COVID-19 is the global-pandemic targets human-lung-ACE2 that converts Angiotensin-II to (1-7) peptide causing vasodilatation. Vasoconstriction caused by Angiotensin-II is produced from Angiotensin-I by ACE1. The vaso-status maintains blood-pressure/vascular-health of the individuals which is demolished in Covid-19 infection manifesting aldosterone/salt-deregulations/inflammations/endothelial-dysfunctions/hyper-hypo- tension, sepsis/hypovolemic-shock and vessel-thrombosis/coagulations. These cause comorbidity patients. Here, nigellidine, an indazole-alkaloid was analyzed by molecular-docking for binding to different Angiotensin-binding-proteins (enzymes, ACE1(6en5)/ACE2(4aph)/receptors, AT1(6os1)/AT2(5xjm)) and COVID-19 spike-glycoprotein(6vsb). Data suggest that nigellidine strongly binds to the spike-protein at the hinge-region/active-site-opening which may hamper proper-binding of nCoV2-ACE2 surface. Nigellidine strongly (-7.54 kcal/mol, -211.76, Atomic-Contact-Energy; ACE-value) binds (>known-binderEGCG; -4.53 and Theaflavin-di-gallate; -2.85) in the Angiotensin-II binding-site/entry-pocket at ACE2 with Ki 8.68 and 8.3 µmol. Further, Nigellidine showed strong-binding (best Ki, 50.93µmol/binding-energy -5.48 kcal/mol) to both mono- and multi-meric ACE1-forms. Moreover, this compound binds Angiotensin-receptors, AT1/AT2 (Ki, 42.79/14.22 µmol, binding-energy, -5.96/-6.61 kcal/mol) at active-sites, respectively. Here, we first-time report that nigellidine can block all angiotensin-binding proteins where, the Angiotensin-bonded amino acids were more or less similar/analogous and effectively blocked by nigellidine. The ACEs-blocking could restore Angiotensin-level and restrict vaso-turbulence in Covid-infected patients and receptor-blocking might stop inflammatory/vascular impairment. Further, nigellidine may slowdown the vaso-fluctuations due to Angiotensin deregulations in Covid-infected patients. Angiotensin II-ACE2 binding (ACE-value -294.81) is more favorable than nigellidine-ACE2. Contrarily, nigellidine-ACE1 binding-energy/Ki are lower than nigellidine-ACE2 values indicating a balanced-state between constriction-dilatation. It is also noticed that nigellidine binds to the viral-spike, closer proximity to its ACE2 binding-domain. Taken together, Covid-infected-patients/elderly-patients/comorbid-patients (with hypertensive/diabetic/cardiac/renal impairment, counting >90% of non-survivors) could be greatly benefited.

Objective: Comparison of birthweight references for diagnosing SGA. To provide denominator data for suspicion and diagnosis of SGA. Design: A retrospective cohort study of 10,616 babies. Setting: A regional obstetric centre. Population: 10,616 consecutive newborns, born in Derriford Hospital, University Hospitals Plymouth NHS Trust (UPHT), whilst using the GROW package,1 compared with using Intergrowth 21st (IG21),2 and British 1990 (UK90) references.3 Methods: Statistical analysis of centile data from GROW, IG21 and UK90 references. Main outcomes: Induction rates, detection of suspected and/or diagnosed SGA. Assessment of goodness of fit to the Plymouth population. Results: GROW and IG21 showed bias. GROW had a systematic bias towards smaller centiles (skewness 0.169). IG21 had a systematic bias towards larger centiles (skewness -0.452). UK90 was best fit to the Plymouth dataset with insignificant bias across centiles (skewness -0.047). Conclusions: GROW and IG21 are not appropriate gold standards for our population for allocation of birthweight centile. The size of the population suggests the conclusions may be extrapolatable to other centres. UK90 does not have everyday accessible tools compared with GROW and IG21. A continual local audit of birthweight would be ideal, enabling accurate local centile allocation. If a national SGA screening programme monitoring units’ ability to detect SGA was introduced, it could not start without validated, unit specific birthweight data. Funding: The statistician’s funding was obtained from UHPT Research and Development generic funding.

The ecosystem of tea plantations portrays a special interaction among environment, soil microorganisms and tea trees. Under the influence of environmental factors and human management, the growth, quality, yield of tea trees and the tea leaves may also be dependent upon the changes in the soil microbial community. However, little is known about the composition and structure of soil bacterial and fungal communities in hundred-year-old tea plantations and the mechanisms by which they are affected. In this regard, we characterized the microbiome of tea plantation soils by considering the bacterial and fungal communities in 448 soil samples from 101 ancient tea plantations in eight counties of Lincang city, which is one of domestication centers of tea trees in the world. We applied 16S and ITS rRNA high-throughput sequencing techniques, and found that the effect of pH and altitude changes on the relative abundance of fungal communities was more pronounced than that on bacteria. In terms of the influence of pH and altitude on soil microbial communities, the abundance and diversity of bacterial communities were more sensitive to pH than those of fungi. The α-diversity of bacterial communities peaked in the pH 4.50-5.00 and altitude 2,200 m group, and the highest α-diversity of fungi showed in the pH 5.00-5.50 and 900 m group. While all microbes varied similarly changing with environment and geographies, and further correlations were found that the composition and structure of bacterial communities were more sensitive to latitude and altitude than that of fungal communities.

Background: We developed an integrated triple-branched stent to treat acute DeBakey type I aortic dissection and modified it to enhance its adaptability. However, whether the patients treated by the modified stent would achieve better long-term prognosis is unknown. Methods: This study enrolled 147 patients with acute DeBakey type I aortic dissection. The original integrated triple-branched stents were used in 57 patients (group A) between July 2012 and August 2013, and the modified stents in 90 patients (group B) between September 2013 and March 2015. Clinical characteristics, surgical data, postoperative complications, mortality, and follow-up data of the two groups were analyzed. Results: The two groups presented comparable early death rate (group A=7.0%, group B=5.9%, p=0.719). The incidence of postoperative acute kidney injury was lower in group B (10.0%) vs group A (24.6%) (p=0.018). Compared with the original integrated triple-branched stent graft, the modified stent could reduce the risk of early postoperative acute kidney injury [OR (95%CI)=0.36(0.14, 0.94)]. Early endoleak rate was lower in group B (1.0%) vs group A (9.4%) (p=0.004). During follow-up, there were five deaths in group A (9.4%) and six deaths in group B (7.2%) (p=0.646). Chronic kidney injury (7.5% vs 3.6%, p=0.311), delayed endoleak (11.3% vs 4.8%, p=0.157), and late reinterventions (7.5% vs 2.4%, p=0.155) in the two groups were similar. Conclusions: In patients with acute DeBakey type I aortic dissection, the modified stent could provide feasible and safe treatment outcomes, with better protection of kidney function and reduced early endoleak. However, they had similar long-term effects.

