Epigenetic and Posttranscriptional Regulation in Retinoblastoma

The Retinoblastoma 1 (RB1) gene, located on chromosome 13q14 and encodes the tumor-suppressor retinoblastoma protein, is the cause of Retinoblastoma. The mutational inactivation of both gene alleles brings on this cancer. Retinoblastoma (RB) high-risk histopathological characteristics indicate metastasis or local recurrence with rapid progresses following RB1 inactivation. There is growing interest in regulatory activities unconnected to the coding region of the genome, or exome, in addition to epigenetic control mechanisms. The altered epigenome is significant, though by no means the only, problem in the etiology of Retinoblastoma. After all, cancer development is a multistep process in which numerous dissimilar genetic, epigenetic, and posttranscriptional modifications result in a shared phenotype. This study emphasizes the most recent developments in posttranscriptional change and epigenetics related to retinoblastoma tumor biology. Here, we highlight the novel biomarkers the retinoblastoma tumor has expressed to improve patient survival.

Biological Corridors as a Connectivity Tool in the Region of the Great American Chaco:Identification of Biodiversity Hotspots in the Ecoregions of the Paraguayan Chaco

This work presents the main biodiversity hotspots existing in the Paraguayan Chaco and is an update of the results obtained in the first Ecoregional Assessment of the Great American Chaco.These are the results of a series of workshops that included scientific and technical discussions carried out by local experts in zoology,botany,forestry,soil science,and hydrogeology applying a biodiversity vision of 25-30 years for the territory,after overlapping the maps of the first assessment with that of the advance of the changes of land use in the territory.Criteria for detecting biodiversity hotspots were discussed,including:permanent and temporary watercourses,other bodies of water such as fresh and salty lagoons,reserve areas of different categories,as well as important bird areas(IBAs),RAMSAR areas and others,which must be connected in the future,combining the production areas with the conservation of biodiversity.

Outcomes after combined excisional goniotomy and manual small incision cataract surgery

AIM: To report the long-term outcomes of combined excisional goniotomy and manual small incision cataract surgery(MSICS).METHODS: This is a retrospective case series of patients with open angle glaucoma and visually significant cataracts that underwent combined excisional goniotomy and MSICS with one-year follow-up. The medical history, demographic information, and clinical characteristics of each case were recorded. Data regarding changes in vision, intraocular pressure(IOP), the number of glaucoma medications, and the evolution of the disease after surgery were reported. RESULTS: Three patients, with open angle glaucoma and cataracts underwent combined excisional goniotomy and MSICS without adverse events. All patients had improvement in vision compared to baseline measurements. The range of IOP at baseline was from 14 to 18 mm Hg and decrease to a range of 10 to 14 mm Hg after one year of follow-up. Additionally, two patients also decreased their dependence on IOP-lowering medications at the last follow up visit with one patient maintaining baseline level of medication use.CONCLUSION: A combination of excisional goniotomy and MSICS illustrates both the safety and efficacy to treat patients with visually significant cataract and glaucoma. This procedure allows for a more cost-effective surgical approach that matches the needs of resource strained territories around the globe.

The effect of transcorneal electrical stimulation in visual acuity: Retinitis pigmentosa

Transcorneal Electrical Stimulation (TES) was applied to a group of volunteer patients suffering from Retinitis Pigmentosa (RP), in order to investigate the effect of TES in Visual Acuity (VA). 28 partial blind patients with diagnosis of classic RP, Usher syndrome I and/or II were stimulated transcornealy, during a period of 52 weeks using a non conventional waveform, only in the lowest visually capable eye. The proposed waveform has been modeled from the natural response of human retina and delivered by means of an adaptive generator designed and built for tissue stimulation. Statistical results show the improvement of average VA or at least the contention of the disease natural progress. Categorized analysis of results indicates the same effect that if the age of patients, time since diagnosis and genetic disorder variation (classic RP, Usher syndrome I and/or II) are considered, in this case clinical and electrophysiological follow-up parameters were statistically analyzed in order to know the effect of TES. General results yield an improvement of 48.15% in the average of VA for stimulated eyes against an average degreasing of -8.06% in the same scale, with respect to their basal condition before the start of the experiment.

