Alterations in Circulating Immune Cells in Neovascular Age-Related Macular Degeneration

Neovascular age-related macular degeneration (nAMD) is the leading cause of irreversible blindness in developed countries. Recent advances have highlighted the essential role of inflammation in the development of the disease. In addition to local retinal chronic inflammatory response, systemic immune alterations have also been observed in AMD patients. In this study we investigated the association between the frequency of circulating leukocyte populations and the prevalence as well as clinical presentations of nAMD. Leukocyte subsets of 103 nAMD patients (most of them were receiving anti-VEGF therapy prior to enrolment) and 26 controls were analysed by flow cytometry by relative cell size, granularity and surface markers. Circulating CD11b(+) cells and CD16(hi)HLA-DR(-) neutrophils were significantly increased (P = 0.015 and 0.009 respectively) in nAMD when compared to controls. The percentage of circulating CD4(+) T-cells was reduced in nAMD patients without subretinal fibrosis (P = 0.026) compared to patients with subretinal fibrosis. There was no correlation between the percentage of circulating leukocytes and the responsiveness to anti-VEGF therapy in nAMD patients. Our results suggest that higher levels of circulating CD11b(+) cells and neutrophils are associated with nAMD and that reduced levels of CD4(+) T-cells are associated with the absence of subretinal fibrosis in nAMD.

Preoperative radial artery volume flow is predictive of arteriovenous fistula outcomes

Objective: Guidelines recommend the creation of a wrist radiocephalic arteriovenous fistula (RAVF) as initial hemodialysis vascular access. This study explored the potential of preoperative ultrasound vessel measurements to predict AVF failure to mature (FTM) in a cohort of patients with end-stage renal disease in Northern Ireland

.Methods: A retrospective analysis was performed of all patients who had preoperative ultrasound mapping of upper limb blood vessels carried out from August 2011 to December 2014 and whose AVF reached a functional outcome by March 2015.

Results: There were 152 patients (97% white) who had ultrasound mapping andan AVF functional outcome recorded; 80 (54%) had an upper arm AVF created, and 69 (46%) had a RAVF formed. Logistic regression revealed that female gender (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.12-5.55; P = .025), minimum venous diameter (OR, 0.6; 95% CI, 0.39-0.95; P = .029), and RAVF (OR, 0.4; 95% CI, 0.18-0.89; P = .026) were associated with FTM. On subgroup analysis of the RAVF group, RAVFs with an arterial volume flow <50 mL/min were seven times as likely to fail as RAVFs with higher volume flows (OR, 7.0; 95% CI, 2.35-20.87; P < .001).

Conclusions: In this cohort, a radial artery flow rate <50 mL/min was associated with a sevenfold increased risk of FTM in RAVF, which to our knowledge has not been previously reported in the literature. Preoperative ultrasound mapping adds objective assessment in the clinical prediction of AVF FTM.

Multiple Markers of Inflammation in Crevicular Fluid During Experimental Gingivitis

Objective: To evaluate temporal changes in GCF levels of substance P, cathepsin G, interleukin 1 beta (IL-1&beta), neutrophil elastase and alpha1-antitrypsin (&alpha1AT) during development of and recovery from experimental gingivitis. Methods: Healthy human volunteers participated in a split-mouth study: experimental gingivitis was induced using a soft vinyl splint to cover test teeth during brushing over 21 days, after which normal brushing was resumed. Modified gingival index (MGI), gingival bleeding index (BI) and modified Quigley and Hein plaque index (PI) were assessed and 30-second GCF samples taken from 4 paired test and contra-lateral control sites in each subject at days 0, 7, 14, 21, 28 and 42. GCF volume was measured and site-specific quantification of one analyte per GCF sample was performed using radioimmunoassay (substance P), enzyme assay (cathepsin G) or ELISA (IL-1&beta, elastase, &alpha1AT). Site-specific data were analysed using analysis of repeated measurements and paired sample tests. Results: 56 subjects completed the study. All measurements at baseline (day 0) and at control sites throughout the study were low. Clinical indices and GCF volumes at the test sites increased from day 0, peaking at day 21 (difference between test and control for PI, BI, MGI and GCF all p<0.0001) and decreased again to control levels by day 28. Levels of four inflammatory markers showed a similar pattern, with significant differences between test and control apparent at 7 days (substance P p=0.0015; cathepsin G p=0.029; IL-1&beta p=0.026; elastase p=0.0129) and peaking at day 21 (substance P p=0.0023; cathepsin G, IL-1&beta and elastase all p<0.0001). Levels of &alpha1AT showed no apparent pattern over the course of the study. Conclusion: GCF levels of substance P, cathepsin G, IL-1&beta and neutrophil elastase have the potential to act as early markers of experimentally-induced gingival inflammation.

