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1.
N Z Vet J ; : 1-15, 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38910032

RESUMEN

Horses are exquisitely sensitive to tetanus neurotoxin and are exposed to the risk of infection with Clostridium tetani throughout life. The vaccine against tetanus is highly effective at preventing disease, whereas tetanus in unvaccinated populations is associated with high mortality rates. Current guidelines in New Zealand and Australia for the available vaccine contain contradictions and limitations surrounding the optimal tetanus immunisation protocols for both adult horses and foals. This review critically evaluates the scientific literature on tetanus prophylaxis in horses within the context of equine practice and available products in New Zealand and Australia. The review was conducted by a panel of industry and specialist veterinarians to obtain agreement on nine equine tetanus prophylaxis guidelines for practising veterinarians. The primary protocol for tetanus toxoid (TT) immunisation consists of a three-dose series IM for all horses ≥ 6 months of age, and a four-dose series IM is proposed if commencing vaccination in foals between 3 and 6 months of age. Tetanus prophylaxis in foals < 3 months of age relies on passive immunity strategies. Following the completion of the primary protocol, a TT booster dose IM should be administered within 5 years, and every 5 years thereafter. When followed, these protocols should provide adequate protection against tetanus in horses. Additional tetanus prophylaxis guidelines are provided for veterinarians attending a horse experiencing a known "risk event" (e.g. wound, hoof abscess, surgery, umbilical infection). When a correctly vaccinated horse experiences a risk event, pre-existing immunity provides protection against tetanus. When an unvaccinated horse or one with unknown vaccination status, or a foal born to an unvaccinated dam, experiences a risk event, TT IM and tetanus antitoxin (TAT) 1,500 IU SC should be administered simultaneously at separate sites, and the TT primary immunisation protocol should subsequently be completed for the horse's respective age. In previously immunised pregnant broodmares, a TT booster dose administered 4-8 weeks prior to parturition optimises the transfer of passive immunity against tetanus to the newborn foal via colostrum; provided that post-natal IgG concentration in serum is > 800 mg/dL (8 g/L), such foals should be passively protected against tetanus up to 6 months of age. Survivors of clinical tetanus must still receive the primary protocol for vaccination against tetanus. In summary, all horses in New Zealand and Australia should be vaccinated against tetanus with protection maintained throughout life via TT booster doses, facilitated by accurate medical record keeping and client education.

2.
Phys Rev Lett ; 128(2): 023601, 2022 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-35089759

RESUMEN

The ability to manipulate and measure the time-frequency structure of quantum light is useful for information processing and metrology. Measuring this structure is also important when developing quantum light sources with high modal purity that can interfere with other independent sources. Here, we present and experimentally demonstrate a scheme based on intensity interferometry to measure the joint spectral mode of photon pairs produced by spontaneous parametric down-conversion. We observe correlations in the spectral phase of the photons due to chirp in the pump. We show that our scheme can be combined with stimulated emission tomography to quickly measure their mode using bright classical light. Our scheme does not require phase stability, nonlinearities, or spectral shaping and thus is an experimentally simple way of measuring the modal structure of quantum light.

3.
Opt Lett ; 46(11): 2565-2568, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-34061057

RESUMEN

The discrimination of coherent states is a key task in optical communication and quantum key distribution protocols. In this work, we use a photon-number-resolving detector, the transition-edge sensor, to discriminate binary-phase-shifted coherent states at a telecom wavelength. Owing to its dynamic range and high efficiency, we achieve a bit error probability that unconditionally exceeds the standard quantum limit (SQL) by up to 7.7 dB. The improvement to the SQL persists for signals containing up to approximately seven photons on average and is achieved in a single shot (i.e., without measurement feedback), thus making our approach compatible with larger bandwidths.