Aims To investigate a modified method of epicardial left atrial appendage (LAA) occlusion under the guidance of thoracoscopy and transesophageal echocardiography (TEE) during radiofrequency ablation of atrial fibrillation. Methods and Results 19 patients with atrial fibrillation underwent left atrial appendage occlusion and atrial fibrillation radiofrequency ablation in two centers under the guidance of thoracoscopy and TEE. All of the surgeries were completed in a general surgery setting, avoiding fluoroscopy, and in each case the entire procedure was guided by TEE. Radiofrequency ablation of atrial fibrillation was performed by Wolf mini-maze. All operations went smoothly with no serious complications. Postoperative TEE indicated that each device was in a good position and there was no residual shunt around any of the devices. Conclusions It is safe and reliable to apply the left atrial appendage closure device to perform epicardial left atrial appendage occlusion guided only by TEE, which is radiation-free. And it can be performed simultaneously during the thoracoscopic radiofrequency ablation of atrial fibrillation.

Background: Whilst core curricula in neurology are nationally standardised, in real-world clinical practice, different approaches may be taken by individual consultants. In this study, we investigated: (1) variance in diagnostic and investigative practice, using a case-based analysis of inter-rater agreement; (2) potential importance of any differences in terms of patient care; (3) relationships between clinical experience, diagnostic certainty, diagnostic peer-agreement and investigative approach; (4) development of novel individualised metrics to facilitate appraisal. Methods: Four neurologists with 0-23 years’ experience at consultant level provided diagnosis, certainty (10-point Likert scale), and investigative approach for 200 consecutive general neurology outpatients seen by a newly qualified consultant. Diagnostic agreement was evaluated by percentage agreement. The potential importance of any diagnostic differences was assigned a score by the evaluating neurologist (6-point Likert scale). Associations between diagnostic agreement, certainty and investigative approach were assessed using Spearman correlation, logistic and ordinal regression, and reported as individualiszd metrics for each rater. Results: Diagnostic peer-agreement was 4/4, 3/4, 2/4 and 1/4 in 50%, 28%, 20% and 3% of cases, respectively. In 17%, differences in patient management were judged potentially important. Investigation rates were 42-73%. Mean diagnostic certainty ranged between 6.2/10 (SD 2.1) to 7.7/10 (SD 2.2) between least and most experienced consultants. Greater diagnostic certainty was associated with greater diagnostic peer-agreement (individual-rater regression coefficients 0.30-0.51, p<0.01) and lower odds of arranging investigations (individual-rater odds ratios 0.58-0.78, p<0.01). Conclusions: Variance in diagnostic and investigative practice between consultant neurologists exits and may result in differing management. Mean diagnostic certainty increased numerically with experience and was statistically associated with greater diagnostic peer-agreement and lower investigation rates. Metrics reflecting concordance with peers, and relationships to diagnostic confidence, could inform reflective practice.

Understanding the molecular basis of stress is of long standing interest in biology and fish science. We tackled this question by modifying the epiGBS (epiGenotyping By sequencing) technique to screen for cytosine methylation and explore the genome-wide epigenomic response to a repeated acute stress challenge in the European sea bass (Dicentrarchus labrax). Following a minimally invasive sampling using nucleated red blood cells (RBCs), our modified epiGBS protocol retrieved 501,108,033 sequencing reads after trimming, with a mean mapping efficiency of 73.0% (unique best hits). Sequencing reads mapped across all linkage groups (LGs). A total of 47,983 CpG coordinates with a minimum 30X read depth was retained for differential methylation analysis between pre- and post-stress fish. A family effect was demonstrated, and 57 distinct differentially methylated cytosines (DMCs) distributed on 17 of 24 LGs were found between RBCs of pre- and post-stress individuals and located close to 51 distinct stress-related genes. Thirty-eight of these genes were previously reported as differentially expressed in the brain of zebrafish, most of them involved in stress coping differences. Some DMC-related genes appear as good candidates to study the stress response, especially a set of them associated to the Brain Derived Neurotrophic Factor (BDNF), a protein that favors stress adaptation and fear memory. Limits to our study and future directions are presented, including the use of RBCs as a surrogate to other target tissues, to provide with classical physiological measurements a more complete picture of the stress response in fish.

Accelerated expansion of the Yan Lake basin since 2010 has been confirmed by dramatic increases in area determined by remote sensing images and measurements of rapid water level rise (2015–2018). However, the underlying causes of this expansion remain unclear. In this study, lake area, water levels, and volume fluctuations were investigated and the water balance reconstructed. The results showed the Lake Yan area, water level, and volume increased to 59.9 km2, 7.91 m, and 14.17 Gt, respectively, by 2018, with 60%–70% of the increase during August to October within 1 yr. Over the past 40 yrs, lake area, level, and volume of lake Yan varied in three stages: slight increase (1980s–2011), rapid increase (2011–2013), and steady increase (2014–2018). A Mann-Kendall analysis suggested that precipitation and air temperature continuously increased at 2.22 mm yr-1 and 0.05°C yr-1, respectively. As for the glacier, meltwater was 1.0±0.2 Gt and accounted for a smaller proportion of the lake water supply. The lake water balance identified increased net precipitation as the dominant factor (71%) for the increase in lake water storage, followed by groundwater (16%) and glacial meltwater (15%). These estimates provide the first quantitative evaluation of the water balance components in the Yan Lake basin, which could provide insights into the responses of Tibetan lake dynamics to climate change.

