The changes in pain which mediate Reductions in fatigue likely reflect central not peripheral mechanisms : Results from the BSRBR-RA

Peer reviewed

Peripheral refraction validity of the Shin-Nippon SRW5000 autorefractor

PURPOSE: To investigate the operation of the Shin-Nippon/Grand Seiko autorefractor and whether higher-order aberrations affect its peripheral refraction measurements. METHODS: Information on instrument design, together with parameters and equations used to obtain refraction, was obtained from a patent. A model eye simulating the operating principles was tested with an optical design program. Effects of induced defocus and astigmatism on the retinal image were used to calibrate the model eye to match the patent equations. Coma and trefoil were added to assess their effects on the image. Peripheral refraction of a physical model eye was measured along four visual field meridians with the Shin-Nippon/Grand Seiko autorefractor SRW-5000 and a Hartmann-Shack aberrometer, and simulated autorefractor peripheral refraction was derived using the Zernike coefficients from the aberrometer. RESULTS: In simulation, the autorefractor's square image was changed in size by defocus, into rectangles or parallelograms by astigmatism, and into irregular shapes by coma and trefoil. In the presence of 1.0 D oblique astigmatism, errors in refraction were proportional to the higher-order aberrations, with up to 0.8 D sphere and 1.5 D cylinder for ±0.6 μm of coma or trefoil coefficients with a 5-mm-diameter pupil. For the physical model eye, refraction with the aberrometer was similar in all visual field meridians, but refraction with the autorefractor changed more quickly along one oblique meridian and less quickly along the other oblique meridian than along the horizontal and vertical meridians. Simulations predicted that higher-order aberrations would affect refraction in oblique meridians, and this was supported by the experimental measurements with the physical model eye. CONCLUSIONS: The autorefractor's peripheral refraction measurements are valid for horizontal and vertical field meridians, but not for oblique field meridians. Similar instruments must be validated before being adopted outside their design scope.

Enhancing the Visualization of the Peripheral Retina with Wide Field-of-View Optical Coherence Tomography

The goal of my Ph.D. thesis is to enhance the visualization of the peripheral retina using wide-field optical coherence tomography (OCT) in a clinical setting.

OCT has gain widespread adoption in clinical ophthalmology due to its ability to visualize the diseases of the macula and central retina in three-dimensions, however, clinical OCT has a limited field-of-view of 300. There has been increasing interest to obtain high-resolution images outside of this narrow field-of-view, because three-dimensional imaging of the peripheral retina may prove to be important in the early detection of neurodegenerative diseases, such as Alzheimer's and dementia, and the monitoring of known ocular diseases, such as diabetic retinopathy, retinal vein occlusions, and choroid masses.

Before attempting to build a wide-field OCT system, we need to better understand the peripheral optics of the human eye. Shack-Hartmann wavefront sensors are commonly used tools for measuring the optical imperfections of the eye, but their acquisition speed is limited by their underlying camera hardware. The first aim of my thesis research is to create a fast method of ocular wavefront sensing such that we can measure the wavefront aberrations at numerous points across a wide visual field. In order to address aim one, we will develop a sparse Zernike reconstruction technique (SPARZER) that will enable Shack-Hartmann wavefront sensors to use as little as 1/10th of the data that would normally be required for an accurate wavefront reading. If less data needs to be acquired, then we can increase the speed at which wavefronts can be recorded.

For my second aim, we will create a sophisticated optical model that reproduces the measured aberrations of the human eye. If we know how the average eye's optics distort light, then we can engineer ophthalmic imaging systems that preemptively cancel inherent ocular aberrations. This invention will help the retinal imaging community to design systems that are capable of acquiring high resolution images across a wide visual field. The proposed model eye is also of interest to the field of vision science as it aids in the study of how anatomy affects visual performance in the peripheral retina.

Using the optical model from aim two, we will design and reduce to practice a clinical OCT system that is capable of imaging a large (800) field-of-view with enhanced visualization of the peripheral retina. A key aspect of this third and final aim is to make the imaging system compatible with standard clinical practices. To this end, we will incorporate sensorless adaptive optics in order to correct the inter- and intra- patient variability in ophthalmic aberrations. Sensorless adaptive optics will improve both the brightness (signal) and clarity (resolution) of features in the peripheral retina without affecting the size of the imaging system.

The proposed work should not only be a noteworthy contribution to the ophthalmic and engineering communities, but it should strengthen our existing collaborations with the Duke Eye Center by advancing their capability to diagnose pathologies of the peripheral retinal.

