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Introduction: Asthma is the result of a complex interaction between genetic, environmental and socioeconomic factors. It represents a serious global public health problem. The goal of this study was to identify geographic areas for priority actions in order to control of asthma in children., Method: Ecological study that space-time statistic Scan was used. Non-elective, short-stay (type 1) paid authorizations of hospitalizations were selected according to hospitalizations year and children place of residence., Results: In the two periods of the study, the high risk primary cluster was located in the region of Barra do Bugres (relative risk = 8.17, in the first period, and 10.37, in the second). The number of high-risk clusters increased from 8, in the period 2001-2004, to 9, in 2005-2012; while low-risk clusters decreased from 6, in the initial period, to 4, in the latest. The priority geographic areas for attention and intervention for children with asthma are the region around Barra do Bugres, which remained in the two periods with high risk primary clusters and the southwest border of the State that presented increase of the risk. Furthermore, there was an increase of 87% in the number of high risk counties and a reduction of 28% of the counties of protection., Conclusion: In conclusion, the surroundings areas of Barra do Bugres and Porto Estrela and the east and northeast border of the state are priority for health care, once there was an increased risk of hospitalization of children due to asthma.

Context: The lack of thorough knowledge regarding morphological and anatomical variations of the root canal system can result in failure to identify all root canals and lead to inadequate instrumentation and consequent failure of the endodontic treatment., Aims: The aim of the study was to evaluate the anatomy of single-rooted mandibular canines using micro-computed tomography (micro-CT)., Subjects and Methods: Eighty mandibular canines were scanned by micro-CT to determine anatomic parameters: Vertucci's classification, number of lateral canals, roundness, and minor and major diameters. The shape of root canal orifices, volume, surface area, and convexity structure model index (SMI) were also evaluated., Analysis Used: The CTAn and CTvol software were used to three-dimensional and morphometric analysis., Results: All canals were classified as Vertucci Type I. Lateral canals were verified in 42.4% of the roots, in apical third. The canal diameters were decreased near the apex. The cross sections at the cementoenamel junction and 1 mm from the apex were oval in 38.3% and 79.4% of the canals, respectively. The mean canal volumes and surface areas were 11.48 ± 4.41 mm 3 ≥ and 67.29 ± 19.18 mm 2 , respectively. The SMI values indicated that mandibular canine was approximately rod like., Conclusions: The morphology of the root canal of single-rooted canines varied widely at different root levels., Competing Interests: There are no conflicts of interest.

This ecological study used data accumulated between 2001 and 2012 hospital admissions of children under five years of age with asthma in 141 municipalities in the Mato Grosso. Hospital data were extracted from the SIH/SUS system, and hospitalisation rates were estimated using the Bayesian inference method. SaTScan software was used for the calculation of the relative risk (RR). Differences in socioeconomic characteristics among municipalities with high and low hospitalization rates were evaluated by nonparametric Wilcoxon-Mann-Whitney test. This test indicates that municipalities with better socioeconomic characteristics have lower hospitalization rates. The analysis of the linear models in the two study periods indicated that the decreasing trend in the number of admissions was 3-fold higher in the 2005-2012 period compared with the 2001-2004 period. In addition, a decrease of 76% in the hospitalisation incidence rate was observed during the 12-year study period; this decrease was more evident from 2005 onward. The municipalities identified as having increased risk of hospitalisation of children with asthma were located in areas subjected to intense burning practices and with low municipal development indices.

We evaluated health-related quality of life (QoL) in HIV infection participants with virologic failure (VF) on first-line antiretroviral therapy (ART) in 9 resource-limited settings (RLS). ACTG SF-21 was completed by 512 participants at A5273 study entry; 8 domains assessed: general health perceptions (GHP), physical functioning (PF), role functioning (RF), social functioning (SF), cognitive functioning (CF), pain (P), mental health (MH), and energy/fatigue (E/F); each was scored between 0 (worst) to 100 (best). Mean QoL scores ranged from 67 (GHP) to 91 (PF, SF, CF). QoL varied by country; high VL and low CD4 were associated with worse QoL in most domains, except RF (VL only), SF (CD4 only) and CF (neither). Number of comorbidities, BMI and history of AIDS were associated with some domains. Relationships between QoL and VL varied among countries for all domains. The association of worse disease status with worse QoL may reflect low QoL when ART was initiated and/or deterioration associated with VF.

Objective: We evaluated improvement of quality of life (QoL) after 1 year of second-line antiretroviral therapy (ART) use in resource-limited settings (RLS) among adult men and women, comparing two randomized treatment arms., Design: The AIDS Clinical Trial Group A5273 was a randomized clinical trial of second-line ART comparing lopinavir/ritonavir (LPV/r) + raltegravir with LPV/r + nucleos(t)ide reverse transcriptase inhibitors (NRTIs) in participants failing a non-NRTI-containing regimen at 15 sites in nine RLS. Participants completed the AIDS Clinical Trial Group short-form-21 which has eight QoL domains with a standard score ranging from 0 (worst) to 100 (best)., Methods: Differences in QoL by randomized arm, as well as by demographic and clinical variables, were evaluated by regression models for baseline and week 48 QoL scores fitted using the generalized estimating equations method., Results: A total of 512 individuals (49% men, median age 39 years) were included. A total of 512 and 492 participants had QoL assessments at baseline and week 48, respectively. QoL improved significantly from baseline to week 48 (P < 0.001 for all domains). There was no significant difference between treatment arms for any domain. Individuals with higher viral load and lower CD4 cell count at baseline had lower mean QoL at baseline but larger improvements such that mean QoL was similar at week 48., Conclusion: Improvements in QoL were similar after starting second-line ART of LPV/r combined with either raltegravir or NRTIs in RLS. QoL scores at baseline were lower among participants with worse disease status prior to starting second-line, but after 1 year similar QoL scores were achieved.

Introduction: In recent years, Italy has seen a reduction in workplace accidents due to several factors, including the controls carried out by the Health and Safety at Work Services (PSAL) of the Local Health Units (ATS)., Objective: To verify the contribution of PSAL Services to injury reduction. In particular, to identify the existence of a difference between incidence rates of accidents in companies before and after inspections and possible variations in rates between inspected and non-inspected companies., Methods: We analyzed data of the activities carried out by the PSAL Services of the Lombardy Region in the system I.M.Pre.S@ (Computerization and Health Prevention Monitoring) in the period 2010-2015, together with data from the Regional Accident Database of the National Institute for Insurance against Accidents at Work (INAIL). The "difference in difference" (DID) method was used to evaluate the different effect on inspected and non-inspected industries., Results: Between the pre- and post-vigilance periods, inspected companies showed a greater reduction either of total injury rates (DID=-2.7 per 1000 worker-years; 90% confidence interval (CI): -4.1; -1.3) or of severe injury rates (DID=-1.1; 90% CI: -1.7; -0.5). These effects were visible in the majority of ATS and occupational sectors., Conclusions: This study, made possible by a valid and efficient regional data tracking system, has shown the positive effect of the PSAL prevention actions on the frequency of both total and severe injuries.

Purpose: To evaluate the efficacy and tolerance of a new matrix-regenerating agent (RGTA), Cacicol ® , a polymer that mimics heparan sulfates bound to extracellular matrix proteins, avoiding its proteolysis, to treat neurotrophic keratopathy (NK)., Methods: Uncontrolled prospective clinical study performed between January 2014 and May 2016. Twenty-five patients (25 eyes) with corneal neurotrophic ulcers, nonresponsive to at least 2 weeks of conservative therapy, were treated with Cacicol, instilled once/twice a week. During follow-up, slit-lamp examination, anterior segment photography, fluorescein-dye testing, and best-corrected visual acuity were analyzed. Ulcer evolution was evaluated using image analysis software (ImageJ ® ) and healing defined as decrease of the corneal ulcer area. An independent observer measured ulcer area., Results: All patients had complete corneal healing within an average of 4.13 ± 2.32 weeks. Mean ulcer area decreased significantly (P = 0.001) from 16.51% ± 18.56% (1st day) to 8.68% ± 11.25% at the 7th day and to 4.73% ± 10.75% at the 14th day. Compared with day 1, mean ulcer area decreased 60.24% after 7 days (P = 0.001), 54.92% after 14 days (P = 0.059), and 83.00% after 21 days (P = 0.003). Two cases of recurrence (8.0%) were registered. No systemic or local side effects were noticed., Conclusions: The new regenerating agent, Cacicol, represents an effective and safe therapy to treat NK.