Dear Editor:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious infectious disease of international concern that spreads mainly from person to person through respiratory droplets.1,2 As of July 2020, outbreaks are being reported in China, the country where the pandemic started and in which it was thought initially to be controlled.3 In a similar manner, in other countries like Peru, instead of being controlled, the pandemic is increasing in severity and prevalence. Until July 6, 2020, > 11 million cases had been confirmed across the world, with > 300 000 cases and > 10 000 deaths in Peru.4It is necessary to adopt intentional and thoughtful acts to control the SARS-CoV-2 pandemic. Social distancing measures, minimization of personal contacts, and hand sanitization are effective in limiting the community spread of SARS-CoV-2.1 However, there are social variables that cannot be controlled in Peru, such as lower level education and poor socioeconomic status in a significant percentage of the population5; these factors are related to the morbidity and mortality attributable to COVID 19 infection.6The Centers for Disease Control and Prevention (CDC) describes a list of risk factors for SARS-CoV-2 infection that includes poverty and crowding2. Likewise, a UK-based study investigated the role of ethnicity and socioeconomic position in the development of SARS-CoV-2 infection. They found that socioeconomic deprivation and lack of qualifications were consistently associated with a higher risk of confirmed infection6. Further, reports have shown higher mortality from infectious diseases in patients with a low level of education7. To our knowledge, no studies in Peru have investigated the relationships among the level of education, the socioeconomic status, SARS-CoV-2 infection, and the severity and mortality of the infection, however, statistical findings show a higher frequency of low educational level in people who have died as a result of infection by the virus SARS-CoV-2(Figure 1)Health outcomes are closely related to the educational level. Some types of health behaviors, such as smoking, heavy alcohol drinking, physical inactivity, and unhealthy diet, are expected to mediate the impact of educational level on the incidence of non-communicable diseases8. It is also remarkable that the total prevalence of overweight and obesity in Peru is 60.2% in the total population9. Moreover, lower levels of education are related to higher incidence and prevalence of cardiovascular and cerebrovascular disease, cancer, diabetes, hypertension, and chronic respiratory disease8. Patients with these diseases are at an increased risk of severe illness from COVID-19 because of lower levels of immune cells and high cytokine levels in the body fluids1,2.Educational inequalities in these chronic diseases are mediated by the patient’s socioeconomic status. As expected, low income level and unstable job status that may be linked to low educational level are reasonably predicted to raise the risk of these diseases8. In Peru, > 1/3rd of the population lives in the urban capital, Lima; however, a substantial population still lives in rural areas, with limited access to medical care, chronic disease treatment, and education. These rural residents are often poorer and less educated than their urban counterparts10.Another important factor that influences the characteristics of the COVID-19 pandemic is population density;1 the population density in Peru is 25 people per square kilometer, with a substantial density in the rural population11. Some studies have shown a significant positive linear relationship of population density with number of cases, deaths, and case-fatality rate of SARS-CoV-2. Moreover, there is a significant positive correlation between the number of medical supplies and population density, suggesting that this variable and the lack of medical equipment are key factors that explain the morbidity and mortality of COVID-1912.By 2019, 87% of Peruvians had health insurance coverage;13 however, the quality of health services in the hospitals of the Ministry of Health, in regular situations, is perceived to be low14. The pandemic hit Peru when the country was in the process of improving health services and denoted significant deficiencies across the health system, revealing the need for urgent actions. The lack of equipment, supplies, and medications translates into poor quality of care and plays an important role in the health consequences of the COVID-19 pandemic.In conclusion, we highlight the importance of eliminating the inequality in the coverage of health services and continuing to improve the education for the Peruvian population to control social factors and enable optimal management of the COVID-19 pandemic.

Hydrological models are useful tools for simulating long-term trends in hydrological components resulting from climate and anthropogenic factors. In the present study, long-term hydrological components are simulated using Variable Infiltration Capacity – VIC, a process based model for the time period of 1971-2013 at a resolution of 5.5 km for entire India. The model was calibrated and validated against observed streamflow for all the southern river basins. The simulated soil moisture was also evaluated using in situ observations. It is observed that there is a slight increase in precipitation for Cauvery, Krishna, Ganga and Godavari basins. The model derived soil moisture was converted into percentage available soil moisture (PASM) taking into account of water holding characteristics of soils, which is depicting a good agreement in time and space. Floods and its return period were reconstructed and analyzed by calculating basin wise annual maximum streamflow for the entire period. This modeling framework is developed for the entire country which will contribute towards evaluating and planning for water resources management, its retrospective outlook, mitigating drought, periodic water budgeting, agriculture planning, and irrigation scheduling.