Weighing of risk factors for penetrating keratoplasty graft failure：application of Risk Score System

AIM：To analyze the relationship between the score obtained in the Risk Score System（RSS）proposed by Hicks et al with penetrating keratoplasty（PKP）graft failure at 1y postoperatively and among each factor in the RSS with the risk of PKP graft failure using univariate and multivariate analysis.METHODS：The retrospective cohort study had 152 PKPs from 152 patients. Eighteen cases were excluded from our study due to primary failure（10 cases）,incomplete medical notes（5 cases）and follow-up less than 1y（3cases）. We included 134 PKPs from 134 patients stratified by preoperative risk score. Spearman coefficient was calculated for the relationship between the score obtained and risk of failure at 1y. Univariate and multivariate analysis were calculated for the impact of every single risk factor included in the RSS over graft failure at 1y. RESULTS：Spearman coefficient showed statistically significant correlation between the score in the RSS and graft failure（P〈0.05）. Multivariate logistic regression analysis showed no statistically significant relationship（P〉0.05）between diagnosis and lens status with graft failure. The relationship between the other risk factors studied and graft failure was significant（P〈0.05）,although the results for previous grafts and graft failure was unreliable. None of our patients had previous blood transfusion,thus,it had no impact. CONCLUSION：After the application of multivariate analysis techniques,some risk factors do not show the expected impact over graft failure at 1y.

Analyzing the genomic and transcriptomic architecture of milk traits in Murciano-Granadina goats

Background:In this study,we aimed to investigate the molecular basis of lactation as well as to identify the genetic factors that influence milk yield and composition in goats.To achieve these two goals,we have analyzed how the mRNA profile of the mammary gland changes in seven Murciano-Granadina goats at each of three different time points,i.e.78 d(T1,early lactation),216 d(T2,late lactation)and 285 d(T3,dry period)after parturition.Moreover,we have performed a genome-wide association study(GWAS)for seven dairy traits recorded in the 1st lactation of 822 Murciano-Granadina goats.Results:The expression profiles of the mammary gland in the early(T1)and late(T2)lactation were quite similar(42 differentially expressed genes),while strong transcriptomic differences(more than one thousand differentially expressed genes)were observed between the lactating(T1/T2)and non-lactating(T3)mammary glands.A large number of differentially expressed genes were involved in pathways related with the biosynthesis of amino acids,cholesterol,triglycerides and steroids as well as with glycerophospholipid metabolism,adipocytokine signaling,lipid binding,regulation of ion transmembrane transport,calcium ion binding,metalloendopeptidase activity and complement and coagulation cascades.With regard to the second goal of the study,the performance of the GWAS allowed us to detect 24 quantitative trait loci(QTLs),including three genome-wide significant associations:QTL1(chromosome 2,130.72-131.01 Mb)for lactose percentage,QTL6(chromosome 6,78.90-93.48 Mb)for protein percentage and QTL17(chromosome 17,11.20 Mb)for both protein and dry matter percentages.Interestingly,QTL6 shows positional coincidence with the casein genes,which encode 80%of milk proteins.Conclusions:The abrogation of lactation involves dramatic changes in the expression of genes participating in a broad array of physiological processes such as protein,lipid and carbohydrate metabolism,calcium homeostasis,cell death and tissue remodeling,as well as immunity.We also conclude that genetic variation at the casein genes has a major impact on the milk protein content of Murciano-Granadina goats.

Sensitivity of X-Band (σ0, γ) and Optical (NDVI) Satellite Data to Corn Biophysical Parameters

The objective of this work was to evaluate the sensitivity of three different satellite signals (interferometric coherence (γ), backscattering coefficient (σ0) and NDVI) to corn biophysical parameters (leaf area index, height, biomass and water content) throughout its entire vegetation cycle. All of the satellite and in situ data were collected during the Multi-spectral Crop Monitoring (MCM’10) experiment conducted in 2010 by the CESBIO Laboratory over eight different agricultural sites located in southwestern France. The results demonstrated that the NDVI is well adapted for leaf area index monitoring, whereas γ27.3° is much more suited to the estimation of the three other Biophysical Parameters throughout the entire crop cycle, with a coefficient of determination ranging from 0.83 to 0.99, using non-linear relationships. Moreover, contrary to the use of the NDVI or backscattering coefficients, the use of coherence exhibited a low sensitivity to the changes in vegetation and soil moisture occurring during senescence, offering interesting perspectives in the domain of applied remote sensing

