Medicine

Myotonic dystrophy type 1 (DM1) is a genetic disorder that causes muscle weakness and myotonia. In DM1 patients, cardiac electrical manifestations include conduction defects and atrial fibrillation. DM1 results in the expansion of a CTG transcribed into CUG-containing transcripts that accumulate in the nucleus as RNA foci and alter the activity of several splicing regulators. The underlying pathological mechanism involves two key RNA-binding proteins (MBNL and CELF) with expanded CUG repeats that sequester MBNL and alter the activity of CELF resulting in spliceopathy and abnormal electrical activity. In the present study, we identified two DM1 patients with heart conduction abnormalities and characterized their hiPSC lines. Two differentiation protocols were used to investigate both the ventricular and the atrial electrophysiological aspects of DM1 and unveil the impact of the mutation on voltage-gated ion channels, electrical activity, and calcium homeostasis in DM1 cardiomyocytes derived from hiPSCs. Our analysis revealed the presence of molecular hallmarks of DM1, including the accumulation of RNA foci and sequestration of MBNL1 in DM1 hiPSC-CMs. We also observed mis-splicing of SCN5A and haploinsufficiency of DMPK. Furthermore, we conducted separate characterizations of atrial and ventricular electrical activity, conduction properties, and calcium homeostasis. Both DM1 cell lines exhibited reduced density of sodium and calcium currents, prolonged action potential duration, slower conduction velocity, and impaired calcium transient propagation in both ventricular and atrial cardiomyocytes. Notably, arrhythmogenic events were recorded, including both ventricular and atrial arrhythmias were observed in the two DM1 cell lines. These findings enhance our comprehension of the molecular mechanisms underlying DM1 and provide valuable insights into the pathophysiology of ventricular and atrial involvement.

Generating atrial-like cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) is crucial for modeling and treating atrial-related diseases, such as atrial arrythmias including atrial fibrillations. However, it is essential to obtain a comprehensive understanding of the electrophysiological properties of these cells. The objective of the present study was to investigate the molecular, electrical, and biophysical properties of several ion channels, especially NaV1.5 channels, in atrial hiPSC cardiomyocytes. Atrial cardiomyocytes were obtained by the differentiation of hiPSCs treated with retinoic acid (RA). The quality of the atrial specification was assessed by qPCR, immunocytofluorescence, and western blotting. The electrophysiological properties of action potentials (APs), Ca2+ dynamics, K+ and Na+ currents were investigated using patch-clamp and optical mapping approaches. We evaluated mRNA transcript and protein expressions to show that atrial cardiomyocytes ex...

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Chronic diseases are the primary cause of mortality worldwide, accounting for 67% of deaths. One of the major challenges in developing new treatments is the lack of understanding of the exact underlying biological and molecular mechanisms. Chronic cardiovascular diseases are the single most common cause of death worldwide, and sudden deaths due to cardiac arrhythmias account for approximately 50% of all such cases. Traditional genetic screening for genes involved in cardiac disorders is laborious and frequently fails to detect the mutation that explains or causes the disorder. However, when mutations are identified, human induced pluripotent stem cells (hiPSCs) derived from affected patients make it possible to address fundamental research questions directly relevant to human health. As such, hiPSC technology has recently been used to model human diseases and patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs) thus offer a unique opportunity to investigate potential disease-causing genetic variants in their natural environment. The purpose of this review is to present the current state of knowledge regarding hiPSC-CMs, including their potential, limitations, and challenges and to discuss future prospects.

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Voltage gated sodium channels (Na v channels) play an important role in nociceptive transmission. They are intimately tied to the genesis and transmission of neuronal firing. Five different isoforms (Na v 1.3, Na v 1.6, Na v 1.7, Na v 1.8, and Na v 1.9) have been linked to nociceptive responses. A change in the biophysical properties of these channels or in their expression levels occurs in different pathological pain states. However, the precise involvement of the isoforms in the genesis and transmission of nociceptive responses is unknown. The aim of the present study was to investigate the synergy between the different populations of Na v channels that give individual neurons a unique electrophysical profile. We used the patch-clamp technique in the whole-cell configuration to record Na v currents and action potentials from acutely dissociated small diameter DRG neurons (<30 μm) from adult rats. We also performed single cell qPCR on the same neurons. Our results revealed that there is a strong correlation between Na v currents and mRNA transcripts in individual neurons. A cluster analysis showed that subgroups formed by Na v channel transcripts by mRNA quantification have different biophysical properties. In addition, the firing frequency of the neurons was not affected by the relative populations of Na v channel. The synergy between populations of Na v channel in individual small diameter DRG neurons gives each neuron a unique electrophysiological profile. The Na v channel remodeling that occurs in different pathological pain states may be responsible for the sensitization of the neurons.

Background and Aim-The action potential plateau of Purkinje fibers is particularly sensitive to tetrodotoxin (TTX) and this could be due to a TXX-sensitive Na + current. The expression of TTXsensitive neuronal Na V 1.1 and Na V 1.2 isoforms has been reported in canine Purkinje myocytes. Our aim was to investigate by means of biochemical and functional techniques whether the TTX-sensitive skeletal Na V 1.4 isoform is also expressed in canine cardiac Purkinje myocytes. Methods and Results-Using Na V 1.4 specific primers, a PCR product corresponding to Na V 1.4 was amplified from canine Purkinje fibers RNA and confirmed by sequencing and megablast of the gene bank. Confocal indirect immunostaining using anti-Na V 1.4 antibody demonstrates distinct sarcolemmal staining pattern compared to that of the cardiac isoform Na V 1.5. Expression of Na V 1.4 in tsA201 cells yielded a TTX-sensitive Na + current with an IC 50 of 10 nM. Conclusions-These results demonstrate the expression of the TTX-sensitive Na V 1.4 channel in canine cardiac Purkinje myocytes. This novel finding suggests a role of Na V 1.4 channel in Purkinje myocytes and thus has important clinical implications for the mechanisms and management of ventricular arrhythmias originating in the Purkinje network.

B rugada syndrome (BS) is characterized by a unique electro- cardiographic (ECG) pattern of right bundle branch block with ST elevation in the right precordial leads and can result in malignant ventricular tachycardia and sudden cardiac death (1,2). Transient forms of the disease in which the ECG normalizes for a period of time have been described. Administration of sodium channel blockers unmasks abnormal ECGs in patients with transient normalized ECGs. Approximately 20% of BS patients have mutations in SCN5A, which encodes the alphasubunit of the human cardiac voltage-dependent sodium channel (hNa v 1.5) (3). This implies that another or other genes are responsible for this syndrome, but their location and products are not yet known (4). However, a second locus has been recently identified that overlaps with the SCN5A gene. In this study (4), the involvement of SCN5A was excluded by direct sequencing.