4.
J Eur Acad Dermatol Venereol ; 34(10): 2402-2408, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32236987

RESUMEN

BACKGROUND: Data regarding the course and treatment of pigmented purpuric dermatoses (PPD) in the paediatric population are limited. Although treatments for pigmented purpura are not well established, vitamin C and rutoside have been reported to be an effective treatment option and are widely utilized. OBJECTIVE: To assess the clinical course and utility of vitamin C and rutoside in paediatric patients with PPD treated at Ann & Robert H. Lurie Children's Hospital of Chicago between 2008 and 2018. METHODS: A retrospective review of all children with PPD managed at our hospital between 2008 and 2018 was performed. Additional follow-up was obtained via telephone interviews. RESULTS: A total of 101 patients met inclusion criteria. The female: male ratio was 1.3 : 1, and the median age at diagnosis was 8.8 years (IQR, 5.7-12.9). Median follow-up was 7.13 months (IQR, 3-17.4). The most common PPD subtypes were lichen aureus (43%) and Schamberg (34%). Fifty-three (52%) patients had evaluable follow-up documentation via their medical record or phone questionnaire. Twenty-eight patients were treated with vitamin C or rutoside or combination therapy. Twenty-five patients received no treatment. Clearance of the rash was noted in 24 (45.3%) patients overall, including 10 (42%) patients in the treated group and 14 (58%) patients in the untreated group. Recurrence was noted in seven (13.2%) patients. Treatment with vitamin C and/or rutoside was well tolerated without side effects. None of the patients were subsequently diagnosed with vasculitis, coagulopathy or cutaneous T-cell lymphoma. CONCLUSION: Pigmented purpuric dermatosis in children is a benign disorder with high rates of complete resolution. Treatment with vitamin C and rutoside is well tolerated, but in this cohort, there did not appear to be an advantage over watchful waiting without therapy.


Asunto(s)
Púrpura , Neoplasias Cutáneas , Niño , Femenino , Humanos , Masculino , Recurrencia Local de Neoplasia , Púrpura/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento
5.
BMC Med ; 17(1): 232, 2019 12 30.
Artículo en Inglés | MEDLINE | ID: mdl-31888667

RESUMEN

BACKGROUND: Repeated outbreaks of emerging pathogens underscore the need for preparedness plans to prevent, detect, and respond. As countries develop and improve National Action Plans for Health Security, addressing subnational variation in preparedness is increasingly important. One facet of preparedness and mitigating disease transmission is health facility accessibility, linking infected persons with health systems and vice versa. Where potential patients can access care, local facilities must ensure they can appropriately diagnose, treat, and contain disease spread to prevent secondary transmission; where patients cannot readily access facilities, alternate plans must be developed. Here, we use travel time to link facilities and populations at risk of viral hemorrhagic fevers (VHFs) and identify spatial variation in these respective preparedness demands. METHODS AND FINDINGS: We used geospatial resources of travel friction, pathogen environmental suitability, and health facilities to determine facility accessibility of any at-risk location within a country. We considered in-country and cross-border movements of exposed populations and highlighted vulnerable populations where current facilities are inaccessible and new infrastructure would reduce travel times. We developed profiles for 43 African countries. Resulting maps demonstrate gaps in health facility accessibility and highlight facilities closest to areas at risk for VHF spillover. For instance, in the Central African Republic, we identified travel times of over 24 h to access a health facility. Some countries had more uniformly short travel times, such as Nigeria, although regional disparities exist. For some populations, including many in Botswana, access to areas at risk for VHF nationally was low but proximity to suitable spillover areas in bordering countries was high. Additional analyses provide insights for considering future resource allocation. We provide a contemporary use case for these analyses for the ongoing Ebola outbreak. CONCLUSIONS: These maps demonstrate the use of geospatial analytics for subnational preparedness, identifying facilities close to at-risk populations for prioritizing readiness to detect, treat, and respond to cases and highlighting where gaps in health facility accessibility exist. We identified cross-border threats for VHF exposure and demonstrate an opportunity to improve preparedness activities through the use of precision public health methods and data-driven insights for resource allocation as part of a country's preparedness plans.