Intravitreal Bevacizumab for the Treatment of Chronic or Recurrent Central Serous Chorioretinopathy

Background: We report the use of intravitreal bevacizumab as an option for the treatment of chronic or recurrent central serous chorioretinopathy (CSC). Methods: Eight eyes with chronic or recurrent CSC received intravitreal bevacizumab (1.25 mg/0.05 cc) and underwent best corrected visual acuity (VA), optical coherent tomography (OCT), fluorescein angiography (FA) and indocyanine green angiography (ICG) before, and one, three and six months after treatment. Results: All patients showed improvement in visual acuity, fluorescein angiographic leakage, choroidal hyperpermeability and reduced or resolved neurosensory detachment following treatment. Two patients require a second dose of intravitreal bevacizumab. Conclusions: Intravitreal injection of bevacizumab was associated with visual improvement and reduced neurosensory detachment without adverse events in patients with chronic or recurrent CSC. Although these results are promising, further investigations would be helpful to understand this therapy for patients with CSC.

Proposed Protocol for Risk Assessment and Stratification

Introduction: COVID-19 disease is a highly contagious viral infection caused by the SARS-CoV-2 coronavirus. There is growing interest in Public Health and Occupational Health in identifying the COVID-19 prognostic factors, needed to stratified patients by risk being necessary to consider occupational variables as well as individual and clinical factors of the workers. Objective: The aim of this study was to perform a tool to identify the more vulnerable workers for COVID-19 that will be useful to value their work limitations. Methods: A review of medical literature about the vulnerability for COVID-19 is taken into account occupational risks and occupational preventive measures. Results: It is proposed an index of vulnerability criteria for COVID-19 in workers based on quantifying individual characteristics, pre-existing medical conditions and its control, high risk of occupational exposure, and prevention and protection strategies in the workplace. The final result is stratified into three degrees of vulnerability that will serve to propose the most appropriate preventive measures. Conclusion: This proposal protocol assesses about the vulnerability for COVID-19 infection in workers to help decide the preventive management at workplace in this pandemic situation.

Interferon-free treatments in patients with hepatitis C genotype 1-4 infections in a real-world setting

AIM To investigated the real-world effectiveness and safety of various regimens of interferon-free treatments in patients infected with hepatitis C virus(HCV).METHODS We performed an observational study to analyze different antiviral treatments administered to 462 HCV-infected patients, of which 56.7% had liver cirrhosis. HCV RNA after 4 wk of treatment and at 12 wk after treatment sustained virologic response(SVR) as well as serious adverse events(SAEs) was analyzed first for the whole cohort and then separately in patients who met or did not meet the inclusion criteria of a clinical trial(CT-met and CT-unmet, respectively).RESULTS The most frequently prescribed treatment was simeprevir/sofosbuvir(36.4%), followed by sofosbuvir/ledipasvir(24.9%) and ombitasvir/paritaprevir/ritonavir(r)/dasabuvir(19.9%). Ribavirin(RBV) was administered in 198 patients(42.9%). SVRs occurred in 437/462 patients(94.6%). The SVRs ranged between 93.3% and 100% for genotypes 1-4. SVRs were achieved in 96.2% patients in the CTmet group vs 91.9% patients in the CT-unmet group(P = 0.049). Undetectable HCV RNA at week 4 occurred in 72.9% of the patients. In the univariate analysis, the factors associated with SVRs were lower liver stiffness, absence of cirrhosis, higher platelet count, higher albumin levels, no RBV dose reduction, undetectable HCV RNA at week 4 and CT-met group. In the multivariate analysis, only albumin was an independent predictor of treatment failure(P = 0.04). Eleven patients(2.4%) developed SAEs; 5.2% and 0.7% of the patients in the CT-unmet and CT-met groups, respectively(P = 0.003).CONCLUSION A high proportion of patients with HCV infection achieved SVRs. For patients who did not meet the CT criteria, treatment regimens must be optimized.