Purpose: To evaluate the use of functional magnetic resonance imaging (MRI) to assess neuroadaptation to multifocal intraocular lenses (IOLs)., Setting: Faculty of Medicine, University of Coimbra, Coimbra, Portugal., Design: Prospective case study., Methods: Patients with bilateral diffractive IOL implantation after cataract surgery had functional MRI at postoperative intervals of 3 weeks and 6 months. A nonintervention control group was included as proof of concept. Functional stimuli consisted of sinusoidal gratings with threshold contrast and a light source to induce disability glare. Subjective quality of vision and reading performance were assessed and wavefront analyses were performed., Results: The study comprised 30 patients in the study group and 15 in the control group. Glare decreased the functional MRI signal measured for sinusoidal gratings initially (3 weeks) but not at 6 months (P = .04), which was confirmed by contrast detection under glare improvement (P = .002). Patients showed increased activity of cortical areas involved in visual attention, procedural learning, effortful cognitive control, and goal-oriented behavior in the early postoperative period, which normalized at 6 months. There were no differences in aberrations, Strehl ratio, or modulation transfer function despite significant decreases in questionnaire symptom scores and visual acuity and reading performance improvements. The control group remained unchanged., Conclusions: Neuroadaptation to multifocal IOLs took place initially through recruitment of visual attentional and procedural learning networks. Thereafter, a form of long-term adaptation/functional plasticity occurred, leading to brain activity regularization toward a non-effort pattern. These findings, which reinforce the crucial role of higher-level brain regions in the perceptual construction of vision, were consistent with functional and questionnaire outcomes and were unrelated to optical properties., (Copyright © 2017 ASCRS and ESCRS. All rights reserved.)

Purpose: To investigate the association between dysphotopsia and neural responses in visual and higher-level cortical regions in patients who recently received multifocal intraocular lens (IOL) implants., Design: Cross-sectional study., Participants: Thirty patients 3 to 4 weeks after bilateral cataract surgery with diffractive IOL implantation and 15 age- and gender-matched control subjects., Methods: Functional magnetic resonance imaging (fMRI) was performed when participants viewed low-contrast grating stimuli. A light source surrounded the stimuli in half of the runs to induce disability glare. Visual acuity, wavefront analysis, Quality of Vision (QoV) questionnaire, and psychophysical assessment were performed., Main Outcome Measures: Cortical activity (blood oxygen level dependent [BOLD] signal) in the primary visual cortex and in higher-level brain areas, including the attention network., Results: When viewing low-contrast stimuli under glare, patients showed significant activation of the effort-related attention network in the early postoperative period, involving the frontal, middle frontal, parietal frontal, and postcentral gyrus (multisubject random-effects general linear model (GLM), P < 0.03). In contrast, controls showed only relative deactivation (due to lower visibility) of visual areas (occipital lobe and middle occipital gyrus, P < 0.03). Patients also had relatively stronger recruitment of cortical areas involved in learning (anterior cingulate gyrus), task planning, and solving (caudate body). Patients reporting greater symptoms induced by dysphotic symptoms showed significantly increased activity in several regions in frontoparietal circuits, as well as cingulate gyrus and caudate nucleus (q < 0.05). We found no correlation between QoV questionnaire scores and optical properties (total and higher order aberration, modulation transfer function, and Strehl ratio)., Conclusions: This study shows the association between patient-reported subjective difficulties and fMRI outcomes, independent of optical parameters and psychophysical performance. The increased activity of cortical areas dedicated to attention (frontoparietal circuits), to learning and cognitive control (cingulate), and to task goals (caudate) likely represents the beginning of the neuroadaptation process to multifocal IOLs., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Breast cancer epithelial cells with the CD44 + /CD24 -/low phenotype possess tumor-initiating cells and epithelial-mesenchymal transition (EMT) capacity. Massive parallel sequencing can be an interesting approach to deepen the molecular characterization of these cells. We characterized CD44 + /CD24 - /cytokeratin(Ck) + /CD45 - cells isolated through flow cytometry from 43 biopsy and 6 mastectomy samples harboring different benign and malignant breast lesions. The Ion Torrent Ampliseq Cancer Hotspot panel v2 (CHPv2) was used for the identification of somatic mutations in the DNA extracted from isolated CD44 + /CD24 - /Ck + /CD45 - cells. E-Cadherin and vimentin immunohistochemistry was performed on sections from the corresponding formalin-fixed, paraffin-embedded (FFPE) blocks. The percentage of CD44 + /CD24 - /Ck + /CD45 - cells increased significantly from non-malignant to malignant lesions and in association with a significant increase in the expression of vimentin. Non-malignant lesions harbored only a single-nucleotide polymorphism (SNP). Mutations in the tumor suppressor p53 (TP53), NOTCH homolog 1 (NOTCH1), phosphatase and tensin homolog (PTEN), and v-akt murine thymoma viral oncogene homolog 1 (AKT1) genes were found in isolated CD44 + /CD24 - /Ck + /CD45 - cells from ductal carcinomas in situ (DCIS). Additional mutations in the colony-stimulating factor 1 receptor (CSF1R), ret proto-oncogene (RET), and TP53 genes were also identified in invasive ductal carcinomas (IDCs). The use of massive parallel sequencing technology for this type of application revealed to be extremely effective even when using small amounts of DNA extracted from a low number of cells. Additional studies are now required using larger cohorts to design an appropriate mutational profile for this phenotype.

Chronic nonhealing venous leg ulcers (VLUs) are widespread and debilitating, with high morbidity and associated costs; about $15 billion is spent annually on the care of VLUs in the United States. Despite this, there is a paucity of treatments for VLUs because of the lack of pathophysiologic insight into ulcer development as well as the lack of knowledge regarding biologic actions of existing VLU-targeted therapies. The bioengineered bilayered living cellular construct (BLCC) skin substitute is a U.S. Food and Drug Administration-approved biologic treatment for healing VLUs. To elucidate the mechanisms through which the BLCC promotes healing of chronic VLUs, we conducted a clinical trial (NCT01327937) in which patients with nonhealing VLUs were treated with either standard of care (compression therapy) or the BLCC together with standard of care. Tissue was collected from the VLU edge before and 1 week after treatment, and the samples underwent comprehensive microarray mRNA and protein analyses. Ulcers treated with the BLCC skin substitute displayed three distinct transcriptomic patterns, suggesting that BLCC induced a shift from a nonhealing to a healing tissue response, involving modulation of inflammatory and growth factor signaling, keratinocyte activation, and attenuation of Wnt/β-catenin signaling. In these ways, BLCC application orchestrated a shift from the chronic nonhealing ulcer microenvironment to a distinctive healing milieu resembling that of an acute, healing wound. Our findings provide in vivo evidence in VLU patients of pathways that can be targeted in the design of new therapies to promote healing of chronic VLUs., (Copyright © 2017, American Association for the Advancement of Science.)

Gene therapy has long been heralded as the new hope to evolve from symptomatic care of genetic pathologies to a full cure. Recent successes in using gene therapy for treating several ocular and haematopoietic pathologies have shown the great potential of this approach that, in the early days, relied on the use of viral vectors, which were considered by many to be undesirable for human treatment. Therefore, there is considerable interest and effort in developing non-viral vectors, with efficiency close to that of viral vectors. The aim of this study was to develop suitable non-viral carriers for gene therapy to treat pathologies affecting the retina. In this study poly(2-(N,N-dimethylamino)ethyl methacrylate), PDMAEMA was synthesized by reversible addition-fragmentation chain transfer (RAFT) and the in vitro cytocompatibility and transfection efficiency of a range of polymer:DNA ratios evaluated using a retinal cell line; in vivo biocompatibility was evaluated by ocular injection in C57BL/6 mice. The results showed that through RAFT, it is possible to produce a defined-size polymer that is compatible with cell viability in vitro and capable of efficiently directing gene expression in a polymer-DNA ratio-dependent manner. When injected into the eyes of mice, these vectors induced a transient, mild inflammation, characteristic of the implantation of medical devices. These results form the basis of future studies where RAFT-synthesized PDMAEMA will be used to deliver gene expression systems to the retina of mouse models of retinal pathologies. Copyright © 2014 John Wiley & Sons, Ltd., (Copyright © 2014 John Wiley & Sons, Ltd.)

