from this study suggests that the Tyme Wear smart shirt is less valid but is comparable in reliability when compared to the gold standard. Moreover, despite the underestimation of S-PRED VT1 and VT2, the S-PRED-detected personalized ventilatory thresholds provide an adequate training workload for most individuals. In conclusion, the Tyme Wear smart shirt provides easily accessible testing to establish threshold-guided training zones but does not devalue the long-standing laboratory equivalent.


Asunto(s)
Umbral Anaerobio , Consumo de Oxígeno , Umbral Anaerobio/fisiología , Prueba de Esfuerzo , Frecuencia Cardíaca/fisiología , Humanos , Consumo de Oxígeno/fisiología , Ventilación Pulmonar , Reproducibilidad de los Resultados
10.
J Bacteriol ; 203(7)2021 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-33468596

RESUMEN

Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes that assist in protein folding around proline-peptide bonds, and they often possess chaperone activity. Staphylococcus aureus encodes three PPIases, i.e., PrsA, PpiB, and trigger factor (TF). Previous work by our group demonstrated a role for both PrsA and PpiB in S. aureus; however, TF remains largely unstudied. Here, we identify a role for TF in S. aureus biofilm formation and demonstrate cooperation between TF and the cytoplasmic PPIase PpiB. Mutation of the tig gene (encoding TF) led to reduced biofilm development in vitro but no significant attenuation of virulence in a mouse model of infection. To investigate whether TF possesses chaperone activity, we analyzed the ability of a tig mutant to survive acid and base stress. While there was no significant decrease for a tig mutant, a ppiBtig double mutant exhibited significant decreases in cell viability after acid and base challenges. We then demonstrated that a ppiB tig double mutant had exacerbated phenotypes in vitro and in vivo, compared to either single mutant. Finally, in vivo immunoprecipitation of epitope-tagged PpiB revealed that PpiB interacted with 4 times the number of proteins when TF was absent from the cell, suggesting that it may be compensating for the loss of TF. Interestingly, the only proteins found to interact with TF were TF itself, fibronectin-binding protein B (FnBPB), and the chaperone protein ClpB. Collectively, these results support the first phenotype for S. aureus TF and demonstrate a greater network of cooperation between chaperone proteins in Staphylococcus aureusIMPORTANCES. aureus encodes a large number of virulence factors that aid the bacterium in survival and pathogenesis. These virulence factors have a wide variety of functions; however, they must all be properly secreted in order to be functional. Bacterial chaperone proteins often assist in secretion by trafficking proteins to secretion machinery or assisting in proper protein folding. Here, we report that the S. aureus chaperone TF contributes to biofilm formation and cooperates with the chaperone PpiB to regulate S. aureus virulence processes. These data highlight the first known role for TF in S. aureus and suggest that S. aureus chaperone proteins may be involved in a greater regulatory network in the cell.


Asunto(s)
Biopelículas/crecimiento & desarrollo , Regulación Bacteriana de la Expresión Génica/fisiología , Isomerasa de Peptidilprolil/metabolismo , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/metabolismo , Secuencia de Aminoácidos , Animales , Proteínas Bacterianas , Sangre/microbiología , Sistema Libre de Células , Regulación Enzimológica de la Expresión Génica , Hemólisis , Humanos , Ratones , Chaperonas Moleculares , Isomerasa de Peptidilprolil/genética , Staphylococcus aureus/genética , Staphylococcus aureus/fisiología
12.
Ophthalmol Glaucoma ; 4(2): 139-148, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32931948