Asunto(s)
Defensa Civil/métodos , Brotes de Enfermedades/prevención & control , Instituciones de Salud/normas , Viaje/tendencias , Humanos , Factores de Tiempo
6.
Proc Biol Sci ; 285(1887)2018 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-30257911

RESUMEN

In birds, vocal learning enables the production of sexually selected complex songs, dialects and song copy matching. But stressful conditions during development have been shown to affect song production and complexity, mediated by changes in neural development. However, to date, no studies have tested whether early-life stress affects the neural processes underlying vocal learning, in contrast to song production. Here, we hypothesized that developmental stress alters auditory memory formation and neural processing of song stimuli. We experimentally stressed male nestling zebra finches and, in two separate experiments, tested their neural responses to song playbacks as adults, using either immediate early gene (IEG) expression or electrophysiological response. Once adult, nutritionally stressed males exhibited a reduced response to tutor song playback, as demonstrated by reduced expressions of two IEGs (Arc and ZENK) and reduced neuronal response, in both the caudomedial nidopallium (NCM) and mesopallium (CMM). Furthermore, nutritionally stressed males also showed impaired neuronal memory for novel songs heard in adulthood. These findings demonstrate, for the first time, that developmental conditions affect auditory memories that subserve vocal learning. Although the fitness consequences of such memory impairments remain to be determined, this study highlights the lasting impact early-life experiences can have on cognitive abilities.


Asunto(s)
Encéfalo/fisiología , Pinzones/fisiología , Memoria/fisiología , Vocalización Animal/fisiología , Estimulación Acústica , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Encéfalo/metabolismo , Cognición , Femenino , Pinzones/crecimiento & desarrollo , Perfilación de la Expresión Génica , Genes Inmediatos-Precoces , Masculino , Estrés Fisiológico
7.
Opt Express ; 26(13): 17145-17157, 2018 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-30119530

RESUMEN

In this work, we investigate the properties of four-wave mixing Bragg scattering driven by orthogonally polarized pumps in a birefringent waveguide. This configuration enables a large signal conversion bandwidth, and allows strongly unidirectional frequency conversion as undesired Bragg-scattering processes are suppressed by waveguide birefringence. Moreover, we show that this form of Bragg scattering preserves the (arbitrary) signal pulse shape, even when driven by pulsed pumps.

8.
Vox Sang ; 113(1): 13-20, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28952159

RESUMEN

BACKGROUND AND OBJECTIVES: Australia introduced bacterial contamination screening (BCS) for platelet components in April 2008. This study presents analysis performed to assess the efficacy of testing. MATERIALS AND METHODS: Seven-day aerobic and anaerobic culture is performed using the BacT/ALERT 3D system. Following an initial machine positive (IMP) flag, all associated components are recalled, and/or clinicians treating already transfused patients are notified. IMPs are categorized as 'machine false positive', 'confirmed positive' or 'indeterminate' depending on culture results of initial and repeat samples. RESULTS: Between 2010 and 2012, 1·1% of platelet donations tested IMP; since 2013, this rate has fallen to 0·6% through improved instrument management, reducing false-positive IMPs but maintaining sensitivity for cultures yielding bacterial growth. On average, 66% of confirmed positive and indeterminate platelet units had been transfused at the time of detection. The majority (95%) of these grew Propionibacterium sp., a slow-growing organism that rarely causes sepsis in the transfusion setting. The incidence of reported transfuion-transmitted bacterial infection (TTBI) has fallen since the introduction of BCS, with a 4·2-fold [0·5, 28·2] lower rate from platelets. CONCLUSION: BCS has been successful in detecting platelet units containing pathogenic bacteria. The incidence of TTBI from platelets has fallen since the introduction of BCS, but the risk has not been eliminated due to rare false-negative results. In the absence of a pathogen inactivation system for red blood cells, BCS provides 'surrogate' testing of red blood cells from which platelets have been manufactured.