Pupil constriction can alter the accuracy of dark room provocative test.

BACKGROUND: Primary angle-closure glaucoma (PACG) is a major cause of visual morbidity in East Asia. Dark-room provocative test (DRPT) has been used to determine which narrow angles have the risk to develop angle closure. However, the accuracy of DRPT might be altered because that after emerging from the dark room, the configuration of the angle is affected by the light of the slit-lamp and the appositionally closed angle reopens. The aim of this study was to examine the pupillary diameter in different light conditions and use it as a parameter to assess the accuracy of dark-room provocative test. METHODS: Patients with suspected primary angle-closure glaucoma undergoing DRPT were recruited. The anterior chamber angle was examined by anterior segment optical coherence tomography under the following conditions: (1) in standard room illumination; (2) after short-term dark-adaptation and (3) after DRPT. Mean values of pupil size and numbers of appositionally closed angle under different conditions were compared. RESULTS: A total of 47 eyes of 47 patients were analyzed. The pupil size after DRPT was smaller than that after short-term dark-adaptation (P < 0.001) and smaller than that in standard room illumination (P = 0.026). The numbers of appositionally closed angles after short-term dark-adaptation were significantly larger than those after DRPT (P < 0.001). There was no significant difference between the numbers of appositionally closed angles in standard room illumination and after DRPT (P = 0.157). CONCLUSIONS: Constriction of pupil size immediately after prolonged dark room provocative test may lead to change in the angle configuration, which may lead to false negative results. We suggest a modified protocol of recording intraocular pressure immediately after DRPT and performing gonioscopy following short-term dark adaptation to improve the accuracy of angle closure assessment.

A comparison between accelerated hypofractionation and stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer (NSCLC): Results of a propensity score-matched analysis

BACKGROUND AND PURPOSE: Stereotactic ablative radiotherapy (SABR) has become standard for inoperable early-stage non-small cell lung cancer (NSCLC). However, there is no randomized evidence demonstrating benefit over more fractionated radiotherapy. We compared accelerated hypofractionation (AH) and SABR using a propensity score-matched analysis.

MATERIALS AND METHODS: From 1997-2007, 119 patients (T1-3N0M0 NSCLC) were treated with AH (48-60Gy, 12-15 fractions). Prior to SABR, this represented our institutional standard. From 2008-2012, 192 patients (T1-3N0M0 NSCLC) were treated with SABR (48-52Gy, 4-5 fractions). A total of 114 patients (57 per cohort) were matched (1:1 ratio, caliper: 0.10) using propensity scores.

RESULTS: Median follow-up (range) for the AH cohort was 36.3 (2.5-109.1) months, while that for the SABR group was 32.5 (0.3-62.6)months. Three-year overall survival (OS) and local control (LC) rates were 49.5% vs. 72.4% [p=0.024; hazard ratio (HR): 2.33 (1.28, 4.23), p=0.006] and 71.9% vs. 89.3% [p=0.077; HR: 5.56 (1.53, 20.2), p=0.009], respectively. On multivariable analysis, tumour diameter and PET staging were predictive for OS, while the only predictive factor for LC was treatment cohort.

CONCLUSIONS: OS and LC were improved with SABR, although OS is more closely related to non-treatment factors. This represents one of the few studies comparing AH to SABR for early-stage lung cancer.