Changes in Brain Resting-state Functional Connectivity Associated with Peripheral Nerve Block: A Pilot Study.

BACKGROUND: Limited information exists on the effects of temporary functional deafferentation (TFD) on brain activity after peripheral nerve block (PNB) in healthy humans. Increasingly, resting-state functional connectivity (RSFC) is being used to study brain activity and organization. The purpose of this study was to test the hypothesis that TFD through PNB will influence changes in RSFC plasticity in central sensorimotor functional brain networks in healthy human participants. METHODS: The authors achieved TFD using a supraclavicular PNB model with 10 healthy human participants undergoing functional connectivity magnetic resonance imaging before PNB, during active PNB, and during PNB recovery. RSFC differences among study conditions were determined by multiple-comparison-corrected (false discovery rate-corrected P value less than 0.05) random-effects, between-condition, and seed-to-voxel analyses using the left and right manual motor regions. RESULTS: The results of this pilot study demonstrated disruption of interhemispheric left-to-right manual motor region RSFC (e.g., mean Fisher-transformed z [effect size] at pre-PNB 1.05 vs. 0.55 during PNB) but preservation of intrahemispheric RSFC of these regions during PNB. Additionally, there was increased RSFC between the left motor region of interest (PNB-affected area) and bilateral higher order visual cortex regions after clinical PNB resolution (e.g., Fisher z between left motor region of interest and right and left lingual gyrus regions during PNB, -0.1 and -0.6 vs. 0.22 and 0.18 after PNB resolution, respectively). CONCLUSIONS: This pilot study provides evidence that PNB has features consistent with other models of deafferentation, making it a potentially useful approach to investigate brain plasticity. The findings provide insight into RSFC of sensorimotor functional brain networks during PNB and PNB recovery and support modulation of the sensory-motor integration feedback loop as a mechanism for explaining the behavioral correlates of peripherally induced TFD through PNB.

Nerve localization techniques for peripheral nerve block and possible future directions

Ultrasound guidance is now a standard nerve localization technique for peripheral nerve block (PNB). Ultrasonography allows simultaneous visualization of the target nerve, needle, local anesthetic injectate and surrounding anatomical structures. Accurate deposition of local anesthetic next to the nerve is essential to the success of the nerve block procedure. Unfortunately, due to limitations in the visibility of both needle tip and nerve surface, the precise relationship between needle tip and target nerve is unknown at the moment of injection. Importantly, nerve injury may result both from an inappropriately placed needle tip and inappropriately placed local anesthetic. The relationship between the block needle tip and target nerve is of paramount importance to the safe conduct of peripheral nerve block. This review summarizes the evolution of nerve localization in regional anesthesia, characterizes a problem faced by clinicians in performing ultrasound guided nerve block and explores the potential technological solutions to this problem.

Individual Variation in VO2peak Response Following Sprint Interval Training: The Role of Peripheral Adaptation

There is a large degree of heterogeneity in response to regular physical activity at the individual level, with some exhibiting no or very small improvements in VO2peak following highly controlled exercise training. The purpose of this thesis was to examine individual variation in VO2peak response to sprint interval training (SIT) in relation to individual responses to multiple measures of peripheral physiological adaptation. Specifically, VO2peak, capillary density, fibre-specific SDH content, and type I fibre % were measured in 23 young, healthy, recreationally active males before and after 4 weeks SIT (Tabata protocol 4 x per week). The key findings of this experiment included that, when separated into tertiles of VO2peak response, the high (HI) and low (LO) groups differed significantly in VO2peak change after training. Secondly, there was no difference between HI and LO groups for response in any of capillary density, fibre-specific SDH content, or fibre type %, with no correlation found between individual VO2peak response and changes in any measured peripheral variable. Together, these results confirm that individuals respond heterogeneously to SIT and suggest that this heterogeneity does not result from differences in individual changes in capillary density, fibre-specific SDH content or type I fibre %. It is speculated that some other combination of peripheral physiological adaptation must explain variability in VO2peak response to 4 weeks of SIT.

Gene scanning of VDJH-amplified segments is a clinically relevant technique to detect contaminating tumor cells in the apheresis products of multiple myeloma patients undergoing autologous peripheral blood stem cell transplantation.