RESUMEN

PURPOSE: To explore the demographic and clinical variables associated with intraocular pressure (IOP) lowering after cataract extraction (CE) alone or CE in combination with the iStent (Glaukos Corporation) placement (CE+IS). DESIGN: Retrospective data extraction and survival analysis of consecutive patients identified over a 2-year period. PARTICIPANTS: Patients with mild to moderate glaucoma who underwent CE (48 eyes of 32 patients) or CE+IS (61 eyes of 37 patients) were analyzed. METHODS: Inability to reduce the number of medications or the IOP by at least 20% compared with baseline on 2 consecutive visits was considered surgical failure. Using Cox proportional hazards models, survival analysis was performed, and demographic and clinical variables were evaluated as risk factors. MAIN OUTCOME MEASURES: Time to failure after surgical procedure. RESULTS: CE+IS had lower odds of failure than CE alone (hazard ratio [HR], 2.01; P = 0.047). In White patients, CE+IS showed greater odds of success compared with CE alone (HR, 2.86; P = 0.007). For non-White patients, no difference was found in the outcomes for the 2 procedures (HR, 0.59; P = 0.48). In the multivariate analysis, non-White race (HR, 8.75; P = 0.0002) and longer axial length (HR, 1.61; P = 0.03) were associated with greater hazard of failure after CE+IS. In the CE group, greater odds of failure were associated with steeper corneal curvature (HR, 1.74; P = 0.008), shallower anterior chamber (HR, 0.22; P = 0.008), and longer axial length (HR, 1.58; P = 0.01). CONCLUSIONS: Addition of the iStent to CE improved the duration of IOP lowering in White patients, but not in non-White patients. Associations between IOP lowering after CE and biometric parameters may allow for leveraging these clinical parameters for better case selection for these procedures.


Asunto(s)
Extracción de Catarata , Implantes de Drenaje de Glaucoma , Glaucoma de Ángulo Abierto , Facoemulsificación , Glaucoma de Ángulo Abierto/cirugía , Humanos , Presión Intraocular , Facoemulsificación/efectos adversos , Estudios Retrospectivos
13.
Am J Community Psychol ; 66(3-4): 222-231, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32578886

RESUMEN

Childhood asthma disparities persist, with children living in low-income areas experiencing worse morbidity. We partnered with a community-academic research team and stakeholders to conduct a needs assessment to understand barriers and supports to asthma treatment. We convened a community advisory board, comprised of parents of children with asthma, youth with asthma, and members of key community organizations. Two focus groups with parents of children with asthma and four focus groups with youth with asthma were conducted, and a survey was administered to 100 parents. A visual mapping process was used to gather qualitative data about barriers, strategies, and outcomes, and allowed advisory board members to interpret focus group and survey data within the lived experiences of families. Focus group themes included parent stress/anxiety, concerns about school nurses, and lack of trust in providers. Findings from focus groups and surveys suggested that emergency department visits were not perceived negatively by families, although health providers and researchers generally view them as such. Public health implications include systemic changes that allow the healthcare system to address families' acute needs and worry. A community program focused on education and coordination among families, schools, and medical homes might improve asthma outcomes at the population level.


Asunto(s)
Asma/terapia , Disparidades en el Estado de Salud , Evaluación de Necesidades , Adolescente , Adulto , Anciano , Niño , Preescolar , Servicios de Salud Comunitaria , Femenino , Grupos Focales , Humanos , Masculino , Persona de Mediana Edad , Padres , Investigación Cualitativa , Instituciones Académicas , Encuestas y Cuestionarios , Adulto Joven
14.
Eur J Pediatr ; 179(10): 1603-1607, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32367329

RESUMEN

The aim of this study is to evaluate current anaesthetic practice for retinopathy of prematurity (ROP) interventions in the UK. We collected the data from the 12-month prospective British Ophthalmic Surveillance Unit study carried out in 2013/2014 that were analysed with regard to type of anaesthesia used for primary ROP procedures and the hospital department in which treatment took place. A total of 327 cases of treated ROP from 55 different UK units were reported in the study. Type of anaesthesia used during treatment was available for 324 (99.1%) cases and the treatment location in 316 (96.6%). Overall, 266 (89.3%) laser treatments and 13 (50.0%) of primary intravitreal injections were performed with the neonate intubated, using intravenous sedation (IVS) in 158 (59.4%) and the remainder, under general anaesthesia (GA). Two hundred thirteen (67.4%) of all ROP procedures took place in the neonatal unit. GA was used in 98 (95.1%) of theatre cases compared with 19 (8.9%) of cases treated in the neonatal unit. Three (0.9%) neonates suffered significant respiratory distress during or immediately after laser treatment.Conclusion: This survey suggests that the preference in UK units is to undertake ROP laser treatment in the neonatal unit with the neonate intubated and sedated intravenously. Those babies treated in the operating theatre are more likely to receive GA. In the surveyed year, half of the neonates receiving intravitreal injections as sole primary therapy was intubated; the reason for this could not be elucidated from the responses. Adverse respiratory reactions during or after laser treatment affected fewer than 1% of the neonates in this study. What is Known: • Prior to the introduction of intravitreal anti-VEGF, almost all ROP treatments in the UK were performed under general anaesthetic (GA). • The technique of intravitreal injection is described using topical anaesthesia and was thought to be changing anaesthesia preferences for ROP treatment. What is New: • Half of the neonates receiving primary anti-VEGF injection in the UK were treated under intravenous sedation or GA. • The increasing use of primary anti-VEGF treatment has not influenced trends in anaesthetic practice in the UK since the last review 10 years ago.