Microneedle-mediated delivery of donepezil: Potential for improved treatment options in Alzheimer's disease

Transdermal drug delivery is an attractive route of drug administration, however there are relatively few marketed transdermal products. To increase delivery across the skin, strategies to enhance skin permeability are widely investigated, with microneedles demonstrating particular promise. Hydrogel-forming microneedles are inserted into the skin, and following dissolution of a drug loaded reservoir and movement of the drug through the created channels, the microneedle array is removed intact, and can then be readily and safely discarded. This study presents the formulation and evaluation of an integrated microneedle patch containing the Alzheimer's drug, donepezil hydrochloride. The integrated patch consisted of hydrogel-forming microneedles in combination with a donepezil hydrochloride containing film. Formulation and characterisation of plasticised films, prepared from poly(vinylpyrrolidone) or poly (methyl vinyl ether co-maleic anhydride/acid) (Gantrez(®)) polymers, is presented. Furthermore, in vitro permeation of donepezil hydrochloride across neonatal porcine skin from the patches was investigated, with 854.71 μg ± 122.71 μg donepezil hydrochloride delivered after 24 h, using the optimum patch formulation. Following administration of the patch to an animal model, plasma concentrations of 51.8 ± 17.6 ng/mL were obtained, demonstrating the success of this delivery platform for donepezil hydrochloride.

High Resolution measurement and mapping of tungstate in waters, soils and sediments using the low-disturbance DGT sampling technique.

Increasing tungsten (W) use for industrial and military applications has resulted in greater W discharge into natural waters, soils and sediments. Risk modeling of W transport and fate in the environment relies on measurement of the release/mobilization flux of W in the bulk media and the interfaces between matrix compartments. Diffusive gradients in thin-films (DGT) is a promising passive sampling technique to acquire such information. DGT devices equipped with the newly developed high-resolution binding gels (precipitated zirconia, PZ, or ferrihydrite, PF, gels) or classic/conventional ferrihydrite slurry gel were comprehensively assessed for measuring W in waters. FerrihydriteDGT can measure W at various ionic strengths (0.001–0.5 mol L−1 NaNO3) and pH (4–8), while PZDGT can operate across slightly wider environmental conditions. The three DGT configurations gave comparable results for soil W measurement, showing that typically W resupply is relatively poorly sustained. 1D and 2D high-resolution W profiling across sediment—water and hotspot—bulk media interfaces from Lake Taihu were obtained using PZDGT coupled with laser ablation ICP–MS measurement, and the apparent diffusion fluxes across the interfaces were calculated using a numerical model.

Estrategias pedagógicas basadas en el diseño universal para el aprendizaje: una aproximación desde la comunicación educativa

Libro que presenta estrategias pedagógicas para la educación inclusiva en las diferentes etapas educativas como preescolar, básica, media y universitaria.

On the Faria's inequality for the Laplacian and signless Laplacian spectra: a unified approach

Let p(G)p(G) and q(G)q(G) be the number of pendant vertices and quasi-pendant vertices of a simple undirected graph G, respectively. Let m_L±(G)(1) be the multiplicity of 1 as eigenvalue of a matrix which can be either the Laplacian or the signless Laplacian of a graph G. A result due to I. Faria states that mL±(G)(1) is bounded below by p(G)−q(G). Let r(G) be the number of internal vertices of G. If r(G)=q(G), following a unified approach we prove that mL±(G)(1)=p(G)−q(G). If r(G)>q(G) then we determine the equality mL±(G)(1)=p(G)−q(G)+mN±(1), where mN±(1) denotes the multiplicity of 1 as eigenvalue of a matrix N±. This matrix is obtained from either the Laplacian or signless Laplacian matrix of the subgraph induced by the internal vertices which are non-quasi-pendant vertices. Furthermore, conditions for 1 to be an eigenvalue of a principal submatrix are deduced and applied to some families of graphs.

The Fenix II Study: A longitudinal study of psychopathology among burn patients

Psychological symptoms are common among burn survivors. However, knowledge about epidemiology and predictors of psychopathology has shown great heterogeneity in this population. The Fenix-II Project was the first epidemiological study on the psychopathological consequences of burn injuries developed in Spain, providing a detailed analysis of the progression of psychological symptoms during the first six months after injury. Three hundred and thirty-three patients were monitored and 183 were included in this study. Posttraumatic, depression and anxiety symptoms showed a general decreasing tendency across time. At 6 months, 34 patients showed clinically significant Posttraumatic Stress Disorder (PTSD) symptoms (20.5% of 166 patients reached at 6 months) as measured with the MINI Neuropsychiatric Interview. Within this group of patients, anxiety, depression and hyperarousal increased at 30 days, and avoidance 90 days after injury. The most accurate predictors of PTSD were found to be being burned in a Motor Vehicle Accident, risk of social exclusion, low body-image adjustment, anterior trunk location of the burn injury and life threat perception during the burn-shock period. Considering these factors, clinicians may identify patients at risk of PTSD development, allowing an adequate follow up and preventive interventions which may minimize the psychological consequences of burn injuries.