Proposed Occupational Vulnerability Index COVID-19

Introduction: Vulnerable is someone who can be hurt or receive injury, physically or morally. The work environment appears as one of the dimensions in which social vulnerability develops and social and occupational vulnerability is defined. The literature does not include an assessment of quantified occupational vulnerability as it already exists in the case of social vulnerability. The aim of this paper is to identify and quantify the variables included in the Protocol for the Assessment of Vulnerability to COVID-19 in such a way that the result can be quantified and allows for a predictive effect on the degree of vulnerability. Methodology: The starting point is the design of a protocol proposal that includes 29 variables. Data is collected from a sample of 420 workers, quantifying the results according to each variable, the overall scores for each group of aspects assessed and, finally, the total score that estimates the degree of vulnerability according to established ranges. Results: Variables that have the highest coefficient and, therefore, the greatest weight in the probability of reaching a group of high or medium vulnerability are cardiovascular disease, cancer, and coagulation alteration. The weight of the labour aspects due to inadequate working conditions stands out. Conclusions: The results obtained with this protocol allow us to make a quantified assessment of labour vulnerability to COVID-19 by integrating individual variables of the worker, his working conditions and the preventive actions of his company against COVID-19, and can be useful as an Occupational Vulnerability Index (OVI).

Flexible Polyimide Microelectrodes Array for Transcorneal Electrical Stimulation

The relationship between the parameters of Transcorneal Electrical Stimulation (TES) and its neuro-protective effect of TES on axotomised Retinal Ganglion Cells (RGCs) is still unclear. This work discusses the design strategy of a new non conventional TES stimulator, the micro fabrication processes and characterization of an array of MEMS microelectrodes over a flexible polymer layer substrate to stimulate the human cornea. The micro-array of electrodes, over a flexible smooth biocompatible polyimide substrate, fine tunes the curvature of the cornea. This tool can help researchers to define the optimal electric stimulation parameters required in TES.

Inhaler Technique Questionnaire(InTeQ)in pediatric patients with asthma

Asthma in school-aged children is a major public health problem worldwide[1,2].Inhaled medications are the mainstay of its pharmacological management[2],but only 8%-22%of children with asthma use their inhalers correctly[3].Asthma clinical outcomes are poor in children[4],largely due to inhaler technique[5,6].

Sensitivity,specificity and predictive values of anterior chamber tap in cases of bacterial endophthalmitis

Background:To assess the sensitivity,specificity,positive predictive value and negative predictive value of anterior chamber tap for the diagnosis of bacterial endophthalmitis on a population with high prevalence.Methods:Retrospective,single centre,case series study.We reviewed all medical records with clinical diagnosis of bacterial endophthalmitis in our hospital from January 1st,2000 to December 31st 2014.From each record,we documented general demographic data,best corrected visual acuity and vitreous and aqueous tap microbiological results.All cases were further divided according to the endophthalmitis aetiology to perform individual calculations of sensitivity,specificity,positive predictive value,negative predictive value,accuracy and prevalence.We used the results of the vitreous tap as the gold standard for diagnosis of bacterial endophthalmitis.We excluded those records in which the aqueous and vitreous samples were not taken simultaneously or had an incomplete microbiological report.Significance were assessed with chi squared statistics,with an alpha value of 0.05 for statistical significance.Results:A total of 190 cases fulfilled the inclusion/exclusion criteria.Positive culture rate from vitreous samples was 64.74%.Positive culture rate from aqueous sample was 32.11%.Bacteria isolated from aqueous samples matched those isolated from vitreous samples 78.68%of the time.The overall sensitivity was 38.21%,specificity:75.51%,positive predictive value:79.66%,negative predictive value:32.74%(p=0.08).Subgroup analysis showed that anterior chamber taps in cases of post-surgical endophthalmitis had a moderate to low sensitivity(37.73%),high specificity(93%)and high positive predictive value(95%)(p<0.04).Conclusion:The sensitivity and specificity of anterior chamber tap are low and should not be used for critical therapeutic decisions in patients with suspected bacterial endophthalmitis.In cases of post-surgical endophthalmitis,the result of an anterior chamber tap could be used for therapeutic guidance,but only in conjunction with clinical presentation and in the absence of a better method for diagnosis.