Asunto(s)
Infecciones Bacterianas/prevención & control , Plaquetas/microbiología , Australia/epidemiología , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/transmisión , Seguridad de la Sangre , Técnicas de Cultivo , Humanos , Incidencia , Transfusión de Plaquetas/efectos adversos
9.
Opt Express ; 25(21): 26067-26075, 2017 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-29041268

RESUMEN

Generating N single photons simultaneously is a formidable challenge due to the lack of deterministic single photon sources. Recent work [New J. Phys. 19, 063013 (2017] has proposed a relative multiplexing scheme that can enhance the N single photons probability with a minimum of active switching resources. We experimentally demonstrate relative temporal multiplexing on two photon sources with a 90% additional enhancement over the standard temporal multiplexing scheme demonstrated previously. 88 ± 11% visibility of Hong-Ou-Mandel quantum interference verifies the indistinguishability of the heralded single photons after the synchronization. This proof-of-principle demonstration points out the potential significance of the relative multiplexing scheme for large-scale photonic quantum information processing.

10.
Acta Neurochir Suppl ; 122: 323-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27165930

RESUMEN

Intracranial pressure (ICP) is routinely measured in patients with severe traumatic brain injury (TBI). We describe a novel technique that allowed us to monitor intraspinal pressure (ISP) at the injury site in 14 patients who had severe acute traumatic spinal cord injury (TSCI), analogous to monitoring ICP after brain injury. A Codman probe was inserted subdurally to measure the pressure of the injured spinal cord compressed against the surrounding dura. Our key finding is that it is feasible and safe to monitor ISP for up to a week in patients after TSCI, starting within 72 h of the injury. With practice, probe insertion and calibration take less than 10 min. The ISP signal characteristics after TSCI were similar to the ICP signal characteristics recorded after TBI. Importantly, there were no associated complications. Future studies are required to determine whether reducing ISP improves neurological outcome after severe TSCI.


Asunto(s)
Monitoreo Fisiológico , Presión , Traumatismos de la Médula Espinal/fisiopatología , Médula Espinal/irrigación sanguínea , Espacio Subdural , Adolescente , Adulto , Anciano , Presión Arterial , Vértebras Cervicales/cirugía , Estudios de Factibilidad , Femenino , Humanos , Presión Intracraneal , Laminectomía , Masculino , Persona de Mediana Edad , Tornillos Pediculares , Traumatismos de la Médula Espinal/complicaciones , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/cirugía , Fusión Vertebral , Vértebras Torácicas/cirugía , Adulto Joven
11.
Acta Neurochir Suppl ; 122: 335-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27165932

RESUMEN

Following a traumatic brain injury (TBI), intracranial pressure (ICP) increases, often resulting in secondary brain insults. After a spinal cord injury, here the cord may be swollen, leading to a local increase in intraspinal pressure (ISP). We hypothesised that waveform analysis methodology similar to that used for ICP after TBI may be applicable for the monitoring of patients with spinal cord injury.An initial cohort of 10 patients with spinal cord injury, as presented by the first author at a meeting in Cambridge in May 2012, were included in this observational study. The whole group (18 patients) was recently presented in the context of clinically oriented findings (Werndle et al., Crit Care Med, 42(3):646-655, 2014, PMID: 24231762). Mean pressure, pulse and respiratory waveform were analysed along slow vasogenic waves.Slow, respiratory and pulse components of ISP were characterised in the time and frequency domains. Mean ISP was 22.5 ± 5.1, mean pulse amplitude 1.57 ± 0.97, mean respiratory amplitude 0.65 ± 0.45 and mean magnitude of slow waves (a 20-s to 3-min period) was 3.97 ± 3.1 (all in millimetres of mercury). With increasing mean ISP, the pulse amplitude increased in all cases. This suggests that the ISP signal is of a similar character to ICP recorded after TBI. Therefore, the methods of ICP analysis can be helpful in ISP analysis.