Conventionally, embryonic stem cells (ESCs) are cultured on gelatin or over a mitotically inactivated monolayer of mouse embryonic fibroblasts (MEFsi). Considering the lack of versatile, non-animal-derived and inexpensive materials for that purpose, we aimed to find a biomaterial able to support ESC growth in a pluripotent state that avoids the need for laborious and time-consuming MEFsi culture in parallel with mouse ESC (mESC) culture. Undifferentiated mESCs were cultured in a new nanofibre material designed for ESC culture, which is based on the self-assembly of a triblock co-polymer, poly(ethyleneglycol-β-trimethylsilyl methacrylate-β-methacrylic acid), conjugated with the peptide glycine-arginine-glycine-aspartate-serine, to evaluate its potential application in ESC research. The morphology, proliferation, viability, pluripotency and differentiation potential of mESCs were assessed. Compared to conventional stem cell culture methodologies, the nanofibres promoted a higher increase in mESCs number, enhanced pluripotency and were able to support differentiation after long-term culture. This newly developed synthetic system allows the elimination of animal-derived matrices and provides an economic method of ESC culture, made of a complex network of nanofibres in a scale similar to native extracellular matrices, where the functional properties of the cells can be observed and manipulated. Copyright © 2013 John Wiley & Sons, Ltd., (Copyright © 2013 John Wiley & Sons, Ltd.)

Biofilm bacteria are more resistant to antibiotics than planktonic cells. Propolis possesses antimicrobial activity. Generally, nanoparticles containing heavy metals possess antimicrobial and antibiofilm properties. In this study, the ability of adherence of Methicillin Resistant Strains of Staphylococcus aureus (MRSA) to catheters treated with magnetite nanoparticles (MNPs), produced by three methods and functionalized with oleic acid and a hydro-alcoholic extract of propolis from Morocco, was evaluated. The chemical composition of propolis was established by gas chromatography mass spectrometry (GC-MS), and the fabricated nanostructures characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Mossbauer spectroscopy and Fourrier transform infrared spectroscopy (FTIR). The capacity for impairing biofilm formation was dependent on the strain, as well as on the mode of production of MNPs. The co-precipitation method of MNPs fabrication using Fe(3+) and Na₂SO₃ solution and functionalized with oleic acid and propolis was the most effective in the impairment of adherence of all MRSA strains to catheters (p < 0.001). The adherence of the strain MRSA16 was also significantly lower (p < 0.001) when the catheters were treated with the hybrid MNPs with oleic acid produced by a hydrothermal method. The anti-MRSA observed can be attributed to the presence of benzyl caffeate, pinocembrin, galangin, and isocupressic acid in propolis extract, along with MNPs. However, for MRSA16, the impairment of its adherence on catheters may only be attributed to the hybrid MNPs with oleic acid, since very small amount, if any at all of propolis compounds were added to the MNPs.

Purpose: To develop 27 short sentence optotypes for the Portuguese version of the Radner Reading Charts., Methods: Thirty-four Portuguese sentences were constructed following the concept of the Radner Reading Charts to obtain highly comparable sentences in terms of lexical difficulty, syntactical complexity, word length, number of syllables, and position of words. A long text (106 words) at the 5th grade reading level was also tested to assess the validity of the reading speeds obtained with the short sentences. The short sentences and long text were tested in 50 volunteers with similar educational backgrounds (mean age 30.98 years ± 6.99 years, range 19-47 years). Reading speeds were measured with a stop-watch and reported as words per minute (wpm). The reading time for each of the short sentences to be selected for the chart was defined as falling within the range of the mean ± 0.40 × standard deviation (SD)., Results: The overall mean reading speed for each of the short sentences was 235.43 ± 36.39 wpm. The 27 sentences with a mean between 220.8 and 250.0 wpm (overall mean ± 0.40 × SD) were selected for construction of the reading charts. The mean reading speed for the long text was 212.42 ± 26.20 wpm. Correlation between the selected short sentences and long text was high (r =0.86). Reliability analysis yielded an overall Cronbach's alpha coefficient of 0.97., Conclusions: The 27 short Portuguese sentences were highly comparable in terms of syntactical structure, number, position and length of words, lexical difficulty, and reading length. This reading test can overcome the limitations of the current tests for homogeneity and comparability, reducing subjectivity in the evaluation of the functional outcomes of medical and surgical ophthalmologic treatments.

Background: For second-line antiretroviral therapy, WHO recommends a boosted protease inhibitor plus nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs). However, concerns about toxicity and cross-resistance motivated a search for regimens that do not contain NRTIs. We aimed to assess whether boosted lopinavir plus raltegravir would be non-inferior to boosted lopinavir plus NRTIs for virological suppression in resource-limited settings., Methods: A5273 was a randomised, open-label, phase 3, non-inferiority study at 15 AIDS Clinical Trials Group (ACTG) research sites in nine resource-limited countries (three sites each in India and South Africa, two each in Malawi and Peru, and one each in Brazil, Kenya, Tanzania, Thailand, and Zimbabwe). Adults with plasma HIV-1 RNA concentrations of at least 1000 copies per mL after at least 24 weeks on a regimen based on a non-NRTI inhibitor were randomly assigned (1:1) to receive oral ritonavir-boosted lopinavir (100 mg ritonavir, 400 mg lopinavir) plus 400 mg raltegravir twice a day (raltegravir group) or to ritonavir-boosted lopinavir plus two or three NRTIs selected from an algorithm (eg, zidovudine after failure with tenofovir and vice versa; NRTI group). Randomised group assignment was done with a computer algorithm concealed to site personnel, and stratified by HIV-1 RNA viral load, CD4 cell count, and intention to use zidovudine, with the groups balanced by each site. The primary endpoint was time to confirmed virological failure (two measurements of HIV-1 RNA viral load >400 copies per mL) at or after week 24 in the intention-to-treat population. Non-inferiority (10% margin) was assessed by comparing the cumulative probability of virological failure by 48 weeks. This trial was registered with ClinicalTrials.gov, NCT01352715., Findings: Between March 13, 2012, and Oct 2, 2013, we randomly assigned 515 participants: 260 to the raltegravir group and 255 to the NRTI group; two participants in the raltegravir group and one in the NRTI group were excluded from analyses because of ineligibility. By the end of follow-up (October, 2014), 96 participants had virological failure (46 in the raltegravir group and 50 in the NRTI group). By 48 weeks, the cumulative probability of virological failure was 10·3% (95% CI 6·5-14·0) in the raltegravir group and 12·4% (8·3-16·5) in the NRTI group, with a weighted difference of -3·4% (-8·4 to 1·5), indicating that raltegravir was non-inferior, but not superior, to NRTIs. 62 (24%) participants in the raltegravir group and 81 (32%) in the NRTI group had grade 3 or higher adverse events; 19 (7%) and 29 (11%), respectively, had serious adverse events. Three participants in each group died, all from HIV-related causes., Interpretation: In settings with extensive NRTI resistance but no available resistance testing, our data support WHO's recommendation for ritonavir-boosted lopinavir plus NRTI for second-line antiretroviral therapy. Ritonavir-boosted lopinavir plus raltegravir is an appropriate alternative, especially if NRTI use is limited by toxicity., Funding: National Institutes of Health., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: To analyze the efficacy and safety of topography-guided photorefractive keratectomy (TG-PRK) to treat irregular astigmatism after corneal transplantation., Methods: This was a retrospective observational case series. Eyes with irregular astigmatism after penetrating keratoplasty treated with TG-PRK (Allegretto Wave Eye-Q) with the topography-guided customized ablation treatment protocol were included. All treatments had been planned to correct the topographic irregularities, as well as to reduce the refractive error after neutralizing the induced refractive change. Clinical records, treatment plan, and the examinations performed were reviewed and the following data were collected: corrected and uncorrected distance visual acuities; manifest refraction; topographic parameters, and corneal endothelial cell count., Results: We included 31 eyes [30 patients; mean age 45.0 ± 13.4 (SD) years]. At the last postoperative follow-up (mean 9.2 ± 8.2 months), we observed a significant improvement in corrected (P = 0.001) and uncorrected distance visual acuities (P < 0.001). There was a gain of ≥1 uncorrected distance visual acuity line in 96.8% (n = 30) of the eyes. Similarly, the refractive parameters also improved (cylinder P < 0.001; spherical equivalent P = 0.002). At the last visit, 54.8% (n = 17) of the patients presented a spherical equivalent of ±1 D. The 3-mm topographic irregularity also decreased significantly (P < 0.001). There was no significant variation of the corneal endothelial cell count., Conclusions: This is the largest case series of TG-PRK to treat irregular astigmatism in postcorneal transplantation eyes. Our results confirm that TG-PRK is an efficient treatment, associated with significant improvements of both visual acuity and refractive parameters.