Asunto(s)
Anestésicos , Retinopatía de la Prematuridad , Anestesia Local , Edad Gestacional , Humanos , Lactante , Recién Nacido , Estudios Prospectivos , Retinopatía de la Prematuridad/epidemiología , Retinopatía de la Prematuridad/terapia , Reino Unido/epidemiología
15.
Toxins (Basel) ; 11(6)2019 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-31208155

RESUMEN

Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes that catalyze the cis-to-trans isomerization around proline bonds, allowing proteins to fold into their correct confirmation. Previously, we identified two PPIase enzymes in Staphylococcus aureus (PpiB and PrsA) that are involved in the regulation of virulence determinants and have shown that PpiB contributes to S. aureus virulence in a murine abscess model of infection. Here, we further examine the role of these PPIases in S. aureus virulence and, in particular, their regulation of hemolytic toxins. Using murine abscess and systemic models of infection, we show that a ppiB mutant in a USA300 background is attenuated for virulence but that a prsA mutant is not. Deletion of the ppiB gene leads to decreased bacterial survival in macrophages and nasal epithelial cells, while there is no significant difference when prsA is deleted. Analysis of culture supernatants reveals that a ppiB mutant strain has reduced levels of the phenol-soluble modulins and that both ppiB and prsA mutants have reduced alpha-toxin activity. Finally, we perform immunoprecipitation to identify cellular targets of PpiB and PrsA. Results suggest a novel role for PpiB in S. aureus protein secretion. Collectively, our results demonstrate that PpiB and PrsA influence S. aureus toxins via distinct mechanisms, and that PpiB but not PrsA contributes to disease.


Asunto(s)
Proteínas Bacterianas/metabolismo , Toxinas Bacterianas/metabolismo , Isomerasa de Peptidilprolil/metabolismo , Infecciones Estafilocócicas/metabolismo , Staphylococcus aureus/patogenicidad , Factores de Virulencia/metabolismo , Animales , Células Epiteliales/microbiología , Eritrocitos/efectos de los fármacos , Femenino , Hemólisis/efectos de los fármacos , Humanos , Macrófagos/microbiología , Ratones Endogámicos BALB C , Conejos , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/metabolismo , Células THP-1 , Virulencia
16.
Am J Surg ; 218(2): 315-322, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30954232

RESUMEN

INTRODUCTION: We report the results of a multicenter trial evaluating a unique, biological mesh (MIROMESH) derived from decellularized porcine liver for hiatal cruralplasty during laparoscopic PEHR. METHODS: 41 subjects underwent a laparoscopic PEHR which included primary crural closure, and MIROMESH onlay. Subjects were assessed at 2-weeks and 6, 12, 18 and 24 months using the SF-36, GERD-HRQL questionnaire, and VAS GERD related symptoms, and UGI. RESULTS: Mean procedure time was 143.0 (±45.2) minutes, 93% had a Type III hiatal hernia and median LOS was 3 days. Of 27 patients available for 2 years follow up, no patients required surgical reintervention for symptomatic hernia recurrence or adverse events. Radiographic follow up revealed a 10% hiatal hernia recurrence rate. GERD HRQL scores were significantly improved from baseline to two years follow up. All the GERD symptoms measured showed significant and sustained improvement at all post-operative time periods. CONCLUSION: The utilization of MIROMESH for crural reinforcement during laparoscopic PEHR resulted in excellent symptomatic improvement in our multicenter trial with a 10% 2 year radiographic recurrence rate.