Asunto(s)
Presión , Traumatismos de la Médula Espinal/fisiopatología , Espacio Subdural , Estudios de Cohortes , Humanos , Presión Intracraneal , Monitoreo Fisiológico , Análisis de la Onda del Pulso , Respiración , Canal Medular
12.
Vox Sang ; 108(2): 113-22, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25234417

RESUMEN

BACKGROUND AND OBJECTIVES: Previous studies have demonstrated that transfused blood components from donors with occult hepatitis B virus infection (OBI) are potentially infectious. This study reports the results of an Australian lookback programme for the period subsequent to the commencement of individual donation HBV NAT in July 2010 and estimates the HBV transmission rate for components from two categories of donors, confirmed OBI and HBV inconclusive (anti-HBc reactive with non-discriminated NAT result). MATERIALS AND METHODS: Using the results of lookback investigations, we estimated HBV transmission rates by donor category and type of component transfused based on the prevalence of antibodies to HBV core antigen (anti-HBc) in recipients adjusted for the estimated prevalence in the general population. RESULTS: After subtracting the background anti-HBc rate, we derived an adjusted transmission rate (all components) with lower and upper bounds as follows: 0·85% (0·00-2·35%) for OBI donors, 2·83% (1·23-4·33%) for inconclusive donors and 1·81% (0·21-3·31%) for total (OBI and inconclusive) donors. The median adjusted transmission rate for total donors was higher (but not statistically) for plasma (3·01%) than RCCs (2·86%), but there was no evidence of transmission for cryoprecipitate or platelets (0% for both components). CONCLUSION: Our lookback study suggests a low (0·2-3·3%) but measurable rate of HBV transmission in Australia associated with donors with OBI and supports published evidence that at least some blood component types from OBI donors, including a proportion undetectable by ID-NAT can transmit HBV by transfusion.


Asunto(s)
Donantes de Sangre , ADN Viral/sangre , Hepatitis B/transmisión , Reacción a la Transfusión , Australia , Hepatitis B/sangre , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Humanos , Persona de Mediana Edad , Prevalencia
13.
Br J Neurosurg ; 29(6): 746-50, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26488224

RESUMEN

The NHS is entering a third decade of administrative turbulence and cost pressures and many view the new NHS structure and systems as complex and confusing. Health and social care budgets are being merged in some geographical areas and large efficiency savings are needed by 2020. There are risks that lie ahead for neurosurgery and our patients if the specialty becomes further fragmented and opportunities for positive change are missed. One of the new care models proposed in the NHS five year plan is specialist care provided across multiple hospital sites by a single overarching specialist trust, mirroring ophthalmology where the Moorfields trust provides specialist eye services in over 20 locations in London and the South East. This model lends itself to adoption by neurosurgery and has the potential to increase standards, efficiency, training and research.


Asunto(s)
Neurocirugia/tendencias , Medicina Estatal/tendencias , Investigación Biomédica , Humanos , Modelos Organizacionales , Neurocirugia/economía , Especialización , Medicina Estatal/economía , Reino Unido
14.
Crit Care Med ; 42(3): 646-55, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24231762