Mortality rate is high in psychiatric patients versus general population. An important cause of this increased mortality is sudden cardiac death (SCD) as a major side-effect of psychotropic drugs. These SCDs generally result from arrhythmias occurring when the posology is high and may attain a toxic threshold but also at dosages within therapeutic range, in the presence of risk factors. There are three kinds of risk factors: physiological (e.g., low cardiac rate of sportsmen), physiopathological (e.g., hepatic insufficiency, hypothyroidism) and "therapeutic" (due to interactions between psychotropic drugs and other medicines). Association of pharmacological agents may increase the likelihood of SCDs either by (i) a pharmacokinetic mechanism (e.g., increased torsadogenic potential of a psychotropic drug when its destruction and/or elimination are compromised) or (ii) a pharmacodynamical mechanism (e.g., mutual potentiation of proarrhythmic properties of two drugs). In addition, some psychotropic drugs may induce sudden death in cases of pre-existing congenital cardiopathies such as (i) congenital long QT syndrome, predisposing to torsade de pointes that eventually cause syncope and sudden death. (ii) A Brugada syndrome, that may directly cause ventricular fibrillation due to reduced sodium current through Nav1.5 channels. Moreover, psychotropic drugs may be a direct cause of cardiac lesions also leading to SCD. This is the case, for example, of phenothiazines responsible for ischemic coronaropathies and of clozapine that is involved in the occurrence of myocarditis. The aims of this work are to delineate: (i) the risk of SCD related to the use of psychotropic drugs; (ii) mechanisms involved in the occurrence of such SCD; (iii) preventive actions of psychotropic drugs side effects, on the basis of the knowledge of patient-specific risk factors, documented from clinical history, ionic balance, and ECG investigation by the psychiatrist.

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

> Les canaux ioniques dépendants du voltage (VGIC) représentent une large famille de protéines canalaires assurant le passage d'ions de part et d'autre de la membrane plasmique. Les VGIC ont la particularité d'être dotés d'un domaine senseur de voltage (VSD). Cette unité régule l'activité des VGIC en fonction des variations de potentiel membranaire. Récemment, des mutations décrites dans le VSD ont conduit à la découverte d'une nouvelle voie de perméation directement localisée au sein de ce domaine : le pore oméga. Au vu du grand nombre de protéines présentant un VSD et de leur rôle crucial dans diverses fonctions physiologiques, déchiffrer le potentiel pathogénique du pore oméga s'avère désormais essentiel. < Le mouvement du segment S4 possédant de 3 à 7 charges positives (apportées par des arginines et des lysines) induit un changement de conformation du pore aboutissant à son ouverture, et donc au passage des ions. Récemment, plusieurs études ont montré que des modifications du VSD peuvent générer une autre voie pour le passage des ions appelée pore oméga. L'objectif de cette revue est de présenter le concept de pore oméga, ses propriétés biophysiques ainsi que son potentiel pathologique.

Cardiomyocytes derived from patient-specific induced pluripotent stem cells (iPSC-CMs) successfully reproduce the mechanisms of several channelopathies. However, this approach involve cell reprogramming from somatic tissue biopsies or genomic editing in healthy iPSCs for every mutation found and to be investigated. We aim to knockout (KO) Na V 1.5, the cardiac sodium channel, in a healthy human iPSC line, characterize the model and then, use it to express variants of Na V 1.5. We develop a homozygous Na V 1.5 KO iPSC line able to differentiate into cardiomyocytes with CRISPR/ Cas9 tool. The Na V 1.5 KO iPSC-CMs exhibited an organized contractile apparatus, spontaneous contractile activity, and electrophysiological recordings confirmed the major reduction in total Na + currents. The action potentials (APs) exhibited a reduction in their amplitude and in their maximal rate of rise. Voltage optical mapping recordings revealed that the conduction velocity Ca 2+ transient waves propagation velocities were slow. A wild-type (WT) Na V 1.5 channel expressed by transient transfection in the KO iPSC-CMs restored Na + channel expression and AP properties. The expression of Na V 1.5/ delQKP, a long QT type 3 (LQT3) variant, in the Na V 1.5 KO iPSC-CMs showed that dysfunctional Na + channels exhibited a persistent Na + current and caused prolonged AP duration that led to arrhythmic events, characteristics of LQT3. Action potential APD Action potential duration CRISPR/Cas9 Clustered regularly interspaced short palindromic repeats/associated protein 9 CHO Chinese hamster ovary CICR Calcium-induced calcium release cTnT Cardiac troponin T DAD Delayed afterdepolarization DelQKP Deletion of three amino acids QKP (glutamine, lysine, proline) dV/dt max Upstroke velocity EAD Early postdepolarization HEK Human embryonic kidney iPSC-CM Cardiomyocytes derived from induced pluripotent stem cells KO Knock-out LQT3 Long QT syndrome type 3 Mlc2v Ventricular myosin light chain 2 OM Optical mapping SCN5a Sodium voltage-gated channel alpha subunit 5 TdP Torsade de pointes TTX Tetrodotoxin VGSC Voltage-gated sodium channel WT Wild type

Voltage gated sodium channels (Na V ) are broadly expressed in the human body. They are responsible for the initiation of action potentials in excitable cells. They also underlie several physiological processes such as cognitive, sensitive, motor, and cardiac functions. The Na V 1.5 channel is the main Na V expressed in the heart. A dysfunction of this channel is usually associated with the development of pure electrical disorders such as long QT syndrome, Brugada syndrome, sinus node dysfunction, atrial fibrillation, and cardiac conduction disorders. However, mutations of Na v 1.5 have recently been linked to the development of an atypical clinical entity combining complex arrhythmias and dilated cardiomyopathy. Although several Na v 1.5 mutations have been linked to dilated cardiomyopathy phenotypes, their pathogenic mechanisms remain to be elucidated. The gating pore may constitute a common biophysical defect for all Na V 1.5 mutations located in the channel's VSDs. The creation of such a gating pore may disrupt the ionic homeostasis of cardiomyocytes, affecting electrical signals, cell morphology, and cardiac myocyte function. The main objective of this article is to review the concept of gating pores and their role in structural heart diseases and to discuss potential pharmacological treatments.