Purpose: A successful gene therapy approach can prevent or treat congenital and acquired diseases. However, there is still no ideal non-viral vector for gene delivery in a safe and timely manner. In this report the anionic polymer hyaluronic acid (HA) was investigated as a potential vector for gene therapy. Due to its intrinsic characteristics it constitutes an excellent candidate to deliver therapeutic genes, pending the modification of its surface charge., Methods: To modify its charge, HA was modified with cystamine. Several formulations were prepared using modified HA combined with sodium sulfate, sodium triphosphate, K-carrageenan and chitosan. Vectors were characterized with respect to size, charge, DNA load and its protection, and effect on cell viability. The better performing formulations were further evaluated in vitro for their transfection efficiency in HEK293T and ARPE-19 cells., Results: Cell viability assays showed low cytotoxicity for both polymers. Gene transfer efficiency depended on cell line and formulation, but no increased transfection efficiency was observed with the modified polymer., Conclusions: HA has great potential as a gene therapy vector, but further optimization, including incorporation of a higher percentage of positive groups in HA, is needed before its use as a gene delivery vector., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: To quantitatively evaluate visual function 12 months after bilateral implantation of the Physiol FineVision® trifocal intraocular lens (IOL) and to compare these results with those obtained in the first postoperative month., Methods: In this prospective case series, 20 eyes of 10 consecutive patients were included. Monocular and binocular, uncorrected and corrected visual acuities (distance, near, and intermediate) were measured. Metrovision® was used to test contrast sensitivity under static and dynamic conditions, both in photopic and low-mesopic settings. The same software was used for pupillometry and glare evaluation. Motion, achromatic, and chromatic contrast discrimination were tested using 2 innovative psychophysical tests. A complete ophthalmologic examination was performed preoperatively and at 1, 3, 6, and 12 months postoperatively. Psychophysical tests were performed 1 month after surgery and repeated 12 months postoperatively., Results: Final distance uncorrected visual acuity (VA) was 0.00 ± 0.08 and distance corrected VA was 0.00 ± 0.05 logMAR. Distance corrected near VA was 0.00 ± 0.09 and distance corrected intermediate VA was 0.00 ± 0.06 logMAR. Glare testing, pupillometry, contrast sensitivity, motion, and chromatic and achromatic contrast discrimination did not differ significantly between the first and last visit (p&gt;0.05) or when compared to an age-matched control group (p&gt;0.05)., Conclusions: The Physiol FineVision® trifocal IOL provided satisfactory full range of vision and quality of vision parameters 12 months after surgery. Visual acuity and psychophysical tests did not vary significantly between the first and last visit.

Clouston syndrome is a rare genodermatosis that affects skin and annexes. It is a form of ectodermal dysplasia characterized by generalized hypotrichosis, palmoplantar hyperkeratosis and nail dystrophy. This paper reports a 25-year follow-up of a patient with Clouston syndrome, from childhood to adulthood, monitoring diagnosis and clinical course of the disease.

Diabetes Mellitus (DM) is a chronic, severe disease rapidly increasing in incidence and prevalence and is associated with numerous complications. Patients with DM are at high risk of developing diabetic foot ulcers (DFU) that often lead to lower limb amputations, long term disability, and a shortened lifespan. Despite this, the effects of DM on human foot skin biology are largely unknown. Thus, the focus of this study was to determine whether DM changes foot skin biology predisposing it for healing impairment and development of DFU. Foot skin samples were collected from 20 patients receiving corrective foot surgery and, using a combination of multiple molecular and cellular approaches, we performed comparative analyses of non-ulcerated non-neuropathic diabetic foot skin (DFS) and healthy non-diabetic foot skin (NFS). MicroRNA (miR) profiling of laser captured epidermis and primary dermal fibroblasts from both DFS and NFS samples identified 5 miRs de-regulated in the epidermis of DFS though none reached statistical significance. MiR-31-5p and miR-31-3p were most profoundly induced. Although none were significantly regulated in diabetic fibroblasts, miR-29c-3p showed a trend of up-regulation, which was confirmed by qPCR in a prospective set of 20 skin samples. Gene expression profiling of full thickness biopsies identified 36 de-regulated genes in DFS (>2 fold-change, unadjusted p-value ≤ 0.05). Of this group, three out of seven tested genes were confirmed by qPCR: SERPINB3 was up-regulated whereas OR2A4 and LGR5 were down-regulated in DFS. However no morphological differences in histology, collagen deposition, and number of blood vessels or lymphocytes were found. No difference in proliferative capacity was observed by quantification of Ki67 positive cells in epidermis. These findings suggest DM causes only subtle changes to foot skin. Since morphology, mRNA and miR levels were not affected in a major way, additional factors, such as neuropathy, vascular complications, or duration of DM, may further compromise tissue's healing ability leading to development of DFUs.

Unpredictable pharmacokinetics (PK) in burn patients may result in plasma concentrations below concentrations that are effective against common pathogens. The present study evaluated the imipenem PK profile and pharmacokinetic/pharmacodynamics (PK/PD) correlation in burn patients. Fifty-one burn patients, 38.7 years of age (mean), 68.0 kg, 36.3% total burn surface area (TBSA), of whom 84% (43/51) exhibited thermal injury, 63% inhalation injury and 16% electrical injury (8/51), all of whom were receiving imipenem treatment were investigated. Drug plasma monitoring, PK study (120 sets of plasma levels) and PK/PD correlation were performed in a series of blood samples. Only 250 μl of plasma samples were required for drug plasma measurements using the ultra filtration technique for the purification of biological matrix and quantification using liquid chromatography. Probability of target attainment (PTA) was calculated using a PD target of 40% free drug concentrations above the minimum inhibitory concentration (40%fT>MIC). Significant differences in PK parameters (medians), such as biological half-life (2.2 vs 5.5 h), plasma clearance (16.2 vs 1.4 l h(-1)) and volume of distribution (0.86 vs 0.19 l kg(-1)), were registered in burn patients via comparisons of set periods with normal renal function against periods of renal failure. Correlations between creatinine clearance and total body plasma clearance were also obtained. In addition, the PK profile did not change according to TBSA during sets when renal function was preserved. PTA was >89% for MIC values up to 4 mg l(-1). In conclusion, imipenem efficacy for the control of hospital infection on the basis of PK/PD correlation was guaranteed for burn in patients at the recommended dose regimens for normal renal function (31.1±9.7 mg kg(-1) daily), but the daily dose must be reduced to 17.2±9.7 mg kg(-1) during renal failure to avoid neurotoxicity.