Asunto(s)
Bioprótesis , Hernia Hiatal/cirugía , Herniorrafia/métodos , Laparoscopía , Mallas Quirúrgicas , Adulto , Anciano , Animales , Femenino , Humanos , Hígado , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diseño de Prótesis , Porcinos
17.
J Pediatr Ophthalmol Strabismus ; 56(1): 43-49, 2019 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-30371912

RESUMEN

PURPOSE: To report the surgical outcomes of children with cataract associated with microphthalmia, microcornea, or persistent fetal vasculature (MMP) and children with isolated cataract. METHODS: The study included 111 children (cataract associated with MMP: n = 25) who underwent cataract surgery at younger than 16 years. Exclusion criteria were duration of follow-up less than 5 years, intraindividual differences in age at surgery, eye disorders other than MMP, secondary cataract, and syndromal diseases. Main outcome measures were proportion of eyes with glaucoma and best corrected visual acuity (BCVA). Both groups were dichotomized by age at surgery (early intervention group: ≤ 48 days). Descriptive analysis was performed throughout. RESULTS: Median age at surgery was 3.9 months for cataract associated with MMP and 23.3 months for isolated cataract. The median (interquartile range [IQR]) duration of follow-up was 95.9 months (range: 76.0 to 154.5 months). In children with bilateral cataract associated with MMP, the proportion of eyes with final BCVA worse than 0.3 logMAR was similar regardless of age at surgery (early intervention: 80%, later intervention: 78%). In bilateral isolated cataract, the proportions were 56% and 33%, respectively. Children with cataract associated with MMP had a high prevalence of glaucoma (28%). Glaucoma prevalence was lower in the later intervention group. CONCLUSIONS: In the presence of MMP, early cataract surgery is associated with a high risk of post-lensectomy glaucoma, but does not offer the benefit of better visual outcomes. [J Pediatr Ophthalmol Strabismus. 2019;56(1):43-49.].


Asunto(s)
Enfermedades de la Córnea/cirugía , Manejo de la Enfermedad , Microftalmía/cirugía , Procedimientos Quirúrgicos Oftalmológicos/métodos , Síndrome de Circulación Fetal Persistente/cirugía , Catarata/diagnóstico , Niño , Preescolar , Enfermedades de la Córnea/diagnóstico , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Microftalmía/diagnóstico , Estudios Retrospectivos , Factores de Tiempo
18.
PLoS One ; 13(6): e0199074, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29902283

RESUMEN

BACKGROUND: Botulinum toxin injection chemodenervation is a well-established intervention for adult strabismus, and has also been recognised as an effective alternative to routine incisional surgery for paediatric disease. We aimed to investigate the temporal patterns of practice, indications and outcomes of chemodenervation for paediatric strabismus at national and tertiary centre level. METHODS: Retrospective study using routinely collected patient data: Hospital Episode Statistics (HES) data were used to identify children undergoing non-incisional strabismus procedures in England from 2007 to 2016. Single-centre retrospective data on children undergoing botulinum toxin injections (Dysport® 2.5 units/ 0.1ml) as an isolated intervention (not involving incisional procedures) was undertaken to identify indications and outcomes. Successful outcome was defined as deviation <11 prism dioptres (PD). RESULTS: Between 2007 and 2016, there was no increase in the proportion of childhood strabismus involving non-incisional procedures. Amongst 150 children undergoing chemodenervation for strabismus within the tertiary centre, the most common diagnoses were acute onset esotropia (n = 34), infantile esotropia (n = 16) and consecutive exotropia (n = 15). Median age at injection was 8.5 years (range 0.9-15 years), and median follow up 12 months (6 months-11 years). Success rates differed by diagnosis, from 66% (non or partially accommodative esotropia) to 0% (congenital cranial disorders). Adverse events were seen in 62/150, 41%, most commonly transient ptosis (39%, n = 58). Overcorrection was seen in 14/119, 13%. Mild subconjunctival haemorrhage (n = 2) was the only other adverse event. CONCLUSIONS: Botulinum toxin for childhood strabismus has an acceptable safety profile, and considerable potential therapeutic benefit. However, nationally there has been no increased uptake of chemodenervation non-incisional procedures. Further prospective studies are necessary to understand the predictors of outcome within the separate clinical subgroups, to guide clinical decision making.