Contaminating tumour cells in apheresis products have proved to influence the outcome of patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (APBSCT). The gene scanning of clonally rearranged VDJ segments of the heavy chain immunoglobulin gene (VDJH) is a reproducible and easy to perform technique that can be optimised for clinical laboratories. We used it to analyse the aphereses of 27 MM patients undergoing APBSCT with clonally detectable VDJH segments, and 14 of them yielded monoclonal peaks in at least one apheresis product. The presence of positive results was not related to any pre-transplant characteristics, except the age at diagnosis (lower in patients with negative products, P = 0.04). Moreover, a better pre-transplant response trended to associate with a negative result (P = 0.069). Patients with clonally free products were more likely to obtain a better response to transplant (complete remission, 54% vs 28%; >90% reduction in the M-component, 93% vs 43% P = 0.028). In addition, patients transplanted with polyclonal products had longer progression-free survival, (39 vs 19 months, P = 0.037) and overall survival (81% vs 28% at 5 years, P = 0.045) than those transplanted with monoclonal apheresis. In summary, the gene scanning of apheresis products is a useful and clinically relevant technique in MM transplanted patients.

The detection of contaminating clonal cells in apheresis products is related to response and outcome in multiple myeloma undergoing autologous peripheral blood stem cell transplantation.

In the present paper, we report on the use of the heteroduplex PCR technique to detect the presence of clonally rearranged VDJ segments of the heavy chain immunoglobulin gene (VDJH) in the apheresis products of patients with multiple myeloma (MM) undergoing autologous peripheral blood stem cell (APBSC) transplantation. Twenty-three out of 31 MM patients undergoing APBSC transplantation with VDJH segments clonally rearranged detected at diagnosis were included in the study. Samples of the apheresis products were PCR amplified using JH and VH (FRIII and FRII) consensus primers and subsequently analyzed with the heteroduplex technique, and compared with those obtained at diagnosis. 52% of cases yielded positive results (presence of clonally rearranged VDJH segments in at least one apheresis). The presence of positive results in the apheresis products was not related to any pretransplant characteristics with the exception of response status at transplant. Thus, while no one patient with positive apheresis products was in complete remission (CR), negative immunofixation, before the transplant, five cases (46%) with negative apheresis were already in CR at transplant (P = 0.01). The remaining six cases with heteroduplex PCR negative apheresis were in partial remission before transplant. Patients with clonally free products were more likely to obtain CR following transplant (64% vs 17%, P= 0.02) and a longer progression-free survival, (40 months in patients transplanted with polyclonal products vs 20 with monoclonal ones, P = 0.03). These results were consistent when the overall survival was considered, since it was better in those patients with negative apheresis than it was in those with positive (83% vs 36% at 5 years from diagnosis, P= 0.01). These findings indicate that the presence of clonality rearranged VDJH segments is related to the response and outcome in MM transplanted patients.

Avaliação das capacitações de Hanseníase: enfermeiros opinião de médicos e enfermeiros das equipes de saúde da família

MORENO,Cléa Maria da Costa,ENDERS,Bertha Cruz, SIMPSON, Clélia Albino. Avaliação das capacitações de Hanseníase: enfermeiros opinião de médicos e enfermeiros das equipes de saúde da família. Revista Brasileira de Enfermagem, Brasília, v.61,n.esp.p. 671-5.2008.

Peripheral Artery Disease Patients May Benefit More from Aggressive Secondary Prevention than Aneurysm Patients to Improve Survival

BACKGROUND AND AIMS: Although it has become clear that aneurysmal and occlusive arterial disease represent two distinct etiologic entities, it is still unknown whether the two vascular pathologies are prognostically different. We aim to assess the long-term vital prognosis of patients with abdominal aortic aneurysmal disease (AAA) or peripheral artery disease (PAD), focusing on possible differences in survival, prognostic risk profiles and causes of death. METHODS: Patients undergoing elective surgery for isolated AAA or PAD between 2003 and 2011 were retrospectively included. Differences in postoperative survival were determined using Kaplan-Meier and Cox regression analysis. Prognostic risk profiles were also established with Cox regression analysis. RESULTS: 429 and 338 patients were included in the AAA and PAD groups, respectively. AAA patients were older (71.7 vs. 63.3 years, p < 0.001), yet overall survival following surgery did not differ (HR: 1.16, 95% CI: 0.87-1.54). Neither was type of vascular disease associated with postoperative cardiovascular nor cancer-related death. However, in comparison with age- and gender-matched general populations, cardiovascular mortality was higher in PAD than AAA patients (48.3% vs. 17.3%). Survival of AAA and PAD patients was negatively affected by age, history of cancer and renal insufficiency. Additional determinants in the PAD group were diabetes and ischemic heart disease. CONCLUSIONS: Long-term survival after surgery for PAD and AAA is similar. However, overall life expectancy is significantly worse among PAD patients. The contribution of cardiovascular disease towards mortality in PAD patients warrants more aggressive secondary prevention to reduce cardiovascular mortality and improve longevity.