RESUMEN

OBJECTIVES: To develop a technique for continuously monitoring intraspinal pressure at the injury site (intraspinal pressure) after traumatic spinal cord injury. DESIGN: A pressure probe was placed subdurally at the injury site in 18 patients who had isolated severe traumatic spinal cord injury (American Spinal Injuries Association grades A-C). Intraspinal pressure monitoring started within 72 hours of the injury and continued for up to a week. In four patients, additional probes were inserted to simultaneously monitor subdural pressure below the injury and extradural pressure. Blood pressure was recorded from a radial artery catheter kept at the same horizontal level as the injured segment of the spinal cord. We determined the effect of various maneuvers on spinal cord perfusion pressure and spinal cord function and assessed using a limb motor score and motor-evoked potentials. SETTING: Neurosurgery and neuro-ICU covering a 3 million population in London. SUBJECTS: Patients with severe traumatic spinal cord injury. Control subjects without spinal cord injury (to monitor spinal cerebrospinal fluid signal and motor evoked potentials). INTERVENTIONS: Insertion of subdural spinal pressure probe. MEASUREMENTS AND MAIN RESULTS: There were no procedure-related complications. Intraspinal pressure at the injury site was higher than subdural pressure below the injury or extradural pressure. Average intraspinal pressure from the 18 patients with traumatic spinal cord injury was significantly higher than average intraspinal pressure from 12 subjects without traumatic spinal cord injury. Change in arterial PCO2, change in sevoflurane dose, and mannitol administration had no significant effect on intraspinal pressure or spinal cord perfusion pressure. Increase in inotrope dose significantly increased spinal cord perfusion pressure. Bony realignment and laminectomy did not effectively lower intraspinal pressure. Laminectomy was potentially detrimental by exposing the swollen spinal cord to compression forces applied to the skin. By intervening to increase spinal cord perfusion pressure, we could increase the amplitude of motor-evoked potentials recorded from below or just above the injury level in nine of nine patients with traumatic spinal cord injury. In two of two patients with American Spinal Injuries Association grade C traumatic spinal cord injury, higher spinal cord perfusion pressure correlated with increased limb motor score. CONCLUSIONS: Our findings provide proof-of-principle that subdural intraspinal pressure at the injury site can be measured safely after traumatic spinal cord injury.


Asunto(s)
Presión Arterial/fisiología , Presión del Líquido Cefalorraquídeo/fisiología , Monitoreo Fisiológico/métodos , Traumatismos de la Médula Espinal/cirugía , Médula Espinal/irrigación sanguínea , Enfermedad Aguda , Adolescente , Adulto , Anciano , Velocidad del Flujo Sanguíneo/fisiología , Estudios de Casos y Controles , Potenciales Evocados Motores , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Unidades de Cuidados Intensivos , Laminectomía/métodos , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios/métodos , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Traumatismos de la Médula Espinal/diagnóstico , Resultado del Tratamiento , Adulto Joven
15.
Phys Rev Lett ; 113(20): 200501, 2014 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-25432032

RESUMEN

We report an experimental demonstration of a one-way implementation of a quantum algorithm solving Simon's problem-a black-box period-finding problem that has an exponential gap between the classical and quantum runtime. Using an all-optical setup and modifying the bases of single-qubit measurements on a five-qubit cluster state, key representative functions of the logical two-qubit version's black box can be queried and solved. To the best of our knowledge, this work represents the first experimental realization of the quantum algorithm solving Simon's problem. The experimental results are in excellent agreement with the theoretical model, demonstrating the successful performance of the algorithm. With a view to scaling up to larger numbers of qubits, we analyze the resource requirements for an n-qubit version. This work helps highlight how one-way quantum computing provides a practical route to experimentally investigating the quantum-classical gap in the query complexity model.

16.
Ann Neurol ; 71(3): 323-33, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22374891

RESUMEN

OBJECTIVE: Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system associated with pathogenic autoantibodies against the astrocyte water channel protein aquaporin-4 (AQP4). The presence of neutrophils is a characteristic feature in NMO lesions in humans. Neutrophils are not generally found in multiple sclerosis lesions. We evaluated the role of neutrophils in a mouse NMO model. METHODS: NMO lesions were produced in mice by intracerebral injection of immunoglobulin G (IgG) isolated from NMO patient serum and human complement. We previously reported that this mouse model produces the characteristic histological features of NMO, including perivascular complement activation, inflammatory cell infiltration, and loss of myelin, AQP4, and glial fibrillary acidic protein. Lesions are absent when AQP4 null mice are used or when IgG from non-NMO patients is injected. RESULTS: We found remarkably reduced neuroinflammation, myelin loss, and AQP4 loss in brains of neutropenic mice at 24 hours and 7 days, and increased severity of NMO lesions in mice made neutrophilic by granulocyte colony stimulating factor. NMO lesions were greatly reduced by intracerebral administration of the neutrophil protease inhibitors Sivelestat and cathepsin G inhibitor I or by intraperitoneal injection of Sivelestat alone. Immunostaining of human NMO lesions for neutrophil elastase revealed many degranulating perivascular neutrophils, with no equivalent perivascular neutrophils in human multiple sclerosis lesions. INTERPRETATION: Our data implicate a central role of neutrophils in the pathogenesis of early NMO lesions and suggest the potential utility of neutrophil protease inhibitors such as Sivelestat in NMO therapy.