To the Editor,Seroprevalence studies provide a more accurate picture of coronavirus disease 2019 (COVID-19) than PCR-confirmed cases as antibodies can be detected in mild or asymptomatic cases who otherwise remain undiagnosed. Seroprevalence can also be used as an indicator of population immunity. The majority of seroprevalence studies to date have been carried out in developed countries. High levels of herd immunity were recently estimated to be needed to control the spread of COVID-19 in different countries, including Malaysia.1  The first COVID-19 case in Malaysia was reported on January 25, 2020, and the main wave occurred between early March and mid-April. With a national movement control order instituted on March 18, aggressive testing and public health measures, 8,354 cases had been reported as of June 30, 2020,2 or 0.03% of the population. As of June 6, most restrictions had been lifted as part of a phased recovery. We aimed to determine SARS-CoV-2 seroprevalence in residual serum samples collected at a teaching hospital serving Kuala Lumpur and Selangor state, which together have reported 4,483 cases (51.9% of national cases), or 0.05% of the combined population.2 We retrieved 816 serum samples sent for diagnostic testing for non-respiratory infections (mainly dengue) and archived at -20°C. These were divided into periods according to dates of collection: pre-pandemic (June-August 2019, n=228), main wave (January 29 to April 14, 2020, n=327) and post-wave (April 15 to June 6, 2020, n=261). For each period, between 17-65 samples were included from every 10-year age group (<10, 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, and >70 years). The samples were from 368 females and 448 males. Samples were first screened with an in-house indirect ELISA detecting IgG to SARS-CoV-2 receptor binding domain (RBD), and shown to be 100% sensitive for samples collected from 14 days post-onset of illness.3 Screen-seropositive samples were confirmed with a highly sensitive and specific (99.3-100%) surrogate viral neutralization test (sVNT; cPass, GenScript, USA) based on total antibody-mediated blockage of ACE2 receptor-RBD interaction,4,5 which has received provisional authorisation from the Singapore Health Sciences Authority. A two-step testing process of screening with a highly sensitive assay and confirmation with a highly specific assay is useful for low-prevalence settings where seropositives have a low predictive value.5 These two assays were evaluated in our laboratory with the 228 (ELISA) or 26 (sVNT) pre-pandemic serum samples as negative controls and 35 samples collected from PCR-confirmed COVID-19 patients at least 16 days post-onset of illness. Sensitivity and specificity rates for the screening ELISA were 97.1%  and 88.6%, respectively. For the confirmatory sVNT assay, sensitivity and specificity rates were 100%, after increasing the inhibition cut-off from 20% to 25%, as suggested by the manufacturer after assessing background reactivity in our setting. Our two-step testing process thus utilised assays with 97% sensitivity (screening) and 100% specificity (confirmatory), exceeding the United States FDA-recommended minimum sensitivity of 90% and specificity of 95% for serology tests with emergency use authorisation.6 Crude seroprevalence rates are reported with 95% exact binomial confidence intervals (CI) approximated with Poisson distribution.   A total of 46 (7.8%) main wave and post-wave samples screened positive, of which 3 were confirmed by sVNT. Two were from the main wave (seroprevalence 0.6%; 95% CI, 0.07-2.2%) and 1 from the post-wave period (0.4%, 95% CI, 0.01-2.1%) (Figure 1). Two were from males aged in their 20s with previous diagnoses of COVID-19. The third was from a 65-year-old man with a 7-day history consistent with COVID-19, who was not tested for SARS-CoV-2. As rates for the main wave and post-wave periods were similar, they were combined to give a crude seroprevalence rate of 0.5% (95% CI, 0.1-1.5%). Using 2019 age- and gender-stratified population data for Kuala Lumpur and Selangor from the Department of Statistics, Malaysia (http://pqi.stats.gov.my/searchBI.php), a direct age-standardised seroprevalence rate was calculated as 0.4% (95% CI, 0-0.93%). This study is potentially limited by bias arising from use of residual inpatients serum. However, residual serum can provide similar estimates of seroprevalence to cohort studies7 and is a convenient option when preliminary data is needed during a lockdown. The rate may also be underestimated because antibodies may take 2 weeks to appear and may be undetectable in some mild or asymptomatic cases.  The age-standardised seroprevalence of 0.4% for Kuala Lumpur and Selangor found in this study is higher than the period prevalence of confirmed cases of 0.05%. This is consistent with other seroprevalence studies revealing 6-24 times more COVID-19 infections than are reported.8 As this was a single centre study, a more extensive  national serosurvey is necessary to confirm our preliminary indication that Malaysia has experienced limited SARS-CoV-2 transmission to date. With little herd immunity, Malaysia remains highly susceptible to COVID-19 as we emerge from lockdown. Continued vigilance in surveillance and public health measures are critical pending availability of an effective vaccine. Conflicts of interestCWT is a patent holder in cPass. The other authors declare no competing interests. Ethics statement This study was approved by the University Malaya Medical Centre medical ethics committee (no. 2017116-5794). AcknowledgmentsWe are grateful to Professor Lin-Fa Wang, Duke-NUS Medical School, Singapore, and GenScript Biotech for providing the sVNT testing kits.  REFERENCES1. Kwok KO, Lai F, Wei WI, et al. Herd immunity - estimating the level required to halt the COVID-19 epidemics in affected countries. J Infect. 2020;80(6):e32-e33. https://doi.org/10.1016/j.jinf.2020.03.027 2. Ministry of Health Malaysia. 2020. Press statement from the Director-General of Health, 30 June 2020: updates on the coronavirus disease 2019 (COVID-19) situation in Malaysia. https://kpkesihatan.com/2020/06/30/kenyataan-akhbar-kpk-30-jun-2020-situasi-semasa-jangkitan-penyakit-coronavirus-2019-covid-19-di-malaysia/. Accessed on August 8, 2020. 3. Chia WN, Tan CW, Foo R, et al. Serological differentiation between COVID-19 and SARS infections. Emerg Microbes Infect. 2020;9(1):1497-1505. https://doi.org/10.1080/22221751.2020.1780951 4. Tan CW, Chia WN, Chen MIC, et al. A SARS-CoV-2 surrogate virus neutralization test (sVNT) based on antibody-mediated blockage of ACE2-spike (RBD) protein-protein interaction. Nat Biotechnol. 2020. https://doi.org/10.1038/s41587-020-0631-z. 5. Bond K, Nicholson S, Lim S, et al. Evaluation of serological tests for SARS-CoV-2: Implications for serology testing in a low-prevalence setting. J Infect Dis. 2020; https://doi.org/10.1093/infdis/jiaa467.  6. U.S. Food & Drug Administration. In Vitro Diagnostics EUAs - Serology Template for Commercial Manufacturers (updated June 26, 2020). https://www.fda.gov/media/137698/download. Accessed on August 8, 2020. 7. Kelly H, Peck HA, Laurie KL, et al. The age-specific cumulative incidence of infection with pandemic influenza H1N1 2009 was similar in various countries prior to vaccination. PLoS ONE. 2011;6(8):e21828. https://doi.org/10.1371/journal.pone.0021828 8. Havers FP, Reed C, Lim TW, et al. Seroprevalence of antibodies to SARS-CoV-2 in 10 sites in the United States, March 23-May 12, 2020. JAMA Intern Med. 2020. https://doi.org/10.1001/jamainternmed.2020.4130.  Figure legendFIGURE 1. Epidemic curve of COVID-19 in Malaysia in 2020 from the first reported case on January 25 to June 30. The periods of serum sampling are shown (main wave, January 29 to April 14; post-wave, April 15 to June 6) with crude seroprevalence rates (95% CI).

Introduction - Dental anesthetic management in ICD recipients with CCh can be challenging due to the potential risk of life-threatening arrhythmias and appropriate ICD therapies during procedural time. We assessed the hypothesis that the use of local dental anesthesia with 2% lidocaine with 1:100.000 epinephrine or without a vasoconstrictor can be safe in selected ICD and CCh patients, not resulting in life-threatening events. Methods and Results - Restorative dental treatment under local dental anesthesia was made in two sessions, with a wash-out period of 7 days (cross-over trial), conducting with a 28h - Holter monitoring, and 12-lead electrocardiography, digital sphygmomanometry, and anxiety scale assessments in 3 time periods. Ventricular/supraventricular arrhythmias frequency, device shocks, corrected QT interval and dynamic changes in right precordial leads in BrS were also analyzed. All patients were in stable condition with no recent events before the dental care. Twenty-four consecutive procedures were performed in 12 patients (9 women, 3 men) with CCh and ICD: 7 (58.3%) had LQTS, 4 (33.3%) had BrS and 1 (8.3%) had CPVT. Holter analysis did not demonstrated increased heart rate or sustained arrhythmias. Blood pressure, electrocardiographic changes and anxiety measurement showed no statistically significant differences. No life-threatening events occurred during dental treatment, regardless the type of anesthesia. Conclusions - Lidocaine administration, with or without epinephrine, can be safely used in selected CCh-ICD patients without life-threatening events, as long as the protocol is followed. These preliminary findings need to be confirmed in a larger population with ICD and CCh.