Voltage gated sodium channels (Na v ) are transmembrane proteins responsible for action potential initiation. Mutations mainly located in the voltage sensor domain (VSD) of Na v 1.5, the cardiac sodium channel, have been associated with the development of arrhythmias combined with dilated cardiomyopathy. Gating pore currents have been observed with three unrelated mutations associated with similar clinical phenotypes. However, gating pores have never been associated with mutations outside the first domain of Na v 1.5. The aim of this study was to explore the possibility that gating pore currents might be caused by the Na v 1.5 R225P and R814W mutations (R3, S4 in DI and DII, respectively), which are associated with rhythm disturbances and dilated cardiomyopathy. Na v 1.5 WT and mutant channels were transiently expressed in tsA201 cells. The biophysical properties of the alpha pore currents and the presence of gating pore currents were investigated using the patch-clamp technique. We confirmed the previously reported gain of function of the alpha pores of the mutant channels, which mainly consisted of increased window currents mostly caused by shifts in the voltage dependence of activation. We also observed gating pore currents associated with the R225P and R814W mutations. This novel permeation pathway was open under depolarized conditions and remained temporarily open at hyperpolarized potentials after depolarization periods. Gating pore currents could represent a molecular basis for the development of uncommon electrical abnormalities and changes in cardiac morphology. We propose that this biophysical defect be routinely evaluated in the case of Na v 1.5 mutations on the VSD.

Genome-wide association studies (GWAS) have identified thousands of genetic variants linked to the risk of human disease. However, GWAS have so far remained largely underpowered in relation to identifying associations in the rare and low-frequency allelic spectrum and have lacked the resolution to trace causal mechanisms to underlying genes 1 . Here we combined whole-exome sequencing in 392,814 UK Biobank participants with imputed genotypes from 260,405 FinnGen participants (653,219 total individuals) to conduct association meta-analyses for 744 disease endpoints across the protein-coding allelic frequency spectrum, bridging the gap between common and rare variant studies. We identified 975 associations, with more than one-third being previously unreported. We demonstrate population-level relevance for mutations previously ascribed to causing single-gene disorders, map GWAS associations to likely causal genes, explain disease mechanisms, and systematically relate disease associations to levels of 117 biomarkers and clinical-stage drug targets. Combining sequencing and genotyping in two population biobanks enabled us to benefit from increased power to detect and explain disease associations, validate findings through replication and propose medical actionability for rare genetic variants. Our study provides a compendium of protein-coding variant associations for future insights into disease biology and drug discovery. Inherited variations in protein-coding and non-coding DNA have a role in the risk, onset and progression of human disease. Traditionally, geneticists have dichotomized diseases as either caused by coding mutations in single genes that tend to be rare, highly penetrant and frequently compromise survival and reproduction (often termed 'Mendelian' diseases), or as common diseases that show a complex pattern of inheritance influenced by the joint contributions of hundreds of low-impact, typically non-coding genetic variants (often termed 'complex' diseases). For both rare and common conditions, large human cohorts systematically characterized for a respective trait of interest have enabled the identification of thousands of disease-relevant variants through either sequencing-based approaches or GWAS. Nevertheless, the exact causal alleles and mechanisms that underlie associations of genetic variants to disease have so far remained largely elusive 1 . In recent years, population biobanks have been added to the toolkit for disease gene discovery. Biobanks provide the opportunity to simultaneously investigate multiple traits and diseases at once and uncover relationships between previously unconnected phenotypes. For instance, the UK Biobank (UKB) is a resource that captures detailed phenotype information matched to genetic data for more than 500,000 individuals and, since its inception, has facilitated biomedical discoveries at an unprecedented scale 2 . We and others have recently reported on the ongoing efforts to sequence the exomes of all UKB participants and link genetic findings to a broad range of phenotypes . We also established FinnGen (FG) (), an academic-industry collaboration to identify genotype-phenotype correlations in the Finnish founder population with the aim of better understanding how the genome affects health. Finland is a well-established genetic isolate and a unique gene pool distinguishes Finns from other Europeans 7 . The distinct Finnish haplotype structure is characterized by large blocks of co-inherited DNA in linkage disequilibrium and an enrichment for alleles that are rare in other populations, but can still be confidently imputed from genotyping data even in the rare and ultra-rare allele frequency spectrum . Through combining imputed genotypes with detailed phenotypes ascertained through national registries, FG holds the promise to provide particular insights into the so far little examined allele frequency spectrum between 0.1 and 2%, where both sequencing studies and GWAS have so far remained largely underpowered in relation to identifying associations with disease. This spectrum includes many coding variants with moderate to large effect sizes that can help

The human cardiac sodium channel Na v 1.5 encoded by the SCN5A gene plays a critical role in cardiac excitability and the propagation of action potentials. Na v 1.5 dysfunctions due to mutations cause cardiac diseases such as the LQT3 form of long QT syndrome, conduction disorders, and Brugada syndrome (BrS). They have also recently been associated with dilated cardiomyopathy. BrS is characterized by coved ST-segment elevation on surface ECGs and lethal ventricular arrhythmias in an apparently structurally normal heart. Na v 1.5 mutations that cause BrS result in a loss of channel function. Our aim was to functionally characterize two novel Na v 1.5 mutations (A124D and V1378M) in BrS patients. Wild-type (WT) and mutant Na v 1.5 channels were expressed in tsA201 cells in the presence of the β 1auxiliary subunit. The patch-clamp technique and immunocytochemistry approaches were used to study the mutant channels and their cellular localization. The two mutant channels displayed a dramatic reduction in current density but had normal gating properties. The reduction in current density was caused by the retention of channel proteins in the endoplasmic reticulum (ER). Mutant channel retention could be partially reversed by incubating transfected cells at 25˚C and by treating them with mexiletine (for V1378M but not A124D), or with curcumin or thapsigargin, two drugs that target ER resident proteins. It is likely that the clinical phenotypes observed in these two BrS patients were related to a surface expression defect caused by ER retention.

Cardiovascular diseases are associated with several morbidities and are the most common cause of worldwide disease-related fatalities. Studies show that treatment and outcome-related differences for cardiovascular diseases disproportionately affect minorities in the United States. The emergence of ethnic and racial differences in sudden cardiac death (SCD) and related ion channelopathies complicates cardiovascular disease prevention, diagnosis, management, prognosis, and treatment objectives for patients and physicians alike. This review compiles and synthesizes current research in cardiac ion channelopathies and genetic disorders in Asian populations, an underrepresented population in cardiovascular literature. We first present a brief introduction to SCD, noting relevant observations and statistics from around the world, including Asian populations. We then examined existing differences between Asian and White populations in research, treatment, and outcomes related to cardiac ion...