Asunto(s)
Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Inmunoglobulina G/toxicidad , Neuromielitis Óptica/tratamiento farmacológico , Neuromielitis Óptica/patología , Neutrófilos/efectos de los fármacos , Inhibidores de Proteasas/uso terapéutico , Animales , Encéfalo/patología , Humanos , Ratones , Ratones Noqueados , Neuromielitis Óptica/enzimología , Neutrófilos/enzimología , Neutrófilos/patología , Inhibidores de Proteasas/farmacología
17.
Biophys J ; 102(6): 1303-12, 2012 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-22455913

RESUMEN

Mechanical signals transferred between a cell and its extracellular matrix play an important role in regulating fundamental cell behavior. To further define the complex mechanical interactions between cells and matrix from a multiscale perspective, a biaxial testing device was designed and built. Finite element analysis was used to optimize the cruciform specimen geometry so that stresses within the central region were concentrated and homogenous while minimizing shear and grip effects. This system was used to apply an equibiaxial loading and unloading regimen to fibroblast-seeded tissue equivalents. Digital image correlation and spot tracking were used to calculate three-dimensional strains and associated strain transfer ratios at macro (construct), meso, matrix (collagen fibril), cell (mitochondria), and nuclear levels. At meso and matrix levels, strains in the 1- and 2-direction were statistically similar throughout the loading-unloading cycle. Interestingly, a significant amplification of cellular and nuclear strains was observed in the direction perpendicular to the cell axis. Findings indicate that strain transfer is dependent upon local anisotropies generated by the cell-matrix force balance. Such multiscale approaches to tissue mechanics will assist in advancement of modern biomechanical theories as well as development and optimization of preconditioning regimens for functional engineered tissue constructs.


Asunto(s)
Estrés Mecánico , Ingeniería de Tejidos/instrumentación , Diseño de Equipo , Espacio Extracelular/metabolismo , Fibroblastos/citología , Fibroblastos/metabolismo , Microscopía Fluorescente , Andamios del Tejido/química
18.
Anal Bioanal Chem ; 403(10): 3051-6, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22566198

RESUMEN

Anthelmintic drugs are used in clinical and veterinary practice for the treatment of infections caused by parasitic worms. Their extensive use in food-producing animals can cause the presence of residues in food. For consumer protection it is necessary to monitor the levels of anthelmintic residues to ensure that they remain within the legally permitted maximum acceptable concentrations. For this purpose, the use of multiplex screening methods is advantageous. Biochip array technology allows the simultaneous determination of multiple analytes from a single sample at a single point in time. This study reports the development of an Evidence biochip array for the multiplex screening of anthelmintic drugs. Simultaneous competitive chemiluminescent immunoassays are employed. The solid support and vessel is the biochip, which contains an array of discrete test sites. The assays were applied to the semiautomated bench-top analyser Evidence Investigator. The aminobenzimidazoles assay detected aminomebendazole, albendazole 2-aminosulphone and aminoflubendazole, the avermectins assay detected emamectin benzoate, eprinomectin, abamectin, ivermectin and doramectin, the benzimidazoles assay detected albendazole sulphone, albendazole, albendazole sulphoxide, oxibendazole, oxfendazole and flubendazole, the thiabendazole assay detected cambendazole, thiabendazole and 5-hydroxythiabendazole and the triclabendazole assay detected ketotriclabendazole, triclabendazole and triclabendazole sulphoxide. The limits of detection ranged from 0.3 ppb (aminobenzimidazoles) to 2.0 ppb (levamisole) in milk and from 0.15 ppb (aminobenzimidazoles) to 6.5 ppb (levamisole) in tissue. The average recovery range was 71-135 %. This multianalytical approach on a biochip platform is applicable to the screening of more than 20 anthelmintic drugs in different food matrices, leading to consolidation of tests and enhancement of the test result output.