As the regional influenza reference centre operating within the Italian network InfluNet, here we report data on virological and epidemiological surveillance of influenza, as well as on the vaccination coverage rates achieved in Lombardy (Northern Italy) over 10 consecutive winter seasons (2004-2014).   Over the past 10 years, influenza vaccine coverage declined both in the general population (from 15.7% in 2004-2005 to 11.7% in 2013-2014) and in the vaccine-target population of individuals ≥65-y-of-age (from 65.3% in 2004-2005 to 48.6% in 2013-2014) and is far below the minimum planned threshold level (75%). The highest influenza-like illness (ILI) rates were recorded during the 2004-2005 and 2009-2010 epidemics (peak incidence: 12.04‰ and 13.28‰, respectively). Both seasons were characterised by the introduction of novel viral strains: A/Fujian/411/2002(H3N2) (a drifted hemagglutinin variant) and A/California/7/2009(H1N1) pandemic virus (a swine origin quadruple reassortant), respectively. Because the antigenic match between vaccine and circulating strains was good in both of these seasons, a relevant proportion of cases may have been prevented by vaccination. A different situation was observed during the 2011-2012 season, when ILI morbidity rates in individuals ≥65-y-of-age were 1.5-6-fold higher than those registered during the other epidemics under review. The higher morbidity resulted from the circulation during the 2011-2012 season of an A/Victoria/361/2011(H3N2)-like variant that presented a reduced genetic match with the A(H3N2) strain included in the 2011-2012 vaccine composition. The continuous surveillance of the characteristics of circulating viruses is an essential tool for monitoring their matching with seasonal vaccine strains. Strategies to increase coverage rates are warranted.

Purpose: This paper aims to review the morphological and functional characteristics of patients affected by familial amyloid polyneuropathy (FAP), with greater focus on type I and its progression after liver transplantation. We also analyse therapeutic options for the ophthalmic manifestations., Methods: The literature from 2002 through 2015 was reviewed, with a total of 45 articles studied, using the key terms related to amyloidosis and its therapeutic approaches. Information was collated, evaluated, critically assessed, and then summarised in its present form. PATHOPHYSIOLOGY AND TREATMENT: FAP results from mutation of the transthyretin gene, with Val30Met being the most frequent substitution. The symptoms are those typical of a sensorimotor autonomic neuropathy and can be halted with liver transplantation. Nowadays there are new medical therapies that delay the progression of the systemic neuropathy. However, there are still no options to avoid ocular disease., Conclusion: The main ocular manifestations in patients with FAP type I are amyloid deposition in the vitreous, dry eye, and secondary glaucoma. Despite liver transplantation, eye synthesis of amyloid persists and is associated with progressive ocular manifestations, which require continued ophthalmologic follow-up. New therapeutic strategies are therefore needed, particularly to target the ocular synthesis of the abnormal protein.

The recycling of platinum-group metals from wastes such as autocatalytic converters is getting growing attention due to the scarcity of these precious metals and the market pressure originated by increase of demand in current and emerging applications. Hydrometallurgical treatment of such wastes is an alternative way to the most usual pyrometallurgical processes based on smelter operations. This paper focuses on the development of a leaching process using cupric chloride as oxidising agent, in HCl media, for recovery of palladium and rhodium from a spent catalyst. The chloride media allows the adequate conditions for oxidising and solubilising the metals, as demonstrated by equilibrium calculations based on thermodynamic data. The experimental study of the leaching process revealed that Pd solubilisation is clearly easier than that of Rh. The factors temperature, time, and HCl and Cu(2+) concentrations were significant regarding Pd and Rh leaching, the latter requiring higher factor values to achieve the same results. Leaching yields of 95% Pd and 86% Rh were achieved under optimised conditions (T = 80 °C, t = 4h, [HCl] = 6M, [Cu(2+)] = 0.3M)., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Zuccagnia punctata Cav. has been used as a traditional medicine in Argentina for the treatment of bacterial and fungal infections. In this study, we evaluated the ability of Z. punctata extract (ZpE) and compounds isolated from it to inhibit the growth and virulence factors of Candida species. ZpE showed inhibitory activity against planktonic cells of all assayed Candida species with MIC values of 400 microg/mL and with MFC values between 400 and 1,200 microg/mL. The principal identified compounds by HPLC-MS/MS and UV-VIS were chalcones (2',4'-dihydroxy-3'-methoxychalcone, 2',4'- dihydroxychalcone), flavones (galangin, 3,7-dihydroxyflavone and chrysin) and flavanones (naringenin, 7-hydroxyflavanone and pinocembrine). These compounds were more effective as inhibitors than the extracts upon biofilm formation as well as on preformed Candida biofilm and yeast germ tube formation. Furthermore, ZpE and chalcones are able to inhibit exoenzymes, which are responsible for the invasion mechanisms of the pathogens. All these effects could moderate colonization, thereby suppressing the pathogen invasive potential. Our results indicate that ZpE and chalcones could be used in antifungal therapy.

To analyze photorefractive keratectomy (PRK) outcomes in myopia and myopic astigmatism correction using the WaveLight Allegretto Wave Eye-Q(®) excimer laser system (WaveLight Laser Technologie AG, Erlangen, Germany). 222 eyes of 151 patients underwent PRK (mean age 33.5 ± 6.8 years). Pre-operative best spectacle-corrected visual acuity (BSCVA) ranged from 0.4 to -0.1 logMAR (mean -0.03 ± 0.06). Mean spherical equivalent (SE) was -3.29 ± 1.20 D. Efficacy, predictability and safety were evaluated. Minimum follow-up was 3 months. Accountability at 3 and 6 months was 100 and 54 %, respectively (median follow-up 5 months, mean 5.2 ± 2.6 months). At 3 months, mean uncorrected visual acuity (UCVA) was -0.02 ± 0.07 logMAR, BSCVA -0.03 ± 0.05 logMAR, efficacy index 0.98 and safety index 1.02. UCVA was ≥20/16 in 40.1 %, ≥20/20 in 86.5 % and ≥20/25 in 98.2 %. Mean SE was -0.02 ± 0.20 D. Residual refractive error was ± 0.13 D in 81.5 %, ± 0.25 D in 88.7 % and ± 0.50 D in 97.7 %. At 6 months, outcomes were similar: mean UCVA was -0.02 ± 0.07 logMAR, BSCVA -0.03 ± 0.06 logMAR, efficacy index 1.00 and safety index 1.03. UCVA was ≥20/16 in 43.7 %, ≥20/20 in 86.6 % and ≥20/25 in 96.6 %. Mean SE was -0.02 ± 0.17 D. Residual refractive error was ± 0.13 D in 86.6 %, ± 0.25 D in 93.3 % and ± 0.50 D in 98.3 %. Refractive stability was achieved at 3 months. No patient lost more than one line of BSCVA. There were no retreatments. The WaveLight Allegretto Wave Eye-Q is effective, predictable and safe in low-to-moderate myopia and myopic astigmatism PRK correction.

Microfluidic paper-based analytical devices (μPADs) fabricated by wax-printing are suitable platforms for the development of simple and affordable molecular diagnostic assays for infectious diseases, especially in resource-limited settings. Paper devices can be modified for biological assays by adding appropriate reagents to the test areas. For this purpose, the use of affinity immobilization strategies can be a good solution for bioactive paper fabrication. This paper describes a methodology to capture labeled-DNA strands and hybrids on paper via the anchoring of antibodies with a fusion protein that combines a family 3 carbohydrate binding module (CBM) from Clostridium thermocellum, with high affinity to cellulose, and the ZZ fragment of the staphyloccocal protein A, which recognizes IgG antibodies via their Fc portion. Antibodies immobilized via CBM-ZZ were able to capture appropriately labeled (biotin, fluorescein) DNA strands and DNA hybrids. The ability of an antibody specific to biotin to discriminate complementary from noncomplementary, biotin-labeled targets was demonstrated in both spot and microchannel assays. Hybridization was detected by fluorescence emission of the fluorescein-labeled DNA probe. The efficiency of the capture of labeled-DNA by antibodies immobilized on paper via the CBM-ZZ construct was significantly higher when compared with a physical adsorption method where antibodies were simply spotted on paper without the intermediation of other molecules. The experimental proof of concept of wax-printed μPADs functionalized with CBM-ZZ for DNA detection at room temperature presented in this study constitutes an important step toward the development of easy to use and affordable molecular diagnostic tests.