Dilated cardiomyopathy (DCM) is a structural heart disease that causes dilatation of cardiac chambers and impairs cardiac contractility. The SCN5A gene encodes Nav1.5, the predominant cardiac sodium channel alpha subunit. SCN5A mutations have been identified in patients with arrhythmic disorders associated with DCM. The characterization of Nav1.5 mutations located in the voltage sensor domain (VSD) and associated with DCM revealed divergent biophysical defects that do not fully explain the pathologies observed in these patients. The purpose of this study was to characterize the pathological consequences of a gating pore in the heart arising from the Nav1.5/R219H mutation in a patient with complex cardiac arrhythmias and DCM. We report its properties using cardiomyocytes derived from patient-specific human induced pluripotent stem cells. We showed that this mutation generates a proton leak (called gating pore current). We also described disrupted ionic homeostasis, altered cellular m...

Background: Femtosecond Laser Assisted Cataract Surgery has benefits and drawbacks, our work was to study its effects on the corneal integrity. Objectives: To study the effect of femtosecond laser assisted cataract surgery on the corneal integrity in comparison with phacoemulsification. Patients and methods; This prospective comparative randomized controlled study was done at Cortoba eye center, Cairo. It was conducted on 40 eyes suffering from cataract graded from 2 to 4. They were divided into 2 equal groups. Group (A) femtosecond laser assisted cataract surgery was done using Victus Femtosecond Laser Platform (Bausch and Lomb). Group (B) conventional phacoemulsification was done using Alcon Infiniti Phaco Machine. Full preoperative ophthalmological examination, best corrected visual acuity (BCVA), corneal thickness and endothelial cell count were done and repeated postoperatively. Main outcome measures included visual acuity, corneal oedema, corneal thickness, and endothelial cell count. Data was collected and statistically analyzed. Results: Regarding corneal thickness; there was no significant difference between groups and it significantly increased in both groups. Corneal endothelial cell count in Group B was significantly lower after one month and it significantly decreased in both groups but more in group B. Conclusion: Femtosecond laser assisted cataract has a transient corneal edema and loss of endothelial cell count with less effects on the corneal integrity than phacoemulsification.

Background: Ten years was passed since the first Femtosecond Laser Assisted Cataract Surgery (FLACS) platform was introduced to the Egyptian market with hope for cataract patients. Objectives: To report and assess femtosecond laser assisted cataract surgery's efficiency and safety utilizing Victus femtosecond laser platform used in the Egyptian market. Patients and methods: This retrospective investigation was conducted at a private facility that has Egypt's first FLACS platform. It was conducted 10 years ago on 20 eyes that had cataract grade III. For them Femtosecond laser assisted cataract surgery was done using Victus Femtosecond Laser Platform (Technolas Bausch and Lomb). 20 eyes were planned as a control group utilizing conventional cataract extraction. Preoperative slit lamp examination, best corrected visual acuity and endothelial cell count were done and repeated postoperatively. Main outcome measures contained visual acuity and endothelial cell count. Data were collected and analyzed statistically. Results: Regarding postoperative visual acuity it was significantly better with FLACS and improved after one week and one month, beside that endothelial cell loss was less with it. In comparison to traditional cataract extraction, femtosecond laser assisted cataract surgery (FLACS) using the Victus femtosecond laser platform was a successful and secure technique.

Background/objective This study aimed to investigate the visual performance of a new extended depth-of-focus intraocular lens (EDOF-IOL). Subjects/methods In this multicenter, prospective, observational study, we enrolled 97 patients who underwent cataract surgery or refractive lens exchange with implantation of the Mini Well EDOF-IOL (SIFI, Italy). Patients underwent postoperatively the following examinations between 4 and 8 weeks after surgery: corrected distance visual acuity (CDVA), reading speed with Radner's chart, distance-corrected near visual acuity (DCNVA), defocus curve, contrast sensitivity, and haloes quantitative assessment. Results In the whole sample, the mean monocular CDVA and DCNVA were, respectively, 0.02 ± 0.07 logMAR and 0.38 ± 0.15 logRAD (logarithm of the reading acuity determination). In the 67 bilaterally implanted patients, binocular CDVA and DCNVA were better (0.00 ± 0.05 logMAR and 0.26 ± 0.13 logRAD) than the corresponding monocular values (p = 0.02 and p = 0.0002, respectively). Ninety-two percent of patients bilaterally implanted reached a binocular reading speed >80 words per minute at a 0.5 logRAD print size (corresponding to the common book print size). The defocus curves showed that the EDOF-IOL provided increased depth of focus through 2.0 D of defocus, with the best performance at 1.0 and 1.5 D. Contrast sensitivity was within normal limits at all spatial frequencies. The mean visual disturbance index was 0.08 ± 0.12, suggesting low night visual disturbances. Conclusions The new EDOF-IOL provided good visual acuity for distance, intermediate, and near vision, with no loss of contrast sensitivity and low risk of night visual disturbances.

Purpose: To illustrate the advantages and limitations of Small Incision Lenticule Extraction (SMILE) over Laser Assisted Intrastromal Keratomileusis (LASIK) in the correction of myopia and myopic astigmatism. The two procedures are analysed and compared for the technical aspects. While LASIK directly depends on the laser effi cacy to get the refractive change, SMILE only depends on the computer ability to design the refractive lenticule. The loss in precision taking place in the peripheral cornea with LASIK is not possible with SMILE. Tissue consumption and postoperative dry eye are also lower with SMILE. Procedure abortion has less consequences with SMILE. From a clinical point of view, refractive and visual results with SMILE are similar as those of Wavefront Optimized and Wavefront Guided LASIK, but re-operations are easier after LASIK than after SMILE. When indicated, SMILE is better than LASIK from a technical and procedural standpoint and is equal to Wavefront Lasik as for the obtained results. LASIK is still more versatile and it is better for re-operations.