Avaliação das capacitações de Hanseníase: enfermeiros opinião de médicos e enfermeiros das equipes de saúde da família

MORENO,Cléa Maria da Costa,ENDERS,Bertha Cruz, SIMPSON, Clélia Albino. Avaliação das capacitações de Hanseníase: enfermeiros opinião de médicos e enfermeiros das equipes de saúde da família. Revista Brasileira de Enfermagem, Brasília, v.61,n.esp.p. 671-5.2008.

Protemic characterization of peripheral blood mononuclear cells

Peripheral blood mononuclear cells (PBMCs) play quite diverse and important roles in monitoring immune homeostasis. Thus, these subset of blood cells may provide access to potential physiological relevant biomolecules, namely proteins. For this reason, PBMCs represent a promising biological sample in scientific research, particularly as a source of potential biological markers discovery of the most diverse diseases. Prior studies of proteomic characterization of PBMCs from healthy individuals lack either the identification of a large number of proteins or its quantification in a way that is compatible with the search of potential biomarker candidates. Therefore, this study aimed to provide a comprehensive PBMCs proteome characterisation as well as to create a SWATH library. It was also evaluated if by using the BD Vacutainer® CPT™ tubes for PBMCs isolation, it would be possible to identify a larger number of immunologically relevant proteins in comparison to plasma samples. The enrichment test assay revealed that it is possible to identify more immune-related proteins from isolated PBMCs than from plasma. Moreover, the majority of the quantified proteins with an “immune system” GO term assigned is present in higher amounts in PBMCs samples. 2D LC-MS/MS proved to be the best approach to use in qualitative analysis of PBMCs and in the construction of a SWATH library, since it resulted in an increase of both identified and quantified proteins (66.3% and 16.9%, respectively) in comparison to 1D LC-MS/MS. A total of 2071 proteins were identified and it was possible to quantify 922 different proteins among six distinct samples. From these proteins, 445 were commom between all individuals. In conclusion, this work provides a comprehensive PBMCs proteome dataset that will be useful in further studies that focus on the search for potential biological markers of various pathologies in these cells. Additionally, SWATH-MS proved to be a reproducible and effective acquisition method to quantify PBMCs proteins.

Improving interfaces for nerve repair

Autologous nerve grafts are the current gold standard for the repair of peripheral nerve injuries. However, there is a need to develop an alternative to this technique, as donor-site morbidities such as neuroma formation and permanent loss of function are a few of the limitations concerned with this technique. Artificial nerve conduits have therefore emerged as an alternative for the repair of short peripheral nerve defects of less than 30 mm, however they do not surpass autologous nerve grafts clinically. To develop a nerve conduit that supports regeneration over long nerve gaps and in large diameter nerves, researchers have focused on functionalizing of the conduits by studying the components that enhance nerve regeneration such as micro/nano-topography, growth factor delivery systems, supportive cells and extracellular matrix (ECM) proteins as well as understanding the complex biological reactions that take place during peripheral nerve regeneration. This thesis presents strategies to improve peripheral nerve interfaces to better the regenerative potential by using dorsal root ganglions (DRGs) isolated from neonatal rats as an in vitro model of nerve regeneration. The work started off by investigating the usefulness of a frog foam protein Ranaspumin-2 (Rsn2) to coat biomaterials for compatibility, this lead to the discovery of temporary cell adhesion on polydimethylsiloxane (PDMS), which was investigated as a suitable tool to derive cell-sheets for nerve repair. The influence of Rsn2 anchored to specific adhesion peptide sequences, such as isoleucine-lysine-valine-alanine-valine (IKVAV), a sequence derived from laminin proven to promote cell adhesion and neurite outgrowth, was tested as a useful means to influence nerve regeneration. This approach improves the axonal outgrowth and maintains outgrowth long term. Based on the hypothesis that combinational modulation of substrate topography, stiffness and neurotrophic support, affects axonal outgrowth in whole DRGs, dissociated DRGs were used to assess if these factors similarly act at the single cell level. Rho associated protein kinase (ROCK) and myosin II inhibitors, which affect cytoskeletal contractility, were used to influence growth cone traction forces and have shown that these factors work in combination by interfering with growth cone dynamic creating a different response in axonal outgrowth at the single cell level.