Background/aim: The Cancer Stem Cell (CSC) model proposes that cancer is driven by a cellular component which possesses stem cell (SC) properties, cancer stem cells (CSCs), a distinct cell-type which is tumorigenic and capable of invasion and metastasis. Enzymatic activity of aldehyde dehydrogenase-1 (ALDH1), a de-toxifying enzyme that oxidizes intracellular aldehydes, has been used as a marker of normal and malignant breast stem cells (BSCs). CD44-transmembrane protein has already been shown to possess the ability to identify breast epithelial cells with stem properties., Materials and Methods: In order to compare two of the currently most reliable BSCs markers, ALDH1 and CD44, and to correlate their expression within different breast lesions, 190 samples from breast cancer specimens were analyzed by tissue microarrays., Results: ALDH1 expression was observed in 85.43% and CD44 in 90.3% of all samples. No overexpression was observed for ALDH1 between invasive tumors, ductal carcinomas in situ and non-malignant lesions of breast, although ALDH1 had a significant negative correlation with estrogen-receptor (ER) and progesterone-receptor (PR) status (p=0.002 and p=0.001, respectively) and a positive correlation with CD44 (p<0.001). Moreover, combined overexpression of ALDH1 and CD44 was observed in ductal in situ tumors (p<0.001)., Conclusion: The combined overexpression of these markers in ductal carcinomas in situ is in agreement with the CSC model in breast cancer.

Introduction: In some studies including small populations of patients undergoing specific surgery, an intraoperative liberal infusion of fluids was associated with increasing morbidity when compared to restrictive strategies. Therefore, to evaluate the role of excessive fluid infusion in a general population with high-risk surgery is very important. The aim of this study was to evaluate the impact of intraoperative fluid balance on the postoperative organ dysfunction, infection and mortality rate., Methods: We conducted a prospective cohort study during one year in four ICUs from three tertiary hospitals, which included patients aged 18 years or more who required postoperative ICU after undergoing major surgery. Patients who underwent palliative surgery and whose fluid balance could change in outcome were excluded. The calculation of fluid balance was based on preoperative fasting, insensible losses from surgeries and urine output minus fluid replacement intraoperatively., Results: The study included 479 patients. Mean age was 61.2 ± 17.0 years and 8.8% of patients died at the hospital during the study. The median duration of surgery was 4.0 (3.2 to 5.5) h and the value of the Simplified Acute Physiology Score (SAPS) 3 score was 41.8 ± 14.5. Comparing survivors and non-survivors, the intraoperative fluid balance from non-survivors was higher (1,950 (1,400 to 3,400) mL vs. 1,400 (1,000 to 1,600) mL, P <0.001). Patients with fluid balance above 2,000 mL intraoperatively had a longer ICU stay (4.0 (3.0 to 8.0) vs. 3.0 (2.0 to 6.0), P <0.001) and higher incidence of infectious (41.9% vs. 25.9%, P = 0.001), neurological (46.2% vs. 13.2%, P <0.001), cardiovascular (63.2% vs. 39.6%, P <0.001) and respiratory complications (34.3% vs. 11.6%, P <0.001). In multivariate analysis, the fluid balance was an independent factor for death (OR per 100 mL = 1.024; P = 0.006; 95% CI 1.007 to 1.041)., Conclusions: Patients with excessive intraoperative fluid balance have more ICU complications and higher hospital mortality.

Purpose: To compare visual function after bilateral implantation of multifocal Lentis Mplus LS-312 (Group A) or Acrysof Restor SN6AD1 (Group B) intraocular lenses (IOLs)., Setting: Ophthalmology Unit, Centro Hospitalar e Universitário de Coimbra, and Visual Neuroscience Laboratory, IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal., Design: Comparative case series., Methods: Patients between 49 years and 76 years had bilateral cataract surgery with multifocal IOL implantation. Patients were evaluated preoperatively and 3 months postoperatively for distance, intermediate, and near visual acuities; static photopic and mesopic contrast sensitivity; and visual acuity under a glare source using the Metrovision contrast sensitivity platform. Color vision was evaluated with the Cambridge Colour Test., Results: Group A comprised 56 eyes and Group B, 44 eyes. Visual and refractive results were comparable between the 2 groups. Photopic contrast sensitivity was significantly better in Group B at intermediate (2.2 cycles per degree [cpd] and 3.4 cpd) and high (7.1 cpd and 23.6 cpd) spatial frequencies. Under low mesopic conditions (0.08 candelas/m(2)), differences were significant at 1.1 cpd and 2.2 cpd spatial frequencies. There were no differences in visual acuity under a glare source or in color vision., Conclusions: Both IOLs provided good distance, intermediate, and near visual acuities. Visual acuity under a glare source and color vision were similar in the 2 groups. However, photopic and low mesopic contrast sensitivities were better in Group B, particularly for intermediate spatial frequencies, which are important for night driving., (Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Wheezing is highly prevalent in Brazil, with variations in rates and risk factors between the regions of the country. This cross-sectional study aimed to analyze the prevalence of wheezing in children under 5 years of age (n = 733) in Cuiabá, Mato Grosso State, Brazil. The study used a brief version of the standardized instrument from the International Study of Wheezing in Infants (EISL). Analysis of factors associated used logistic regression with a hierarchical approach. Prevalence of wheezing in the previous 12 months was 43.2%. Factors associated with wheezing were: lack of at least 6 months of breastfeeding (adjusted OR = 1.91; 95%CI: 1.18-3.06), diagnosis of asthma in the family (adjusted OR = 2.02; 95%CI: 1.06-3.87), current respiratory infection (adjusted OR = 1.81; 95%CI: 1.05-3.14), and male gender (adjusted OR = 1.50; 95%CI: 1.07-2.11). The study concludes that prevalence of wheezing is high among children in this age bracket in Cuiabá and is associated with factors related to allergy, current respiratory infection, and male gender.

Aim: To perform Descemet stripping automated endothelial keratoplasty (DSAEK) using a novel technique to obtain very thin (<100 µm) posterior corneal disks., Methods: Twenty five DSAEK grafts were prepared with two sequential cuts: the first cut, of variable thickness, was made with a femtosecond laser and the second with a 300 µm microkeratome head. Spectacle corrected visual acuity, endothelial cell density evaluation with specular microscopy and anterior segment optical coherence tomography to measure central and peripheral graft thickness was performed preoperatively and postoperatively at 1, 3 and 6 months., Results: There were no irregular cuts or perforations during tissue preparation. Central graft thickness was 79.6 µm (SD ± 14.5; range 54-98) and 69.3 µm (SD ± 14.2; range 49-96) at 3 and 6 months. Corrected distance visual acuity improved from 0.91 logMAR preoperatively to 0.11 logMAR at 6 months. Donor endothelial cells averaged 2675 cells/mm(2) preoperatively and 1729 cells/mm(2) at 6 months. There were no graft detachments., Conclusions: This new technique consistently yielded very thin grafts (<100 µm), excellent visual acuity results and good endothelial cell counts. No donor tissue was wasted.

The antioxidant capacity of irradiated κ-, ι-, λ-carrageenans were investigated using the hydroxyl radical scavenging assay, reducing power assay and DPPH radical scavenging capacity assay. The degree of oxidative inhibition increased with increasing concentration and dose. The type of carrageenan had also an influence on its antioxidant activity which followed the order of lambda

Purpose: To evaluate the use of a femtosecond laser combined with a microkeratome in the preparation of posterior corneal disks for Descemet stripping automated endothelial keratoplasty (DSAEK)., Methods: This experimental study involved ultrathin DSAEK tissue preparation of 22 donor corneas unsuitable for transplantation. The first cut was performed with an Intralase® FS60 laser and the second cut with a Moria CBm 300-µm microkeratome. The thickness of the first cut was modified for each cornea to obtain a final graft thickness of less than 110 µm. Precut and postcut central pachymetry were performed with an ultrasonic pachymeter. Central endothelial cell density (ECD) was calculated before and 24 hours after tissue preparation., Results: Final graft thickness was 105.0 ± 26.1 (SD) µm (range 65-117). The mean microkeratome head cut thickness was 324.5 ± 10.9 µm (range 310-345). Precut and postcut ECDs averaged 2250 ± 222 and 2093 ± 286 cells/mm2, respectively, representing 6.9% of cell loss. No corneas were perforated., Conclusion: Femtosecond FS60 lasers and Moria CBm 300-µm microkeratomes can be used sequentially to prepare consistently thin DSAEK grafts with no irregular cuts or cornea perforations.