Background: Cataract surgery is mainly performed under topical anesthesia achieved either by tetracaine solution (0.5%-1.0%) or gel (0.5%), or by 2% lidocaine gel. This paper reviews the current knowledge about these two drugs, with special emphasis on a published prospective comparison between them. The main pharmacological aspects of topical anesthetic agents are summarized, explaining the difference between the ester (tetracaine) and the amide (lidocaine) compounds. Tetracaine is available as single-use eye drops, or as a multidose gel containing benzalkonium chloride, a preservative not contained in the multidose lidocaine gel. A literature search was performed, using "tetracaine", "tetracaine gel", "lidocaine", "lidocaine gel", "lidocaine jelly", and "cataract surgery" as keywords, and compiling cross-references. A total of 25 studies were identified and included in this review. Of them, seven were uncontrolled studies describing different experiences with the drugs of interest, and 18 were controlled studies. Six studies directly compared tetracaine eye drops or gel with lidocaine gel before cataract surgery. Results: Both tetracaine solution and gel and lidocaine gel proved to be effective in providing analgesia before cataract surgery. Both drugs were comparable with needle injection anesthesia when intracameral lidocaine was added to topical treatment. Direct comparisons indicate better activity for tetracaine when used at the 1% concentration in single-dose units, or in the gel form at a 0.5% concentration. Patients showed a slight preference for the agent that caused the least discomfort when administered (lidocaine), while the surgical complication rate and the surgeon satisfaction were the same with either drug. Conclusion: Tetracaine solution and lidocaine gel were equally effective in providing topical anesthesia for cataract surgery in the published studies. Tetracaine was found to be better than lidocaine only if augmented by either increasing the concentration to 1% (solution) or by increasing the penetration by adding benzalkonium chloride (gel).

T-group and 0.54 ± 0.33 D in the S-group (p = 0.4). In the S-group, PRA was 0.73 ± 0.37 D, higher than the corresponding preoperative corneal astigmatism (p = 0.040). In the T-group, PRA was 0.58 ± 0.31 D; the variation was not statistically significant. Uncorrected VA was significantly better in the T-group vs the S-group (p = 0.007), and the best-corrected VA was comparable in the two groups. Conclusion The present study indicated that in eyes with very low preoperative astigmatism, 1.0 D toric IOLs were able to limit the increase of the PRA instead of those observed with the spherical IOLs. This could support the better uncorrected VA recorded in the T-group.

Purpose: This retrospective case-control study was conducted to quantitatively and qualitatively assess the visual impairment in eyes with Epithelial Basement Membrane Dystrophy (EBMD) after regular cataract surgery. Methods: EBMD pseudophakic eyes were compared with matched pseudophakic eyes free from surface disorders. At least 3 weeks after surgery we evaluated uncorrected and best-corrected distance visual acuity (UDVA and CDVA), objective aberrometry, Point Spread Function (PSF), Modulation Transfer Function (MTF), and patient complaints. Results: Twenty-five EBMD eyes and 25 control eyes (13 patients per group) were included. Nine patients per group had a monofocal IOL, and four patients had a trifocal IOL. All the EBMD patients complained of postoperative blurred vision with ocular discomfort; intensive use of lubricants induced subjective improvement only in eyes with monofocal IOLs. Postoperative mean UDVA was 0.19 ± 0.16 LogMAR in the EBMD eyes and 0.11 ± 0.04 LogMAR in th...

Introduction: To compare the short-term visual and aberrometric outcomes and the long-term capsulotomy incidence in a cohort of patients receiving IOLs with similar structural profile but with a hydrophobic matrix in one eye (PHOB group) and a hydrophilic matrix in the other one (PHIL group). Methods: In this retrospective, contralateral study, 26 patients sequentially undergoing phacoemulsification were implanted as mentioned above. Refraction and aberrometry were evaluated 6 months after surgery. For the quality of vision, the Hartmann-Shack optical aberration, Double-Pass Modulation Transfer Function (MTF), contrast sensitivity, and dysphotopsia results were compared. Capsulotomy was ascertained and dated by medical chart revision or phone call. Results: All the considered quantitative and qualitative visual parameters tested statistically comparable between PHIL and PHOB group. After 5 years, four patients (16.7%) in the PHOB group and five patients (20.8%) in the PHIL group underwent a Nd:YAG posterior capsulotomy (P [ 0.5). In this contralateral comparative study, the hydrophobic and hydrophilic matrix of the IOL similarly influenced the visual and aberrometric outcomes. Also the long-term laser capsulotomy incidence did not statistically differ between groups. The posterior IOL profile, rather than matrix hydrophilia, could consistently influence the posterior capsule opacification.

Purpose: To illustrate the advantages and limitations of Small Incision Lenticule Extraction (SMILE) over Laser Assisted Intrastromal Keratomileusis (LASIK) in the correction of myopia and myopic astigmatism. Materials and methods: The two procedures are analysed and compared for the technical aspects. While LASIK directly depends on the laser efficacy to get the refractive change, SMILE only depends on the computer ability to design the refractive lenticule. The loss in precision taking place in the peripheral cornea with LASIK is not possible with SMILE. Tissue consumption and postoperative dry eye are also lower with SMILE. Procedure abortion has less consequences with SMILE. From a clinical point of view, refractive and visual results with SMILE are similar as those of Wavefront Optimized and Wavefront Guided LASIK, but re-operations are easier after LASIK than after SMILE. Conclusion: When indicated, SMILE is better than LASIK from a technical and procedural standpoint and is e...

This study aimed to investigate the visual performance of a new extended depth-of-focus intraocular lens (EDOF-IOL). In this multicenter, prospective, observational study, we enrolled 97 patients who underwent cataract surgery or refractive lens exchange with implantation of the Mini Well EDOF-IOL (SIFI, Italy). Patients underwent postoperatively the following examinations between 4 and 8 weeks after surgery: corrected distance visual acuity (CDVA), reading speed with Radner&#39;s chart, distance-corrected near visual acuity (DCNVA), defocus curve, contrast sensitivity, and haloes quantitative assessment. In the whole sample, the mean monocular CDVA and DCNVA were, respectively, 0.02 ± 0.07 logMAR and 0.38 ± 0.15 logRAD (logarithm of the reading acuity determination). In the 67 bilaterally implanted patients, binocular CDVA and DCNVA were better (0.00 ± 0.05 logMAR and 0.26 ± 0.13 logRAD) than the corresponding monocular values (p = 0.02 and p = 0.0002, respectively). Ninety-two per...

To describe a large cohort of femtosecond laser-assisted cataract surgeries in terms of baseline characteristics and the related outcomes. Eighteen cataract surgery clinics in 9 European countries and Australia. Prospective multicenter case series. Data on consecutive eyes having femtosecond laser-assisted cataract surgery in the participating clinics were entered in the European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO). A trained registry manager in each clinic was responsible for valid reporting to the EUREQUO. Demographics, preoperative corrected distance visual acuity (CDVA), risk factors, type of surgery, type of intraocular lens, visual outcomes, refractive outcomes, and complications were reported. Complete data were available for 3379 cases. The mean age was 64.4 years ± 10.9 (SD) and 57.8% (95% confidence interval [CI], 56.1-59.5) of the patients were women. A surgical complication was reported in 2.9% of all cases (95% CI, 2.4-3.5). The me...