The value of the World Conferences on Research Integrity:perspectives from Peru

“The World Conferences on Research Integrity(WCRIs),six to date,were initiated at a time when researchers in various countries were at quite different stages in their thinking about research integrity.Over the course of the past decade,the global conferences have reflected and documented significant changes in the way research integrity is viewed and supported”[1].

Projected effectiveness of HIV detection during early infection and rapid ART initiation among MSM and transgender women in Peru: A modeling study

Background:The Sabes study,a treatment as prevention intervention in Peru,tested the hypothesis that initiating antiretroviral therapy(ART)early in HIV infection when viral load is high,would markedly reduce onward HIV transmission among high-risk men who have sex with men(MSM)and transgender women(TW).We investigated the potential population-level benefits of detection of HIV early after acquisition and rapid initiation of ART.Methods:We designed a transmission dynamic model to simulate the HIV epidemic among MSM and TW in Peru,calibrated to data on HIV prevalence and ART coverage from 2004 to 2011.We assessed the impact of an intervention starting in 2018 in which up to 50%of the new infections were diagnosed within three months of acquisition and initiated on ART within 1 month of diagnosis.We estimated the impact of the intervention over 20 years using the cumulative prevented fraction of new HIV infections compared to scenarios without intervention.Findings:Our model suggests that only 19%of the infected MSM and TW are virally suppressed in 2018 and 35%e40%of the new HIV infections are transmitted from contacts with acutely-infected partners.An intervention reaching 10%of all acutely infected MSM and TW is projected to prevent 13.3%[Uncertainty interval:11.9%e14.3%]of the new infections over 20 years and reduce HIV incidence in 2038 by 24%.Reaching 50%of all acutely infected MSM and TWwill increase the prevalence of viral suppression in 2038 to 59%and prevent 41%of expected infections over 20 years.Reaching 50%of the high-risk MSM and TW in acute phase would reduce HIV incidence in 2038 by 60%and prevent 36%of new infections between 2018 and 2038.Conclusions:Early detection of HIV infections and rapid initiation of ART among MSM is desirable as it would increase the effectiveness of the HIV prevention program in Peru.Targeting high-risk MSM and TW will be highly efficient.

野外农场工作站:一个新的农业生态试验点的空间结构

Dehesa生态系统对整个伊比利亚半岛有着重要的社会和经济价值。在气候变化下评估该系统的时间动态对于维护和保护这些极具价值的生态系统非常重要。本论文展示了Dehesa生态系统一个观测样点的基础数据,这些数据为在Dehesa生态系统内进行长期动态监测,以及开展检验森林恢复力驱动机制的实验模拟奠定了基础。初步调查表明,Dehesa的森林结构是典型的,说明其是研究该生态系统时间动态的典型样地。我们展示这些基础数据是为了鼓励国际科学家通过直接实验项目或meta分析进行合作。

Using detection dogs and genetic analyses of scat to expand knowledge and assist felid conservation in Misiones, Argentina

Many carnivores require large ranges to meet their ecological and energetic needs;however,anthropogen­ic changes threaten species and their habitats.Camera traps have been used to effectively collect data on car­nivores in a variety of habitat types;however,a single survey effort is typically limited to species that have similar body size,habitat use and movement patterns,and individual identification of animals is not always pos­sible.We evaluated whether scat detection dogs could effectively survey for 4 wide-ranging felids that vary in these characteristics:jaguars(Panthera onca),pumas(Puma concolor),ocelots(Leopardus pardalis)and oncil­las(Leopardus tigrinus).From June to October 2009 and May to August 2011,a detection dog-handler team de­tected 588 scats,from which 176 unique genotypes were detected.We assigned sex to 84.7%of the genotyped scats and identified 55 individuals multiple times.The effectiveness of these noninvasive techniques(detection dogs and genetic analyses of scat)not only opens the door for additional studies in areas that were previous­ly difficult or impossible with standard survey techniques,but also provides conservationists with a set of tools that overcome some of the limitations associated with the use of camera traps alone.