Background: The 2019 novel coronavirus disease (COVID-19) has been reported as pandemy and the number of patients continues to rise. Based on recent data, cardiac injury is a prominent feature of the disease, leading to increased morbidity and mortality.In the present study we aimed to evaluate myocardial dysfunction using transthoracic echocardiography (TTE) and tissue Doppler imaging (TDI) in hospitalized COVID-19 patients. Methods and Results: We recruited 30 patients (56.7 % male, 55.80±14.949 years) who were hospitalized with the diagnosis COVID-19 infection. We analyzed left ventricular (LV) and right ventricular (RV) conventional and TDI parameters at the time of hospitalization and during the course of the disease. Patients without any cardiac disease and with preserved LV ejection fraction (EF) were included.TTE examination was performed and all the variables were recorded and analyzed retrospectively. We observed that both LV and RV conventional echocardiographic parameters were similar when the day of admission to the hospital was compared to the 5th day of the disease. Regarding TDI analysis, we demonstrated significant impairment in LV septal and lateral deformation (p˂.001) .In the correlation analysis no marked correlation was observed between impairment in LV deformation and inflammation biomarkers. Conclusion: Cardiac involvement is an important feature of the COVID-19 infection but the exact mechanism is still undefined. Echocardiography is an essential technique to describe myocardial injury and provide new concepts for the possible definitions of cardiac dysfunction.

Background: Ever since the coronavirus disease 2019 (COVID-19) has become a pandemic, worldwide efforts are being made to “flatten the curve”. Israel was amongst the first countries to impose significant restrictions. As a result, cardiac surgeons have been required to scale down their routine practice, resulting in a significant reduction in the number of cardiac surgeries. The aim of this study is to characterize the impact of COVID-19 on cardiac surgery in Israel. Methods: This is a retrospective observational study performed in two cardiac surgery departments in Israel and includes all patients who underwent cardiac surgery in March and April during the years 2019 and 2020. The patient cohort was divided into two groups based on the year of operation. Analysis of the patients’ baseline characteristics, operative data, and postoperative outcome, was performed. Results: The 2019 group (n=173), and the 2020 group (n=108) were similar regarding their baseline characteristics, previous medical history, and rates of previous revascularization interventions. However, compared to the 2019 group, patients in the 2020 group were found to be more symptomatic (NYHA class IV; 2.4% vs. 6.2%, p=0.007). While all patients underwent similar procedures, patients in the 2020 group had significantly longer procedural time (p<0.001). In-hospital mortality rate was found to be significantly higher in group 2020 (13% vs. 5.2%, p=0.037). Conclusions: While the number of patients undergoing cardiac surgery declined during the outbreak period, the rate of surgical mortality increased. One explanation for this might be delayed hospital arrival.

Persistent left superior vena cava can create technical challenges during implantation of pacing devices; which, in the majority of cases, are implanted on the left side. We present a chest x-ray of a patient with a left-sided biventricular implantable cardioverter defibrillator placement through a persistent left SVC.

Venous thromboembolism (VTE) is a life-threatening complication rarely encountered with the use of combined oral contraceptives (COCs). Obesity is an additional thrombosis risk factor that has been shown to further increase the risk of VTE with the use of COCs. We present five cases of obese adolescents (BMI >30 kg/m2) who encountered thrombosis complications while on COCs. Although the absolute risk of VTE events in the setting of COCs is rare, caution should be observed when choosing hormonal therapy and safer COCs alternatives discussed with adolescents who are obese.

The Gulf of Mannar (GoM), located between India and Sri Lanka, has astonishing faunal richness and diversity1. Two oceanographic data sets are discussed here to show the unique ecological setting in the GoM sustaining a rich and diverse fauna. We tested the hypothesis that a specific stretch of a large marine environment behaves differently from the rest of the region due to its peculiar geographical positioning. Primarily, unlike the adjacent Indian southwestern shelf, coastal upwelling and the associated seasonal oxygen deficiency, potentially imparting physiological stress to marine fauna2-7, does not occur in the GoM. Secondly, the GoM along the Indian coastline receives adequate amount of primary (plankton) food from the Arabian Sea and the Bay of Bengal through the seasonally reversing coastal currents8-12. Thirdly, the GoM water has high transparency, aerated and sandy seafloor conducive for the growth of diverse corals and many sensitive fauna1,4. Our studies show that oxygen deficiency sheltered geography has a significant role in facilitating significantly high faunal diversity and richness in the GoM. We suggest that other similar coastal environments worldwide, protected from the extended oxygen-deficient region, might be functioning as a refuge for marine life and thereby increased faunal diversity6,7.

Spatial patterns of biodiversity are inextricably linked to their collection methods, yet no synthesis of these patterns or their consequences exists. As such, our view of ecosystems may be incorrect, undermining countless ecological and evolutionary studies. Using 742 million records of 374,900 species, we explore the global patterns and impacts of accessibility in terrestrial and marine Systems. Pervasive sampling and observation biases exist across animals, with only 6.74% of the globe sampled, and disproportionately poor tropical sampling. High-elevations and deep-seas are comparably unknown. Over 50% of records in most groups account for under 2% of species. Citizen-science exacerbates biases, and normalizing the practice of valuing data publication is essential to bridge this gap and better represent species distributions from more distant and inaccessible areas, and provide the necessary basis for conservation and management.

A giant granuloma obstructing the upper airway in a 21-year-old male is described. It arose after an extreme psychological stress. The patient underwent microlaryngoscopic removal of the granuloma, with no recurrence. This case confirms the role of psychological stress in the pathogenesis of laryngeal granulomas, that can reach huge dimensions.