Background: Cataract surgery is mainly performed under topical anesthesia achieved either by tetracaine solution (0.5%-1.0%) or gel (0.5%), or by 2% lidocaine gel. This paper reviews the current knowledge about these two drugs, with special emphasis on a published prospective comparison between them. The main pharmacological aspects of topical anesthetic agents are summarized, explaining the difference between the ester (tetracaine) and the amide (lidocaine) compounds. Tetracaine is available as single-use eye drops, or as a multidose gel containing benzalkonium chloride, a preservative not contained in the multidose lidocaine gel. A literature search was performed, using "tetracaine", "tetracaine gel", "lidocaine", "lidocaine gel", "lidocaine jelly", and "cataract surgery" as keywords, and compiling cross-references. A total of 25 studies were identified and included in this review. Of them, seven were uncontrolled studies describing different experiences with the drugs of interest, and 18 were controlled studies. Six studies directly compared tetracaine eye drops or gel with lidocaine gel before cataract surgery. Results: Both tetracaine solution and gel and lidocaine gel proved to be effective in providing analgesia before cataract surgery. Both drugs were comparable with needle injection anesthesia when intracameral lidocaine was added to topical treatment. Direct comparisons indicate better activity for tetracaine when used at the 1% concentration in single-dose units, or in the gel form at a 0.5% concentration. Patients showed a slight preference for the agent that caused the least discomfort when administered (lidocaine), while the surgical complication rate and the surgeon satisfaction were the same with either drug. Conclusion: Tetracaine solution and lidocaine gel were equally effective in providing topical anesthesia for cataract surgery in the published studies. Tetracaine was found to be better than lidocaine only if augmented by either increasing the concentration to 1% (solution) or by increasing the penetration by adding benzalkonium chloride (gel).

This study aims to examine evolving indications and changing trends for corneal transplantation in Italy. Corneal transplantations performed with donor tissues distributed by the Veneto Eye Bank Foundation between 2002 and 2008 were prospectively evaluated. Of the 13,173 keratoplasties performed on 11,337 patients, 10,742 (81.5%) were penetrating (PK), 1644 (12.5%) were anterior lamellar (ALK), and 787 (6.0%) were endothelial (EK). Keratoconus (42.5%), regraft (18.9%), and pseudophakic bullous keratopathy (PBK, 11.9%) were the leading indications for PK, with keratoconus (69.6%) and regraft (6.5%) showing higher indications for ALK, whereas pseudophakic bullous keratopathy (50.1%) and regraft (18.7%) were the major indications for EK. There was an overall decrease observed in corneal grafting for keratoconus (P ¼ .0048) and an increase for PBK (P ¼ .0653) and regrafting (P ¼ .0137). These indications differed by age and gender. The number of keratoplasties over 7 years was stable (P ¼ .2394), although the annual number of PKs declined by 34.0% (P ¼ .0250), ALKs began to rise from 2005 (P ¼ .0600), whereas EKs showed a huge growth, with their number tripling in 2007 and further doubling in 2008 (P ¼ .0004). Leading indications for keratoplasty showed similar data that have been reported elsewhere for Western countries over the past few decades, albeit with a higher percentage of keratoconus. However, the overall number of keratoplasties for keratoconus was in decline, whereas regraft keratopathy and PKs increased due to the application of the newer surgical techniques for corneal grafting. This highlights an important shift in managing corneal diseases toward the application of selective and more conservative surgeries and changes in indications in corneal transplantation.

To investigate the safety and effectiveness of the AcrySof phakic angle-supported intraocular lens (IOL) (Alcon Laboratories, Inc., Fort Worth, TX) for correction of moderate-to-high myopia in adults. Design: One-year interim analysis of a phase 3, nonrandomized, open-label, prospective, multicenter European clinical study. Participants: A total of 190 subjects (190 eyes) with moderate-to-high myopia. The preoperative mean manifest refraction spherical equivalent (MRSE) was Ϫ10.38 diopters (D) Ϯ2.43 standard deviation (SD). Methods: Unilateral implantation of the AcrySof phakic angle-supported IOL. Main Outcome Measures: Best spectacle-corrected visual acuity (BSCVA), uncorrected distance visual acuity (UCVA), predictability and stability of MRSE, adverse events, and endothelial cell density. Results: Of 190 subjects enrolled, 161 completed the 1-year postoperative visit. No subjects lost Ն2 lines BSCVA. A UCVA of 20/20 or better was achieved by 57.8%; 99.4% had 20/40 or better. A BSCVA of 20/32 or better was achieved by 100% of subjects; 85.7% had 20/20 or better. The mean MRSE was Ϫ0.23 D (Ϯ0.50 D: Ϫ2.50 to 0.75 D). Residual refractive error was within Ϯ1.0 D from the target for 95.7% of subjects and within Ϯ0.5 D for 72.7% of subjects. The overall mean percentage change in central endothelial cell density 1 year after surgery was Ϫ4.77Ϯ8.04% (n ϭ 139). No pupil ovalization, pupillary block, or retinal detachment events were observed. Conclusions: The AcrySof phakic angle-supported IOL yielded excellent refractive correction and predictability with acceptable safety in subjects with moderate-to-high myopia. These 1-year interim analysis findings demonstrate preliminary support for the safety and efficacy of this IOL. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Матеріали статті звертають увагу що порушення метаболічних процесів в організмі тварин призводить до зменшення їх продуктивності, втрати якості продукції отриманої від них. Дані, які наведені у статті базуються на дослідженні амінокислотного складу та жиророзчинних вітамінів «А» і «Є» «Д» та водорозчинних «В2» та «С» у молоці корів уражених кетозом. Дослідження проводилось у акредитованій лабораторії. Отримані результати дослідження показують, що при порушенні раціону тварин та незадовільному добробуті, особливо у перші дні після у тварин розвивається від’ємний енергетичний баланс. Це призводить до використання жирових запасів власного тіла і як наслідок утворення значної кількості кетонових тіл з яким печінка нездатна справитися частина із них потрапляє у кров’яне русло що і призводить до отруєння всього організму. Дослідження показують що у молоці корів достовірно (р-≤0,01) збільшується вміст вітаміну «А» та є тенденція до збільшення вмісту вітаміну «Є». Разом із тим вміст вітамін...