Melanomas demonstrate chromosomal instability (CIN). In fact, CIN can be used to differentiate melanoma from benign nevi. The exact molecular mechanisms that drive CIN in melanoma have yet to be fully elucidated. Cancer/testis antigens are a unique group of germ cell proteins that are found to be primarily expressed in melanoma as compared to benign nevi. The abnormal expression of these germ cell proteins, normally expected only in the testis and ovaries, in somatic cells may lead to interference with normal cellular pathways. Germ cell proteins that may be particularly critical in CIN are meiosis proteins. Here, we review pathways unique to meiosis with a focus on how the aberrant expression of meiosis proteins in normal mitotic cells "meiomitosis" could impact chromosomal instability in melanoma and other cancers.

Chitosan/carrageenan/tripolyphosphate nanoparticles were prepared by polyelectrolyte complexation/ionic gelation, the latter compound acting as cross-linker. The incorporation of the three components in the nanoparticle matrix was assessed by analytical techniques (FTIR, XPS and TOF-SIMS). Using chitosan/carrageenan nanoparticles as control, the effect of the cross-linker in the particles properties was studied. A decrease in size (from 450-500 nm to 150-300 nm) and in zeta potential (from +75 - +85 mV to +50 - +60 mV), and an increase in production yield (from 15-20% to 25-35%), and in stability (from one week to up to 9 months) were observed. Also, a correlation between positive to negative charge ratios in the formulations and the above characteristics was established. The small size and high positive surface charge make the developed chitosan/carrageenan/tripolyphosphate nanoparticles potential tools for an application in mucosal delivery of macromolecules., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Germ cell protein expression in melanoma has been shown to correlate with malignancy, severity of disease and to serve as an immunologic target for therapy. However, very little is known about the role that germ cell proteins play in cancer development. Unique germ cell pathways include those involved in immortalization, genetic evolution, and energy metabolism. There is an ever increasing recognition that within tumors there is a subpopulation of cells with stem-cell-like characteristics that play a role in driving tumorgenesis. Stem cell and germ cell biology is intertwined. Given the enormous potential and known expression of germ cell proteins in melanoma, it is possible that they represent a largely untapped resource that may play a fundamental role in tumor development and progression. The purpose of this paper is to provide an update on the current value of germ cell protein expression in melanoma diagnosis, prognosis, and therapy, as well as to review critical germ cell pathways and discuss the potential roles these pathways may play in malignant transformation.

Context and Objective: Anemia and blood transfusions are common in intensive care. This study aimed to evaluate epidemiology and outcomes among critically ill patients under a restrictive transfusion strategy., Design and Setting: Prospective observational cohort study in an intensive care unit (ICU) at a tertiary hospital., Methods: All adults admitted to the ICU over a one-year period who remained there for more than 72 hours were included, except those with acute coronary syndrome, ischemic stroke, acute hemorrhage, prior transfusion, pregnant women and Jehovah's Witnesses. The restrictive strategy consisted of transfusion indicated when hemoglobin levels were less than or equal to 7.0 g/dl., Results: The study enrolled 167 patients; the acute physiology and chronic health evaluation II (APACHE II) score was 28.9 ± 6.5. The baseline hemoglobin level was 10.6 ± 2.2 g/dl and on day 28, it was 8.2 ± 1.3 g/dl (P < 0.001). Transfusions were administered to 35% of the patients. In the transfusion group, 61.1% did not survive, versus 48.6% in the non-transfusion group (P = 0.03). Transfusion was an independent risk factor for mortality (P = 0.011; odds ratio, OR = 2.67; 95% confidence interval, CI = 1.25 to 5.69). ICU stay and hospital stay were longer in the transfusion group: 20.0 (3.0-83.0) versus 8.0 (3.0-63.0) days (P < 0,001); and 24.0 (3.0-140.0) versus 14.0 (3.0-80.0) days (P = 0.002), respectively., Conclusions: In critically ill patients, there was a reduction in hemoglobin with increasing length of ICU stay. Moreover, transfusion was associated with worse prognoses.

Early diagnosis gives melanoma patients the best chance for long term survival. However discrimination of an early melanoma from an unusual/atypical benign nevus can represent a significant challenge. There are no current pathological markers to definitively define malignant potential in these indeterminate lesions. Thus, there is a need for improved diagnostic tools. Chromosomal instability (CIN) is a hallmark of cancer and is markedly prevalent in melanoma. Advances in genomics have opened the door for the development of molecular tools to better segregate benign and malignant lesions. This paper focuses on CIN in melanoma and the role of current diagnostic approaches.

The detection and control of bacteria is extremely important in the safety of food products and health systems. The conventional microbiological methods based on culture enrichment techniques and plating procedures are highly sensitive and selective for bacterial detection but are expensive, cumbersome and time-consuming. Here we report the development of a simple and sensitive bioassay to detect Escherichia coli (E. coli) bacteria by using self assembled pH-responsive polymeric micelles that have been bioconjugated to anti-E. coli (capturing agent). Poly(ethylene glycol-b-trimethylsilyl methacrylate), containing silicon moieties that can be cleaved under mildly acidic conditions, was synthesized and self-assembled into micelles, that were loaded with a fluorescent dye (1-methylpyrene). The polymer silicon protecting groups are used as a tool to remotely activate the dye release by means of pH. The high sensitivity of the newly developed bioassay, which is capable of detecting 15 bacteria per milliliter of solution, is due to an amplification effect generated by the optical signal of millions of fluorophores released from a single micelle upon attachment to a bacterium. Fluorescence probing involves the measurements of changes in the emission spectra, through the disappearance of the excimer band, which only occurs when the dye molecules are trapped within the polymeric micelles., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background and Objectives: Low central venous oxygen saturation (ScvO₂) indicates an imbalance between cellular oxygen supply and consumption and, consequently, worse prognosis for critical patients. However, it is not clear what the value of this marker in surgical patients. The objective of the present study was to evaluate whether low perioperative ScvO₂ determines a worse prognosis., Methods: This is a 6-month observational study carried on in a tertiary hospital. Patients who needed to be in the intensive care unit (ICU) postoperatively, with age ≥ 18 years, who underwent large surgeries, were included. Patients who underwent palliative surgeries and those with severe heart failure were excluded. Levels of ScvO₂ were measured before the surgery, during the procedure, and after the surgery in the ICU., Results: Sixty-six patients were included in this study, but 25.8% of them did not survive. Mean ScvO₂ levels were higher intraoperatively, 84.7 ± 8.3%, than preoperatively and in the ICU, 74.1 ± 7.6% and 76.0 ± 10.5% (p = 0.0001), respectively. However, only preoperative SvcO₂ levels of non-surviving patients were significantly lower than those who survived. By logistic regression, preoperative ScvO₂, OR = 0.85 (95% CI 0.74-0.98) (p = 0.02), was an independent factor of in-hospital mortality. Patients with preoperative ScvO₂ < 70% had greater need of intraoperative blood transfusion (80.0% versus 37.0%, p = 0.001) and volume replacement, 8,000.0 (6,500.0-9,225.0) mL versus 6,000.0 (4,500.0-8,500.0) mL (p = 0.04), with greater chances of postoperative complications (75% versus 45.7%, p = 0.02) and longer time in the ICU, 4.0 (20.0-5.0) days versus 3.0 (1.7-4.0) days (p = 0.02)., Conclusions: Intraoperative ScvO₂ levels are higher than those both in the pre- and postoperative period. However, low preoperative ScvO₂ determines worse prognosis., (© 2010 Elsevier Editora Ltda. All rights reserved.)

