Oculomotor, vestibular, reaction time, and cognitive tests as objective measures of neural deficits in patients post COVID-19 infection.

Objective: An alarming proportion (>30%) of patients affected by SARS-CoV-2 (COVID-19) continue to experience neurological symptoms, including headache, dizziness, smell and/or taste abnormalities, and impaired consciousness (brain fog), after recovery from the acute infection. These symptoms are self-reported and vary from patient to patient, making it difficult to accurately diagnose and initiate a proper treatment course. Objective measures to identify and quantify neural deficits underlying the symptom profiles are lacking. This study tested the hypothesis that oculomotor, vestibular, reaction time, and cognitive (OVRT-C) testing using eye-tracking can objectively identify and measure functional neural deficits post COVID-19 infection. Methods: Subjects diagnosed with COVID-19 (n = 77) were tested post-infection with a battery of 20 OVRT-C tests delivered on a portable eye-tracking device (Neurolign Dx100). Data from 14 tests were compared to previously collected normative data from subjects with similar demographics. Post-COVID subjects were also administered the Neurobehavioral Symptom Inventory (NSI) for symptom evaluation. Results: A significant percentage of post COVID-19 patients (up to 86%) scored outside the norms in 12 out of 14 tests, with smooth pursuit and optokinetic responses being most severely affected. A multivariate model constructed using stepwise logistic regression identified 6 metrics as significant indicators of post-COVID patients. The area under the receiver operating characteristic curve (AUC) was 0.89, the estimated specificity was 98% (with cutoff value of 0.5) and the sensitivity was 88%. There were moderate but significant correlations between NSI domain key variables and OVRT-C tests. Conclusions: This study demonstrates the feasibility of OVRT-C testing to provide objective measures of neural deficits in people recovering from COVID-19 infection. Such testing may serve as an efficient tool for identifying hidden neurological deficits post COVID-19, screening patients at risk of developing long COVID, and may help guide rehabilitation and treatment strategies.

Origin and population structure of Brazilian hair sheep breeds.

Brazilian hair sheep constitute a genetic diversity hotspot. These animals are found in the harsh environments of the Brazilian Northwest (semi-arid) region. Genotypes (50K SNP chip) from seven Brazilian sheep breeds (five hair and two coarse wool types) and 87 worldwide breeds were used to test for population structure, admixture and genetic diversity. Moreover, phylogenetic trees evaluating migration events between genetic groups were built. Brazilian Somali, a fat-tailed breed, had a close relationship with East African breeds and clustered distinctly from other Brazilian breeds. Brazilian Blackbelly and Barbados Blackbelly had a close relationship. The Morada Nova breed did not show close relationships with European or African breeds, revealing a single migration event from an Algerian hair breed. Brazilian Fat-tail and Morada Nova share a common ancestor, but the former showed introgressions from Brazilian Somali and Afrikaner breeds, explaining the fat-tail phenotype. The Santa Inês breed received a substantial contribution from Brazilian Bergamasca and showed an admixed origin with recent introgressions from other breeds, mainly from Suffolk. Furthermore, Brazilian Somali and Brazilian Fat-tail are the most endangered sheep genetic resources in Brazil and should be the focus for ex situ conservation programs. In conclusion, Brazilian hair sheep show an African origin and are characterized by diverse genetic composition, reinforcing the need for conservation of these genetic resources, and at the same time, this highly diverse group has variability that can be used in breeding programs.

COPD: Analysing factors associated with a successful treatment.