Synaptic and axonal glutamatergic signaling to NG2 glia in white matter is critical for the cells' differentiation and activity dependent myelination. However, in gray matter the impact of neuron-to-NG2 glia signaling is still elusive, because most of these cells keep their non-myelinating phenotype throughout live. Early in postnatal development, hippocampal NG2 glia express AMPA receptors with a significant Ca 2+ permeability allowing for plasticity of the neuron-glia synapses, but whether this property changes by adulthood is not known. Moreover, it is unclear whether NG2 glia express auxiliary transmembrane AMPA receptor related proteins (TARPs), which modify AMPA receptor properties, including their Ca 2+ permeability. Through combined molecular and functional analyses, here we show that hippocampal NG2 glia abundantly express TARPs γ4, γ7, and γ8 as well as cornichon (CNIH)-2. TARP γ8 undergoes profound downregulation during development. Receptors of adult NG2 glia showed an increased sensitivity to blockers of Ca 2+ permeable AMPA receptors, but this increase mainly concerned receptors located close to the soma. Evoked synaptic currents of NG2 glia were also sensitive to blockers of Ca 2+ permeable AMPA receptors. The presence of AMPA receptors with varying Ca 2+ permeability during postnatal maturation may be important for the cells' ability to sense and respond to local glutamatergic activity and for regulating process motility, differentiation, and proliferation.

Highlights d In the thalamus, astrocytes and oligodendrocytes form large coupled networks d These panglial networks are essential for energy supply to neurons d Oligodendrocytes assist astrocytes in metabolite transfer to postsynapses Authors

P2X receptors are ligand-gated ion channels which are activated by excitatory neurotransmitter ATP. Despite considerable evidence of signaling by extracellular nucleotides in other sensory systems, P2X receptors in the visual system have only rarely been studied, and almost nothing is known about their functional significance in the retina. To determine whether ATP plays a role in the modulation of vertical retinal signal pathways, we examined the expression of P2X receptor mRNA in freshly isolated bipolar cells of the rat retina Ž . Brown Norway, P25 using the single-cell RT-PCR technique. Positive amplification signals were found in about 33% of the bipolar cells for P2X , P2X and P2X but not for P2X mRNA. We conclude that at least a subpopulation of bipolar cells in the rat retina 3 4 5 7 expresses ionotropic P2 receptors of the P2X type and that these possibly exert a neuromodulatory influence on information processing in the retina.

Since animal models are inevitable for medical research, information on species differences in glial cell properties is critical for successful translational research. Here, we review current knowledge about morphological and functional properties of human astrocytes and NG2 glial cells and compare these data with those obtained for the comparable cells in rodents. Morphological analyses of astrocytes in the neocortex of rodents versus humans have demonstrated clear differences. In contrast, the functional properties of astrocytes or NG2 glial cells in these species are surprisingly similar. However, these findings should be interpreted with caution, as so far functional analyses of human cells are only available from neocortex and hippocampus, and it is known from rodent studies that the properties of astrocytes in different brain regions may vary considerably. Moreover, technical challenges render astrocyte electrophysiological measurements in situ unreliable, and human cell properties may be affected by medications. Nevertheless, based on the limited data currently available, there is substantial similarity between human and rodent astrocytes with regard to those functional properties studied to date. The unique morphological characteristics of astrocytes in human neocortex call for further physiological analysis. The basic properties for NG2 glia are even less completely evaluated with regard to the question of species differences but no glaring differences have been reported so far. In conclusion, it remains justifiable to employ mouse or rat models to investigate the etiology of human CNS diseases that might involve astrocytes or NG2 glia.

NG2 cells are equipped with transmitter receptors and receive direct synaptic input from glutamatergic and GABAergic neurons. The functional impact of these neuron-glia synapses is still unclear. Here, we combined functional and molecular techniques to analyze properties of GABA A receptors in NG2 cells of the juvenile mouse hippocampus. GABA activated slowly desensitizing responses in NG2 cells, which were mimicked by muscimol and inhibited by bicuculline. To elucidate the subunit composition of the receptors we tested its pharmacological properties. Coapplication of pentobarbital, benzodiazepines, and zolpidem all significantly increased the GABA-evoked responses. The presence of small tonic currents indicated the presence of extrasynaptic GABA A receptors. To further analyze the subunit expression, single cell transcript analysis was performed subsequent to functional characterization of NG2 cells. The subunits ␣1, ␣2, ␤3, ␥1, and ␥2 were most abundantly expressed, matching properties resulting from pharmacological characterization. Importantly, lack of the ␥2-subunit conferred a high Zn 2ϩ sensitivity to the GABA A receptors of NG2 cells. Judging from the zolpidem sensitivity, postsynaptic GABA A receptors in NG2 cells contain the ␥2-subunit, in contrast to extrasynaptic receptors, which were not modulated by zolpidem. To determine the effect of GABA A receptor activation on membrane potential, perforated patch recordings were obtained from NG2 cells. In the current-clamp mode, GABA depolarized the cells to approximately Ϫ30 mV, indicating a higher intracellular Cl Ϫ concentration (ϳ50 mM) than previously reported. GABA-induced depolarization in NG2 cells might trigger Ca 2ϩ influx through voltage-activated Ca 2ϩ channels.

P2X receptors are ligand-gated ion channels activated by adenosine triphosphate and expressed in a broad variety of tissues. The present study demonstrates the expression of various types of purinergic P2X receptors in identified retinal ganglion cells (RGCs) of the adult rat retina. Single-cell reverse transcription polymerase chain reaction (SC-RT-PCR) resulted in a positive amplification signal for all P2X receptor subunit mRNAs examined (P2X , P2X ). Immunohistochemistry with P2X receptor subunit-specific antibodies showed 3 -5 7 3,4 a labelling of neurons in the ganglion cell layer and inner nuclear layer. Our data suggest that extracellular ATP acts directly on RGCs via several types of P2X receptors and may provide neuromodulatory influences on information processing in the retina.

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P2X receptors are ligand-gated ion channels activated by ATP. They are expressed in a broad variety of tissues. To date, eight P2X Ž . receptor subunits P2X -P2X , P2XM have been cloned. In spite of the considerable evidence of signaling by extracellular nucleotides 1 7 in other sensory systems, only few studies have been undertaken in the retina. In earlier studies, we have demonstrated that there is mRNA expression of the P2X and P2X subunits in the rat retina. In the present study, molecular biological methods were used to 2 -5 7 Ž . Ž . investigate expression of P2X receptor mRNA in freshly isolated Muller cells MCs of the adult rat retina Brown Norway . A total of 36 MCs was analyzed, employing the single-cell RT-PCR. A positive amplification signal of 11r14 for P2X -mRNA, 5r10 for 3 P2X -mRNA, 3r10 for P2X -mRNA and 0r8 for P2X -mRNA was revealed. Additionally, the astroglial identity of the cells under 4 5 7 Ž . studied was confirmed in 10 cases by simultaneous amplification of RT-PCR products of glutamine synthetase GS -and P2X-mRNA. We conclude that MCs of rat retina express ionotropic P2 receptors, which, in addition to other functions, may play a key role within the recently described long range calcium signaling and the fast direct glia-neuron interactions in the rat retina.