Background: Bioinformatics software often lacks graphical user interfaces (GUIs), which can limit its adoption by non-technical members of the scientific community. Web interfaces are a common alternative for building cross-platform GUIs, but their potential is underutilized: web interfaces for command-line tools rarely take advantage of the level of interactivity expected of modern web applications and are rarely usable offline.Results: Here we present Pline: a lightweight framework that uses program descriptions and web standards to generate dynamic GUIs for command-line programs. We introduce a plugin system for creating Pline interfaces and provide an online repository for sharing third-party plugins. We demonstrate Pline’s versatility with example interfaces, a graphical pipeline for sequence analysis and integration to Wasabi web application.Conclusions: Pline is cross-platform, open-source software that can be integrated to web pages or used as a standalone desktop application. Pline provides graphical interfaces that are easy to create and maintain, fostering user-friendly software in science. Documentation, demo website, example plugins and source code is freely available from http://wasabiapp.org/pline. Keywords: Bioinformatics; Software Engineering; User Interfaces; Web Technologies

Dear Editor,We read the article on possible effects of BCG vacaccine in COVID-19 management should be discouraged and restricted to research purpose only.2

Several recent studies have reported that systemic corticosteroids were effective against coronavirus disease 2019 (COVID-19) (1). Patients with severe COVID-19 present with acute respiratory distress syndrome (ARDS), also known as diffuse alveolar damage, presumably caused by an excessive immune response in the alveoli. Similar but milder alveolar inflammation may also exist in early stage patients, and systemic corticosteroids may contribute to the suppression of excessive inflammation in the alveoli, however, adverse effects such as opportunistic infections and delayed viral elimination may outweigh this advantage. This could be why the study by Horby et al. found no benefit in less severe patients who were not receiving oxygen (1). Delivering corticosteroids directly to the alveoli by inhalation should be effective and would have fewer systemic side effects. SARS-CoV-2 infection is suggested to elicit inflammatory cytokine secretion, not only from alveolar macrophages but also from alveolar epithelial type 2 cells (2). Additionally, ICS (inhaled corticosteroids) deposited in the alveoli enter the systemic circulation via the pulmonary vasculature, leading to potential anti-inflammatory effects in this region, which is also considered to be a site of inflammation during COVID-19.Nebulized budesonide improved oxygenation and significantly reduced inflammatory markers (TNF-α, IL-1β, and IL-6) in patients with ARDS (3). There are several reviews of inhaled corticosteroids for COVID-19, and currently, there is no clear evidence on whether pre-morbid use of ICS is a factor in adverse or beneficial outcomes for COVID-19 (4,5).ICS can reach different sites in the lungs, depending on particle size (5). As the alveoli are considered to be the main site for lung inflammation in COVID-19, steroids with smaller particle sizes that can reach the alveoli should be more promising. Among ICS, pressurized metered-dose inhalers (pMDIs) of beclomethasone and ciclesonide have the smallest particle sizes (<2 µm) and, thus, are considered to reach the alveoli more easily (6). The particles in the nebulizer are also small enough to reach the alveoli, but there is a concern that the particles that return on exhalation may contain the virus and could therefore infect medical personnel.Apart from their anti-inflammatory effects, some ICS have been found to have antiviral effects. Ciclesonide and mometasone, which are both marketed as ICS, suppressed the replication of SARS-CoV-2 and MERS-CoV in vitro, whereas dexamethasone, cortisone, prednisolone, and fluticasone did not (7). There is a case report of three COVID-19 patients treated with inhaled ciclesonide (8). Although it might be more difficult for dry powder inhalers (DPI) to reach the alveoli, owing to their larger particle size, than for pMDIs (6), mometasone may be worth considering, as it has antiviral properties and a smaller particle size than budesonide (6). A mutant MERS-CoV that developed resistance to ciclesonide did not show resistance to mometasone (7).ICS should be considered as a promising therapeutic candidate, and should be prioritized for clinical trials in both mildly symptomatic outpatients and severely ill inpatients. As of July 5, 2020, several clinical trials worldwide utilizing ICS for COVID-19 have been registered on ClinicalTrials.gov: four trials (one recruiting, three not yet) for ciclesonide, and four trials (three recruiting, one not yet) for budesonide (one including formoterol).The antiviral effect of ICS as well as their particle size, which is related to the ability to reach the alveoli, should also be noted. The anti-SARS-COV-2 effect of beclomethasone in vitro has yet to be tested. We propose that clinical trials that confirm the clinical effect of beclomethasone, which has a similar particle size to ciclesonide, as well as studies that confirm its antiviral effect, should be conducted. This is because, if either or both drugs are found to be effective it may be possible to speculate whether these effects are due to the antiviral or anti-inflammatory effects. If beclomethasone is found to be clinically effective but not antiviral, the effect of particle size can be estimated by comparing it to budesonide, which also has no antiviral effect. For the same reason and in anticipation of the unique antiviral effect that is different from ciclesonide, we propose that clinical trials of mometasone, which has a smaller but similar particle size to budesonide, should also be conducted. Mometasone is also available in nasal spray form. Clinical trials could be conducted to determine the preventive effects of intranasal mometasone and its effectiveness in treating early stage COVID-19. References 1.         Horby P, Lim WS, Emberson J, et al. Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report. medRxiv 2020 Jun. doi: https://doi.org/10.1101/2020.06.22.201372732.         Huang J, Hume AJ, Abo KM, et al. SARS-CoV-2 Infection of pluripotent stem cell-derived human lung alveolar type 2 cells elicits a rapid epithelial-intrinsic inflammatory response. bioRxiv 2020 Jun. doi: https://doi.org/10.1101/2020.06.30.1756953.         Mohamed HS, Meguid MM. Effect of nebulized budesonide on respiratory mechanics and oxygenation in acute lung injury/acute respiratory distress syndrome: Randomized controlled study. Saudi J Anaesth. 2017 Jan-Mar;11(1):9-14. doi:10.4103/1658-354X.1973694.         Maes T, Bracke K, Brusselle GG. COVID-19, Asthma, and Inhaled Corticosteroids: Another Beneficial Effect of Inhaled Corticosteroids?. Am J Respir Crit Care Med. 2020 Jul;202(1):8-10. doi:10.1164/rccm.202005-1651ED5.        Halpin DMG, Singh D, Hadfield RM. Inhaled corticosteroids and COVID-19: a systematic review and clinical perspective. Eur Respir J. 2020 May;55(5):2001009. doi:10.1183/13993003.01009-20206.         Nave R, Mueller H. From inhaler to lung: clinical implications of the formulations of ciclesonide and other inhaled corticosteroids. Int J Gen Med. 2013;6:99-107. doi:10.2147/IJGM.S391347.         Matsuyama S, Kawase M, Nao N, et al. The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15. bioRxiv 2020 Mar. doi: https://doi.org/10.1101/2020.03.11.9870168.         Iwabuchi K, Yoshie K, Kurakami Y, et al. Therapeutic potential of ciclesonide inhalation for COVID-19 pneumonia: Report of three cases. J Infect Chemother. 2020 Jun;26(6):625-632. doi:10.1016/j.jiac.2020.04.007  