Objectives: An increased lactate level is classically considered a marker for poorer prognosis, however little information is available on intraoperative lactate's kinetics and its connection with prognosis. This study aimed to evaluate the time when perioperative lactate is most relevant for prognosis., Methods: This was an observational prospective study conducted in a tertiary hospital. Patients with requested intensive care unit postoperative stay, aged > 18 years, undergoing major surgery were included. Palliative surgery patients and those with heart and/or severe liver failure were excluded. Arterial lactate levels were measured immediately before the surgery start (T0), after anesthesia induction (T1), 3 hours after the surgery start (T2), intensive care unit admission (T3) and 6 hours after the intensive care unit admission (T4)., Results: Sixty seven patients were included. The mean lactate values for the patients' T0, T1, T2 and T4 were 1.5 ± 0.8 mmol/L, 1.5 ± 0.7 mmol/L, 1.8 ± 1.2 mmol/L, 2.7 ± 1.7 mmol/L and 3.1 ± 2.0 mmol/L, respectively. The hospital mortality rate was 25.8%, and surviving and non-surviving patients lactate values in the intensive care unit were 2.5 ± 1. and 4.8 ± 2.8 mmol/L (P < 0.0001), respectively. The other times measurements showed no statistically significant differences between the groups., Conclusions: In surgical patients, intraoperative arterial lactate levels failed to show a predictive value; however during the postoperative period, this assessment was shown to be useful for hospital mortality prediction.

Knowledge of the fragmentation mechanisms of lactones and their behaviour under electrospray ionization (ESI) conditions can be extended to larger and more complex natural products that contain an alpha,beta-unsaturated gamma-lactone moiety in their structure. Moreover, little is known about the gas-phase behaviour of alpha,beta-unsaturated gamma-lactones linked or fused to sugars. Therefore, five alpha,beta-unsaturated gamma-lactones (butenolides) fused to a pyranose ring, recently synthesized compounds with potential relevance regarding their biological properties, were investigated using ESI-MS and ESI-MS/MS in both positive and negative ion modes. Their fragmentation mechanisms and product ion structures were compared. It was observed that two isomers could be unambiguously distinguished in the negative ion mode by the fragmentation pathways of their deprotonated molecules as well as in the positive ion mode by the fragmentation pathways of either the protonated or the sodiated molecule. Fragmentation mechanisms are proposed taking into account the MS/MS data and semi-empirical calculations using the PM6 Hamiltonean. The semi-empirical calculations were also very useful in determining the most probable protonation and cationization sites., (2010 John Wiley & Sons, Ltd.)

Objective: To analyze the prevalence and symptoms of asthma in students of the Brazilian Amazon municipality of Alta Floresta-MT., Methods: Cross-sectional study on the prevalence of asthma in 6 and 7 year-old children and 13 to 14 year-old adolescents, using the Study of Asthma and Allergies in Childhood - ISAAC method, phase I in 2007. Students who answered affirmatively question 2 - "presence of wheezing in the past 12 months" were considered asthmatic., Results: Of the total 2,071 students, 1,072 (51.7%) were children and 999 (48.3%) were teenagers. The prevalence of asthma was 21.4% among schoolchildren, and 12.4% among adolescents (chi2 = 29.29; rho = 0.00). Children presented a higher prevalence than adolescents of the following asthma symptoms: wheezing sometime in life (49.9%), wheezing in the past 12 months (21.4%), 1 to 3 wheezing attacks in the past 12 months (16.4%), and dry cough at night (38.2%). Regarding physician-diagnosed asthma, no difference was observed between the two age groups, with a prevalence of around 6.0%. Male schoolchildren presented a higher prevalence of asthma, physician-diagnosed asthma and four or more wheezing episodes in the past 12 months (rho < 0.05). Male adolescents presented the highest prevalence of strong wheezing affecting speech (rho < 0.05)., Conclusion: Alta Floresta presents one of the highest prevalences of asthma in Latin America among schoolchildren in the 6 and 7 year-old age group.

Objective: To analyze the distribution of hospitalizations of children for asthma in the states comprising the Brazilian Amazon, as well as the variations of hospitalization according to climatic seasonality., Methods: A descriptive study of the distribution of hospitalizations for asthma of individuals aged 0 to 14 years living in the Brazilian Amazon, according to trend, spatial distribution, and climatic seasonality over the period from 2001 to 2007. We used the database of authorizations for hospitalizations (AIH) of the Hospital Information System (SIH/SUS) of the Brazilian Ministry of Health., Results: The spatial distribution of hospitalizations for asthma resembles the configuration of the "arc of deforestation," mainly in the states of Rondônia and Maranhão. The distribution of annual hospitalizations for asthma decreased from 8.1 to 2.6 hospitalizations/1,000 inhabitants during the period. There was a peak of hospitalizations in March and May in all states. The seasonal differences were on average 10%, with the highest rates during the rainy season., Conclusion: We concluded that hospitalizations for asthma are more frequent in the months of more intense rainfall, with greater magnitude in the states comprising the "arc of deforestation" in the Brazilian Amazon, especially Rondônia and Maranhão.

We tested 2655 Peruvian men who have sex with men for the presence of retroviral infection. Human T cell lymphotropic virus type 1 (HTLV-1) was detected in 48 (1.8%) of the patients, HTLV-2 was detected in 28 (1.1%), and HTLV-1 and HTLV-2 were both detected in 5 (0.2%). Human immunodeficiency virus infection was detected in 329 (12.4%) of the patients; 24 (7.3%) had HTLV coinfection. Risk factors for HTLV-1 and HTLV-2 infection varied with sexual role.

Purpose: To prospectively compare laser in situ keratomileusis (LASIK) flaps created with a femtosecond laser or a mechanical microkeratome and analyze the effect of the postoperative measurement interval on estimated femtosecond flap thickness using ultrasound (US) pachymetry., Setting: Department of Ophthalmology, University Hospital of Coimbra, and Coimbra Surgical Centre, Coimbra, Portugal., Methods: Flaps were created with a Hansatome Zero Compression microkeratome (Group 1), Zyoptix XP keratome (Group 2), or IntraLase 60 kHz femtosecond laser (Groups 3 and 4). Flap thickness was determined by intraoperative US pachymetry immediately after flap creation in Groups 1, 2, and 3. In Group 4, pachymetry was performed 20 minutes after the laser treatment. The main outcome measures were flap thickness and deviation from the target value., Results: Eighty patients had LASIK for myopia or myopic astigmatism. The mean flap thickness was 149.1 microm +/- 24.9 (SD) in Group 1, 124.7 +/- 23.8 microm in Group 2, 143.1 +/- 18.4 microm in Group 3, and 115.5 +/- 12.5 microm in Group 4. The difference in flap thickness between Group 3 and Group 4 was statistically significant (P<.01). The flap thickness deviation from the target value was 22.8 microm in Group 1, 19.0 microm in Group 2, 26.1 microm in Group 3, and 10.4 microm in Group 4., Conclusions: Results indicate that the time of measurement after femtosecond affects the estimated flap thickness. Waiting 20 minutes after laser treatment permitted easier separation and may eliminate the effect of variable corneal dehydration on flap measurement by subtraction pachymetry.

Objective: To analyze the prevalence of asthma and asthma symptoms in students of two distinct age brackets residing in the city of Tangará da Serra, Brazil., Methods: Cross-sectional, population-based study of the prevalence of asthma in children from 6 to 7 years of age and adolescents from 13 to 14, using the standardized International Study of Asthma and Allergies in Childhood, phase 1 questionnaire, validated for use in Brazil. Students who responded affirmatively to question 2 (presence of wheezing in the preceding 12 months) were classified as suffering from asthma., Results: The study comprised 3,362 students, of whom 1,634 (48.6%) were children and 1,728 (51.4%) were adolescents. Of the 1,634 children, 816 (49.9%) were male, and 818 (50.1%) were female. Of the 1,728 adolescents, 773 (45.0%) were male, and 955 (55.0%) were female. The prevalence of asthma among the children was 25.2%, whereas that among the adolescents was 15.9% (chi2 = 8.34; p = 0.00). The children presented higher prevalences of the following symptoms of asthma than did the adolescents: wheezing ever (54.3%), nocturnal dry cough (43.9%), wheezing in the preceding 12 months (25.2%), and from 1 to 3 attacks of wheezing in the preceding 12 months (19.1%). There were no differences between the two groups regarding physician-diagnosed asthma (approximately 4.5%). There were no statistical differences regarding the prevalence of asthma by gender in the two groups., Conclusions: Tangará da Serra has a high prevalence of asthma in children and adolescents, and this result is compatible with other studies carried out in Brazil and Latin America using the same methodology.