Latinidade e cidadania: apontamentos sobre modelos sociais animais na poesia, da antiguidade ao iluminismo

No livro IV das Geórgicas, afamado poema didáctico de Virgílio, é descrita a vida das abelhas, apontadas como modelo de organização social e destacando-se a sua dedicação ao bem comum. O tópico tornou-se num dos paradigmas literários da Antiguidade, tendo sido repetidamente retomado, por exemplo nas obras de poetas didácticos modernos, quer europeus, quer do Novo Mundo. Referimo-nos especificamente ao poema Praedium rusticum (Toulose, 1730), do escritor inaciano francês Jacques Vanière, que aborda a sociedade das abelhas (Apes) no livro XIV, e a Rusticatio mexicana (Modena, 1781; Bolonha, 1782), do jesuíta guatemalteco Rafael Landívar, cujo livro VI descreve a sociedade dos castores (Fibri), procurando emular a obra Vanière. Na sociedade colectiva de Vanière não existe riqueza privada e cada abelha se dedica à tarefa que prefere. Em vez da ganância e do ódio prevalecem a generosidade e o amor. Na res publica dos castores, por seu lado, tal como a apresenta Landívar, existe divisão das tarefas a desempenhar e um forte sentido de comunidade. Os castores são felizes no seu trabalho, altamente inteligentes, nobres, amantes da paz e igualmente libertos de sentimentos como o ódio, a vingança e outras preocupações mais profundas. Esta comunicação pretende avaliar o modo como são apresentadas nestes textos concepções políticas e sociais que, embora procurem adaptar e integrar os ideais do Iluminismo, seguem na esteira do modelo literário virgiliano.

Changing patterns of first injection across key periods of the French Harm Reduction Policy: PrimInject, a cross sectional analysis

Background: Monitoring of emerging modes of drug consumption in France has identified new patterns of injection among youths with diverse social backgrounds, which may explain the persistence of high rates of hepatitis C virus infection. The circumstances surrounding the first injection have been poorly documented in the group of heavy drug users and in the context of the French opioid substitution treatment (OST) policy that provides expanded access to high-dosage buprenorphine (BHD). Methods: An Internet survey (Priminject) was conducted from October 2010 to March 2011 with French drug users. Four time periods were compared based on critical dates throughout the implementation of the Harm Reduction Policy in France. Results: Compared with drug users who injected for the first time prior to 1995, the aspects of drug use for users who recently injected for the first time were as follows: (1) experimentation with miscellaneous drugs before the first injection; (2) an older age at the time of first injection; (3) heroin as the drug of choice for an individual’s first injection, notwithstanding the increased usage of stimulant drugs; (4) BHD did not appear to be a pathway to injection; and (5) an increased number of users who injected their first time alone, without the help or presence of another individual. Conclusion: The PrimInject study showed that there is a group of injection drug users that is larger than the group of injection drug users observed in previous studies; therefore, it is necessary to diversify programs to reach the entire spectrum of high-risk users.

Caractérisation de nouveaux aspects de l’ataxie spastique autosomale récessive de Charlevoix-Saguenay à l’aide d’un procédé d’imagerie: la tomographie par cohérence optique (OCT)

L’Ataxie spastique autosomale récessive de Charlevoix-Saguenay (ARSACS) est un syndrome héréditaire précoce caractérisé par un tableau clinique particulier incluant des anomalies oculaires. Quatorze ARSACS et 36 témoins sains ont été suivis prospectivement durant 20 mois et ont subi différents tests neuro-ophtalmologiques et des mesures par tomographie par cohérence optique. Des augmentations de l’épaisseur moyenne de la couche de fibres nerveuses (mRNFL), de l’épaisseur fovéolaire centrale et de l’épaisseur moyenne du cube maculaire (CAT) ont été mises en évidence chez les ARSACS en comparaison avec les témoins (p<0,0001 à toutes les séances). Une différence cliniquement significative a été observée dans l’évolution au cours du suivi des épaisseurs de la mRNFL et la CAT des ARSACS par rapport aux contrôles (p=0,030, p=0,026 respectivement), et ces paramètres étaient inversement corrélés avec le degré de sévérité de la maladie, suggérant une diminution d’épaisseur de la mRNFL et de la CAT à mesure que progresse la maladie.