This systematic review evaluates the efficacy, safety and economic impact of dupilumabcompared to standard of care for uncontrolled moderate-to-severe atopic dermatitis (AD). Pubmed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important AD-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Seven RCTs including 1845 subjects > 12 years treated with dupilumab16 to 52 weeks were evaluated. For adultsthere is high certainty that dupilumabdecreasesSCORAD (MD -30,72; 95%CI -34,65% to -26,79%) and EASI-75 (RR 3.09; 95%CI 2.45 to 3.89), pruritus (RR 2.96; 95%CI 2.37 to 3.70), rescue medication (RR 3.46; 95%CI 2.79 to 4.30), sleep disturbance (MD -7.29; 95%CI -8.23 to -6.35), anxiety/depression (MD -3.08; 95% CI -4.41 to -1.75) and improves quality of life (MD -4.80; 95% CI -5.55 to -4.06). The efficacy for adolescents is similar. Dupilumab-related adverse events (AEs) slightly increase (low certainty). The evidence for dupilumab-related serious AE is uncertain. The incremental cost-effectiveness ratio ranged from 28,500 £ (low certainty) to 124,541 US$ (moderate certainty).More data on long term safety are needed both for children and adults, together with more efficacy data in the paediatric population.

Resumo: Este é um Grupo de Revisores de pré-impressão da Revista Ensino & Pesquisa. O texto avaliado foi  Uma escola atraente é um convite para estudar: Erasmo Pilotto e a educação  paranaense na década de 1950, de Márcia Marlene Stentzler e Cláudia Sena Lioti. O artigo das autoras Marcia Stentzler e Claudia Sena Lioti aborda aspectos da história da Educação do Paraná , configurando a história a partir de Erasmo Pilotto intelectual da educação com expressão no Paraná no início do século XX. O artigo bem estruturado tem excelentes referencias que são base na área de história da educação , como Bourdieu (1998, 2007); Le Goff (2003); Miceli (2007).A pesquisa trabalha com as categorias de analise sobre o intelectual, considerando o capital sociocultural, para destacar a influência da escola nova. O trabalho, resgata a trajetória de Erasmo Pilotto, colocando em foco sua experiência de vida e formação acadêmica em prol da educação no Paraná. A pesquisa destaca a importância da área de história da educação no Brasil e no Paraná, evidencia o quanto é necessário os percursos históricos e biográficos dos intelectuais que estiveram a frente de processos educativos escolarizados, para análise critica sobre a constituição do processo de escolarização no Brasil, e em específico no Paraná! Conforme indicam as autoras em sua pesquisa Erasmo Pilotto fez parte do grupo de intelectuais que trabalhou em prol de uma escola pública unificada, laica e ativa no Estado do Paraná. À luz dos princípios da Escola Nova e experiências exitosas em outros Estados, como por exemplo Rio de Janeiro, São Paulo e Bahia, num momento histórico em que o discurso governamental era pela modernização e democratização, a educação era a ponte para alcançar esses resultados, conforme demonstram pesquisas de Miguel (1994), Vieira e Marach (2007), Silva (2009, 2014) e Monteiro (2015), entre outras.O artigo tem o objetivo de compreender aspectos do pensamento de Pilotto e sua ação pedagógica a partir do capital sociocultural acumulado. Ainda as autoras investigam as origens e vivências que perpassaram a prática do educador, cujo trabalho se entretece ao percurso histórico e educacional do Estado, até meados do século XX. O artigo tem três tópicos, o primeiro discute a conjuntura paranaense da época: As primeiras décadas do Século XX no Paraná e a influência do intelectual, Conforme indica Stentzler (2015) o final da primeira década do século XX marcou o sul do Paraná e norte de Santa Catarina pela conclusão da ferrovia que ligava São Paulo ao Rio Grande do Sul. Os estados do Paraná e Santa Catarina viviam um clima conflituoso, de disputa territorial e, no ano de 1910, o Estado do Paraná perdia, novamente, recurso e embargo judicial para Santa Catarina quanto a posse do território do Contestado. O clima de conflito se acirrava, culminando na Guerra do Contestado, entre 1912 e pelo menos 1916, envolvendo sertanejos, forças governamentais e milicianos, entre outros. Na região sul do Paraná, numa localidade hoje pertencente ao município de Rebouças, nascia Erasmo Pilotto, no ano 1910, (SILVA, 2009). Naquela região, o trem já trafegava há pelo menos 5 anos. A ferrovia simbolizava o progresso e a modernização para as cidades e populações do interior do Estado do Paraná. O segundo tópico elabora a a figura de Pilotto: Erasmo Pilotto: uma trajetória pela educação, Erasmo: um educador de alma romântica, obra escrita por Anita Camargo Pilotto (1987), a autora descreve suas atitudes profissionais por meio de anotações extraídas de seu diário. No entendimento da autora, Erasmo era possuidor de uma alma romântica. (PILOTTO, 1987). A amorosidade de sua esposa também revelava seu capital sociocultural e os seus bens simbólicos, nesta perspectiva, atribuímos à Erasmo Pilotto preocupação com uma verdadeira transformação social por meio da educação. O terceiro tópico apresenta o movimento escola nova na vida e obra desse intelectual. Erasmo Pilotto lutou pela inserção das ideias da Escola Nova no Paraná, assim como em outros estados e em âmbito nacional, Fernando Azevedo (1894–1974), Lourenço Filho (1897-1970), Anísio Teixeira (1900–1971) e outros representam a busca por transformações curriculares na educação, tendo por base os ideais do escolanovismo. Segundo Vieira e Marach (2007, p. 270), estes educadores são “um exemplo sem precedentes na história brasileira do  poder de mobilização da causa educacional na formação de um grupo de intelectuais sofisticados