Asunto(s)
Toxinas Botulínicas/farmacología , Bloqueo Nervioso , Estrabismo/tratamiento farmacológico , Toxinas Botulínicas/efectos adversos , Toxinas Botulínicas/uso terapéutico , Niño , Inglaterra , Humanos , Bloqueo Nervioso/efectos adversos , Estudios Retrospectivos , Seguridad , Resultado del Tratamiento
19.
J Magn Reson Imaging ; 48(2): 431-440, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29357200

RESUMEN

BACKGROUND: There is growing interest in detecting cerebro-cerebellar circuits, which requires adequate blood oxygenation level dependent contrast and signal-to-noise ratio (SNR) throughout the brain. Although 7T scanners offer increased SNR, coverage of commercial head coils is currently limited to the cerebrum. PURPOSE: To improve cerebellar functional MRI (fMRI) at 7T with high permittivity material (HPM) pads extending the sensitivity of a commercial coil. STUDY TYPE: Simulations were used to determine HPM pad configuration and assess radiofrequency (RF) safety. In vivo experiments were performed to evaluate RF field distributions and SNR and assess improvements of cerebellar fMRI. SUBJECTS: Eight healthy volunteers enrolled in a prospective motor fMRI study with and without HPM. FIELD STRENGTH/SEQUENCE: Gradient echo (GRE) echo planar imaging for fMRI, turbo FLASH for flip angle mapping, GRE sequence for SNR maps, and T1 -weighted MPRAGE were acquired with and without HPM pads at 7T. ASSESSMENT: Field maps, SNR maps, and anatomical images were evaluated for coverage. Simulation results were used to assess SAR levels of the experiment. Activation data from fMRI experiments were compared with and without HPM pads. STATISTICAL TESTS: fMRI data were analyzed using FEAT FSL for each subject followed by group level analysis using paired t-test of acquisitions with and without HPM. RESULTS: Simulations showed 52% improvement in transmit efficiency in cerebellum with HPM and SAR levels well below recommended limits. Experiments showed 27% improvement in SNR in cerebellum and improvement in coverage on T1 -weighted images. fMRI showed greater cerebellar activation in individual subjects with the HPM pad present (Z > = 4), especially in inferior slices of cerebellum, with 59% average increase in number of activated voxels in the cerebellum. Group-level analysis showed improved functional activation (Z > = 2.3) in cerebellar regions with HPM pads without loss of measured activation elsewhere. DATA CONCLUSION: HPM pads can improve cerebellar fMRI at 7T with a commonly-used head coil without compromising RF safety. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2018;48:431-440.


Asunto(s)
Encéfalo/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/instrumentación , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética , Adulto , Simulación por Computador , Medios de Contraste/química , Diseño de Equipo , Femenino , Humanos , Aumento de la Imagen/métodos , Masculino , Fantasmas de Imagen , Estudios Prospectivos , Ondas de Radio , Reproducibilidad de los Resultados , Relación Señal-Ruido
20.
Magn Reson Med ; 80(1): 391-399, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29193307

RESUMEN

PURPOSE: The aim of this study was to evaluate the effect of integrated high-permittivity materials (HPMs) on excitation homogeneity and global specific absorption rate (SAR) for transmit arrays at 7T. METHODS: A rapid electrodynamic simulation framework was used to calculate L-curves associated with excitation of a uniform 2D profile in a dielectric sphere. We used ultimate intrinsic SAR as an absolute performance reference to compare different transmit arrays in the presence and absence of a layer of HPM. We investigated the optimal permittivity for the HPM as a function of its thickness, the sample size, and the number of array elements. RESULTS: Adding a layer of HPM can improve the performance of a 24-element array to match that of a 48-element array without HPM, whereas a 48-element array with HPM can perform as well as a 64-element array without HPM. Optimal relative permittivity values changed based on sample and coil geometry, but were always within a range obtainable with readily available materials (εr = 100-200). CONCLUSION: Integration of HPMs could be a practical method to improve RF shimming performance, alternative to increasing the number of coils. The proposed simulation framework could be used to explore the design of novel transmit arrays for head imaging at ultra-high field strength. Magn Reson Med 80:391-399, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Asunto(s)
Aumento de la Imagen/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/instrumentación , Ondas de Radio , Algoritmos , Simulación por Computador , Diseño de Equipo , Cabeza/diagnóstico por imagen , Humanos , Campos Magnéticos , Imagen por Resonancia Magnética/métodos , Fantasmas de Imagen
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