Astrocytes and oligodendrocytes in different brain regions form panglial networks and the topography of such networks can correlate with neuronal topography and function. Astrocyte-oligodendrocyte networks in the lateral superior olive (LSO)-an auditory brainstem nucleus-were found to be anisotropic with a preferred orientation orthogonally to the tonotopic axis. We hypothesized that such a specialization might be present in other tonotopically organized brainstem nuclei, too. Thus, we analyzed gap junctional coupling in the center of the inferior colliculus (IC)-another nucleus of the auditory brainstem that exhibits tonotopic organization. In acute brainstem slices obtained from mice, IC networks were traced employing whole-cell patch-clamp recordings of single sulforhodamine (SR) 101-identified astrocytes and concomitant intracellular loading of the gap junction-permeable tracer neurobiotin. The majority of dye-coupled networks exhibited an oval topography, which was preferentially oriented orthogonal to the tonotopic axis. Astrocyte processes showed preferentially the same orientation indicating a correlation between astrocyte and network topography. In addition to SR101-positive astrocytes, IC networks contained oligodendrocytes. Using Na + imaging, we analyzed the capability of IC networks to redistribute small ions. Na + bi-directionally diffused between SR101-positive astrocytes and SR101-negative cells-presumably oligodendrocytes-showing the functionality of IC networks. Taken together, our results demonstrate that IC astrocytes and IC oligodendrocytes form functional anisotropic panglial networks that are preferentially oriented orthogonal to the tonotopic axis. Thus, our data indicate that the topographic specialization of glial networks seen in IC and LSO might be a general feature of tonotopically organized auditory brainstem nuclei.

Extracellular purines are important signaling molecules involved in numerous physiological and pathological processes via the activation of P2 receptors. Information about the spatial and temporal P2 receptor (P2R) expression and its regulation remains crucial for the understanding of the role of P2Rs in health and disease. To identify cells carrying P2X2Rs in situ, we have generated BAC transgenic mice that express the P2X2R subunits as fluorescent fusion protein (P2X2-TagRFP). In addition, we generated a BAC P2Y1R TagRFP reporter mouse expressing a TagRFP reporter for the P2RY1 gene expression. We demonstrate expression of the P2X2R in a subset of DRG neurons, the brain stem, the hippocampus, as well as on Purkinje neurons of the cerebellum. However, the weak fluorescence intensity in our P2X2R-TagRFP mouse precluded tracking of living cells. Our P2Y1R reporter mice confirmed the widespread expression of the P2RY1 gene in the CNS and indicate for the first time P2RY1 gene expressi...

Retinal fundus images play an important role in the diagnosis of Diabetic Retinopathy. The detailed information of retinal images like Retinal Vessels, Exudates and microaneurysms may be in low contrast and retinal image enhancement helps in the accurate diagnosis of retinal images related diseases. This paper proposes a novel contrast enhancement method to make the low-contrast retinal images more qualitative such that the detailed information will be clearer. For this purpose, the proposed mechanism considers the spatial mutual relationships between the gray-levels of image and makes the gray-levels in the output image not only linear to the gray-levels of input image but also related to the neighboring gray-levels. The proposed approach enhances the image both in global and local fashion. Spatial mutual entropy based contrast enhancement is accomplished for global contrast enhancement and Greedy contrast enhancement is accomplished for local contrast enhancement. Extensive simulations carried out over various low-contrast retinal images of High Resolution Fundus (HRF) image database shows the outstanding performance of proposed approach. And, different from some other fundus image enhancement methods, the proposed method can directly enhance color images.

Current approaches to monitor and quantify cell division in live cells, and reliably distinguish between acytokinesis and endoreduplication, are limited and complicate determination of stem cell pool identities. Here we overcome these limitations by generating an in vivo reporter system using the scaffolding protein anillin fused to enhanced green fluorescent protein, to provide high spatiotemporal resolution of mitotic phase. This approach visualizes cytokinesis and midbody formation as hallmarks of expansion of stem and somatic cells, and enables distinction from cell cycle variations. High-resolution microscopy in embryonic heart and brain tissues of enhanced green fluorescent protein-anillin transgenic mice allows live monitoring of cell division and quantitation of cell cycle kinetics. Analysis of cell division in hearts post injury shows that border zone cardiomyocytes in the infarct respond with increasing ploidy, but not cell division. Thus, the enhanced green fluorescent protein-anillin system enables monitoring and measurement of cell division in vivo and markedly simplifies in vitro analysis in fixed cells.

Equisetum hyemale species is considered a medicinal plant used in the form of infusions to combat infectious or inflammation diseases and also diuretic effects, presenting several compounds related to these actions. In previous studies different species of Equisetum showed several phenolic compounds. The objective of this study was, for the first time, based on phytochemistry analysis to evaluate the antioxidant and antimicrobial activity. The 70% ethanolic and methanolic extracts of E. hyemale were characterized by spectrophotometric and high-performance liquid chromatography with pulsed amperometric detector analyses, as well as its antioxidant potential based on the scavenger activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH). In addition was verified the antimicrobial activity by broth microdilution technique against bacteria and fungi. The extracts showed phytochemical similarity, which demonstrated the presence of phenolic compounds, the scavenging activity for free radicals was about 30% and was observed better antifungal activity against dermatophyte fungi, with minimum inhibitory concentration and minimum fungicidal concentration of 0.62 mg/mL to Trichophyton rubrum and Microsporum canis. The extracts exhibits great potential to therapeutic applications or product development, since both possess antifungal activity and antioxidant action associated with little difference in their phytochemical composition.

Energy consumption constraints on computing systems are more important than ever. Maintenance costs for high performance systems are limiting the applicability of processing devices with large dissipation power. New solutions are needed to increase both the computation capability and the power efficiency. Moreover, energy efficient applications should balance performance vs. consumption. Therefore power data of components are important. This work presents the most remarkable alternatives to measure the power consumption of different types of computing systems, describing the advantages and limitations of available power measurement systems. Finally, a methodology is proposed to select the right power consumption measurement system taking into account precision of the measure, scalability and controllability of the acquisition system.