e, sobretudo, influentes na sociedade brasileira”. Consideradas as especificidades da pesquisa, as representações acerca da educação e concepções teóricas podem ser compreendidas a partir de condições sociais favoráveis “à separação e divisão do trabalho simbólico”, uma vez que a “atividade teórica, repousa, portanto, no privilégio” de ser lugar para compreender determinações, fatos simbólicos que correspondam à realidade, (MICELI, 2007, p. XXXVII). O trabalho é significativo para a área de história da Educação e conforme considerações finais da autora a perspectiva bourdieusiana, Erasmo Pilotto superou a expectativa do seu grupo social e alcançou a fração intelectualizada da elite paranaense. Ele foi um agente intelectual e político que, com sensibilidade e espírito científico, logrou importantes renovações e fez parte de uma profunda mudança nos paradigmas da educação do nosso Estado.ReferencesBLOCH, Marc. Apologia da História ou o ofício do historiador. Rio de Janeiro: Jorge Zahar Editora, 2001. BOURDIEU, Pierre. Escritos de Educação. Petrópolis: Vozes, 1998. BOURDIEU, Pierre. A economia das trocas simbólicas. Introdução, organização e seleção Sergio Miceli. São Paulo: Perspectiva, 2007. (Coleção estudos). DEWEY, John. Experiência e educação. 3.ed. São Paulo: Ed. Nacional, 1979. GADOTTI, Moacir. História das Ideias Pedagógicas. São Paulo: Ática, 1996. HUSS, Silvana Rodrigues Malheiro. O processo de escolarização no município de Mandaguari-Pr (1949-1988). Dissertação (Mestrado em Educação). Programa de Pós-graduação em Educação da Universidade Estadual de Maringá. 2012.LAZIER, Hermógenes. Paraná: Terra de todas as gentes e de muita história. Francisco Beltrão: Grafit-gráfica e Editora Ltda, 2003. LE GOFF, Jacques. História e Memória. 5. ed. Campinas, SP: UNICAMP, 2003. MEC. INEP. CILEME. A educação do Paraná: síntese sobre o ensino público elementar e médio. No.3. Rio de Janeiro, 1954. (Série de monografias sobre os sistemas estaduais de educação). MICELI, Sergio. Introdução. In: BOURDIEU, Pierre. A economia das trocas simbólicas. Introdução, organização e seleção Sergio Miceli. São Paulo: Perspectiva, 2007. (Coleção estudos).MIGUEL, Maria Elisabeth, Blanco. A formação do professor e a organização social do trabalho. Curitiba: UFPR, 1997. MIGUEL, Maria Elisabeth, Blanco. O significado do trabalho de Erasmo Pilotto no cenário educacional paranaense. In: Educar em Revista. n.10. Curitiba: UFPR, 1994.MONTEIRO, Cicília Rodrigues. Contribuições de Erasmo Pilotto para expansão do ensino primário no Paraná: ensino rural, alfabetização e formação de professores (1940-1970). 91 f. Dissertação (Mestrado em Educação). Programa de Pós-graduação em Educação da Universidade Estadual de Maringá. 2015. MONTEIRO, Cicília Rodrigues; SCHELBAUER, Analete Regina. Erasmo Pilotto a idealização da escola perfeita: a criação do Instituto Pestalozzi. In: Seminário do PPE. Universidade Estadual de Maringá. Maringá: UEM, 2015. OLIVEIRA, Maria Cecília Marins. Organização Escolar no início do século XX: o caso do Paraná. In: Educar em Revista. No. I 8. Curitiba: UFPR, 2001. pp. 143-155. PILOTTO, Anita. Erasmo: um educador de alma romântica. Curitiba: Editora Rocha, 1987. PILOTTO, Erasmo. Prática de Escola Serena. Curitiba: [s.l.],1946. PILOTTO, Erasmo. A educação é direito de todos. Curitiba: [s.l.], 195PROSSER, Elizabeth Seraphim. Cem anos de sociedade, arte e educação em Curitiba (1853-1953): da Escola de Belas Artes e Indústrias, de Mariano de Lima, à Universidade do Paraná e à Escola de Música e Belas Artes do Paraná. Curitiba: Ed. Assembleia Legislativa do Paraná, 2004. PUGLIELLI, Helio de Freitas. Erasmo Pilotto. Curitiba: Editora da UFPR, 1996. (Série Paranaenses, n. 7). RELATÓRIO da Instrução Pública do Paraná, 1928. Disponível em https://www.arquivopublico.pr.gov.br/arquivos/File/RelatoriosSecretarios/Ano_1928_MFN_1038.pdf . Acesso em: 21 de maio de 2020.ROMANOVSKI, Natália. Os moços da província: a Revista Joaquim e o campo literário no Paraná. Monografia. Curso de Ciências Sociais, Setor de Filosofia, Ciências Humanas e Letras, Universidade Federal do Paraná. Curitiba, 2008. SANTOS, Denise Grein (org). Autobiografia: Erasmo Pilotto. Curitiba, PR: UFPR, 2004. SILVA, Rossano. A arte como princípio educativo: um estudo sobre o pensamento educacional de Erasmo Pilotto. Dissertação (Mestrado em Educação) – Universidade Federal do Paraná, Curitiba, 2009. SILVA, Rossano. Educação, Arte e Política: a trajetória intelectual de Erasmo Pilotto. 2014. Tese (Doutorado em Educação) – Universidade Federal do Paraná, Curitiba, 2014. STENTZLER, Márcia Marlene. Entre questões lindeiras e a superação de fronteiras: a escola complementar em Porto União (SC) e União da Vitória (PR)1928-1928. 2015. Tese (Doutorado em Educação). Programa de Pós-Graduação em Educação da Universidade Federal do Paraná, Curitiba, 2015.VIEIRA, Carlos Eduardo; MARACH, Caroline Baron. Escola de Mestre único e a escola serena: realidade e idealidade no pensamento de Erasmo Pilotto. In: VIEIRA, Carlos Eduardo (org.). Intelectuais, educação e modernidade no Paraná. Curitiba: UFPR, 2007. XAVIER, Luiz Antonio. Relatório Apresentado a Exmo. Sr. Francisco Xavier da Silva, Presidente do Estado do Paraná. Curityba: Typ. Da República, 1910. Disponível em: http://www.arquivopublico.pr.gov.br/arquivos/File/RelatoriosSecretarios/Ano_1910_MFN_743.pdf Acesso em: 17de maio de 2020.XAVIER, Luiz Antonio. Relatório Apresentado a Exmo. Sr. Francisco Xavier da Silva, Presidente do Estado do Paraná. Curityba: Typ. Da República, 1911. Disponível em: https://www.scielo.br/scielo.php?script=sci_nlinks&ref=000111&pid=S0104-4060200100020000800045&lng=en Acesso em: 24 de maio de 2020.