Asunto(s)
Antihelmínticos/análisis , Evaluación Preclínica de Medicamentos/métodos , Análisis por Micromatrices/métodos , Animales , Bovinos , Inmunoensayo/métodos , Indicadores y Reactivos , Mediciones Luminiscentes/métodos , Leche/química
19.
Gen Comp Endocrinol ; 175(3): 464-72, 2012 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-22197209

RESUMEN

Urinary hormone analysis has proved accurate for identifying sex and breeding periods in dimorphic amphibians with known reproductive cycles. We examined whether these techniques could provide this much needed information for a monomorphic anuran with an unconfirmed mating season in the wild. We analysed urinary estrone conjugate, testosterone, and progesterone metabolites to infer the time of breeding and to identify sex in the endangered Maud Island frog, Leiopelma pakeka. Testosterone metabolites in males and estrone and progesterone metabolites in females were at their peak during winter for both wild and captive frogs. These urinary metabolite patterns were consistent with the high proportion of females exhibiting enlarged ovarian follicles in winter months. Sex identification based on urinary estrone metabolite levels was 94% correct in this monomorphic species, in which the sexes overlap in snout-to-vent length (SVL) for over half of their adult size range and in which no other sexually dimorphic trait is known. The seasonal profiles imply unexpected winter or early spring breeding in L. pakeka. Overall, these results demonstrate use of urinary hormone metabolites for reproductive monitoring and sex identification in one of the world's most threatened and evolutionarily distinct amphibians.


Asunto(s)
Anuros/metabolismo , Cruzamiento , Estrona/orina , Progesterona/orina , Estaciones del Año , Caracteres Sexuales , Testosterona/orina , Animales , Femenino , Masculino , Folículo Ovárico/anatomía & histología , Reproducción/fisiología , Conducta Sexual Animal/fisiología
20.
NMR Biomed ; 24(1): 54-60, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20665905

RESUMEN

In a prospective study, patients with a radiologically proven brain tumour underwent diffusion tensor imaging (DTI) prior to definitive diagnosis and treatment. Twenty-eight patients with a histologically proven glioblastoma or metastasis were included in the study. Following the definition of regions of interest, DTI metrics [mean diffusivity (MD) and fractional anisotropy (FA)] were calculated for the tumour volume and the surrounding region of peritumoral oedema. These metrics were then subjected to logistic regression to investigate their ability to discriminate between glioblastomas and cerebral metastases. A cross-validation was performed to investigate the ability of the model to predict tumour. The logistic regression analysis correctly distinguished glioblastoma in 15 of 16 cases (93.8%) and metastasis in 11 of 12 cases (91.7%). Cross-validation resulted in the model correctly predicting 14 of 16 (87.5%) glioblastomas and 10 of 12 (83.3%) metastases studied. MD was significantly higher (p = 0.02) and FA was significantly lower (p = 0.04) within the oedema surrounding metastases than within the oedema around glioblastomas. MD was significantly higher (p = 0.02) within the tumour volume of the glioblastomas. Our results demonstrate that, when DTI metrics from the tumour volume and surrounding peritumoral oedema are studied in combination, glioblastoma can be reliably discriminated from cerebral metastases.


Asunto(s)
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/secundario , Imagen de Difusión Tensora/métodos , Glioblastoma/diagnóstico , Adulto , Anciano , Anisotropía , Neoplasias Encefálicas/patología , Diagnóstico Diferencial , Femenino , Glioblastoma/patología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Carga Tumoral
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