Exercise training reduces fatty acid availability and improves the insulin sensitivity of glucose metabolism

Aims/hypothesis - It is not known whether the beneficial effects of exercise training on insulin sensitivity are due to changes in hepatic and peripheral insulin sensitivity or whether the changes in insulin sensitivity can be explained by adaptive changes in fatty acid metabolism, changes in visceral fat or changes in liver and muscle triacylglycerol content. We investigated the effects of 6 weeks of supervised exercise in sedentary men on these variables. Subjects and methods - We randomised 17 sedentary overweight male subjects (age 50 ± 2.6 years, BMI 27.6 ± 0.5 kg/m2) to a 6-week exercise programme (n = 10) or control group (n = 7). The insulin sensitivity of palmitic acid production rate (Ra), glycerol Ra, endogenous glucose Ra (EGP), glucose uptake and glucose metabolic clearance rate were measured at 0 and 6 weeks with a two-step hyperinsulinaemic–euglycaemic clamp [step 1, 0.3 (low dose); step 2, 1.5 (high dose) mU kg−1 min−1]. In the exercise group subjects were studied >72 h after the last training session. Liver and skeletal muscle triacylglycerol content was measured by magnetic resonance spectroscopy and visceral adipose tissue by cross-sectional computer tomography scanning. Results - After 6 weeks, fasting glycerol, palmitic acid Ra (p = 0.003, p = 0.042) and NEFA concentration (p = 0.005) were decreased in the exercise group with no change in the control group. The effects of low-dose insulin on EGP and of high-dose insulin on glucose uptake and metabolic clearance rate were enhanced in the exercise group but not in the control group (p = 0.026; p = 0.007 and p = 0.04). There was no change in muscle triacylglycerol and liver fat in either group. Conclusions/interpretation - Decreased availability of circulating NEFA may contribute to the observed improvement in the insulin sensitivity of EGP and glucose uptake following 6 weeks of moderate exercise.

Reliability of nasal auscultation and their relation to middle ear condition – a clinical interest to pediatrics respiratory physiotherapy

Background: Acute respiratory infections are usual in children under three years old occurring in upper respiratory tract, having an impact on child and caregiver’s quality of life predisposing to otitis media or bronchiolitis. There are few valid and reliable measures to determine the child’s respiratory condition and to guide the physiotherapy intervention. Aim: To assess the intra and inter rater reliability of nasal auscultation, to analyze the relation between sounds’ classification and middle ear’s pressure and compliance as well as with the Clinical Severity Score. Methods: A cross-sectional observational study was composed by 125 nursery children aged up to three years old. Tympanometry, pulmonary and nasal auscultation and application of Clinical Severity Score were performed to each child. Nasal auscultation sounds’ were recorded and sent to 3 blinded experts, that classified, as “obstructed” and “unobstructed”, with a 48 hours interval, in order to analyze inter and intra rater reliability. Results: Nasal auscultation revealed a substantial inter and intra rater reliability (=0,749 and evaluator A - K= 0,691; evaluator B - K= 0,605 and evaluator C - K= 0,724, respectively). Both ears’ pressure was significantly lower in children with an "unobstructed" nasal sound when compared with an “obstructed” nasal sound (t=-3,599, p<0,001 in left ear; t=-2,258, p=0,026 in right ear). Compliance in both ears was significantly lower in children with an "obstructed" nasal sound when compared with “unobstructed” nasal sound (t=-2,728, p=0,007 in left ear; t=-3,830, p<0,001 in right ear). There was a statistically significant association between sounds’ classification and tympanograms types in both ear’s (=11,437, p=0,003 in left ear; =13,535, p=0,001 in right ear). There was a trend to children with an "unobstructed" nasal sound that had a lower clinical severity score when compared with “obstructed” children. Conclusion: It was observed a good intra and substantial inter reliability for nasal auscultation. Nasal auscultation sounds’ classification was related to middle ears’ pressure and compliance.