OBJECTIVES: To evaluate if non-adherence to inhaled medications, inhalers mishandling or the prescribers' non-adherence to GOLD strategy are associated with mMRC grade, CAT score, COPD acute exacerbations or FEV1%. METHODS: A cross-sectional study on COPD was conducted in the ambulatory pulmonary clinic of Hospital de Guimarães. Patients ≥40 years diagnosed according to GOLD criteria were recruited consecutively. A survey of demographic and clinical data was used. Adherence was assessed by using the Measure of Treatment Adherence (MTA) questionnaire. Inhalation technique was evaluated by using checklists of correct steps and critical errors, and inhalers' misuse was defined when one or more critical errors were made, whatever the number or types of inhalers in use. To evaluate the prescriber non-adherence to GOLD strategy, the patients' current medication was compared with therapeutic standards proposed by the GOLD 2017 strategy for the same ABCD groups. A statistical analysis was performed with IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp. RESULTS: We studied 303 participants, 79.5% males, mean age=67.5 years. A total of 285 completed the MTA questionnaire. Non-adherence was referred by 47 (16.5%) patients, and a significant negative association was found between adherence and CAT score and FEV1%. 285 patients performed 499 inhalations manoeuvres with 10 different IDs. Inhaler misuse was observed in 113 (39.6%) patients, and was not associated with CAT score, mMRC grade, ECOPD or FEV1%. We found deviations from the GOLD strategy in 133 (44.3%) patients, which were negatively related to CAT score, mMRC grade and ECOPD. CONCLUSIONS: In the present study we failed to prove a positive association between non-adherence to medication, inhalers mishandling or prescribers' non-adherence to GOLD strategy with symptoms, exacerbations and airflow limitation. Conversely, more symptomatic and more obstructed patients were more adherent to medication, previous ECOPD seems to improve prescribers' adherence to treatment guidelines, and symptoms, ECOPD and FEV1% were not significantly associated with inhaler technique.

COPD: misuse of inhaler devices in clinical practice.

Background and objectives: Inhalers mishandling remain an important clinical issue worldwide. The aim of this study was to evaluate inhalation technique in stable COPD out-patients. The variables under study were type of inhaler device (ID), patients' preference for an inhaler, number of IDs used by each patient, beliefs about inhaler medication and some demographic, clinical and functional patients' characteristics. We aim to assess how they are related to inhalation technique. Methods: A cross-sectional study was conducted in a hospital outpatient respiratory care. COPD patients over 40 years old, diagnosed according to GOLD criteria, and using IDs were included consecutively. The Beliefs about Medicines Questionnaire (BMQ), a demographic and a clinical survey were applied. The number of IDs used by each patient and the patients' preference for some IDs were recorded. Patients were asked to demonstrate the use of their prescribed inhalation devices, and inhaler technique was assessed by using previously defined checklists, including essential steps and critical errors. A statistics analysis was then performed. Results: We studied 300 subjects performing a total of 521 inhalation manoeuvers with 10 different IDs. At least one step incorrectly performed was found in 48.2% of demonstrations and in 29.9% critical errors were observed. Misuse was related to priming/loading in 6.9%, to inhalation manoeuver in 13.1% and to both in 10%. There was a statistically significant association between critical errors and type of ID (P<0.001). No significant relationship was found between correct performance of key manoeuvers and patients' preference or number of inhalers used per patient. Misuse due to critical errors was observed in 39.3% of patients and was positively related to female gender, age ≥65, lower education level and lower socioeconomic status (higher Graffar classification score), but not to patients' clinical or functional characteristics. In the sub-group of patients presenting critical errors when using IDs, there was a statistically significant inverse association between BMQ Necessity score and number of critical errors. Conclusions: Inhalers mishandling remains disappointingly common. A good inhalation technique depends on the type of ID, and failure of inhalation manoeuver was the main cause of ID misuse. It was not associated to multiple inhalers' use nor to patient's preference, but to the patient's beliefs about the necessity to use them. Elderly patients, women and those with lower education level or lower socioeconomic status demonstrate a worse inhalation technique.

Characterisation of morbidity in a COPD hospital cohort.

OBJECTIVES: To characterise the morbidity of COPD out-patients based on symptoms, acute exacerbations, FEV1 and comorbidities, and to explore the association between different patients' characteristics such as social, demographic, clinical history or exposure. METHODS: Stable COPD outpatients over 40 years old diagnosed according to GOLD criteria were included consecutively; the exclusion criteria were only refusal to participate and inability to understand clinical questionnaires. A survey of demographic and clinical data was conducted. Symptoms were evaluated using the CAT and mMRC questionnaires. The number of COPD acute exacerbations reported in the previous year was assessed, and spirometry performed on all participants according to ATS/ERS recommendations. Different variables were collected and then related to each other. RESULTS: We studied 303 COPD outpatients, all Caucasians, 79.5% males and mostly elderly. 65.7% of participants reported having low monthly income and 87.8% a low education level. Tobacco smoking was the most common exposure identified but a substantial proportion of COPD patients were non-smokers (26%). Frequent acute exacerbations were reported by 38.0% of patients. The mean post-bronchodilator FEV1 was 53.2%. The distribution of patients according to GOLD 2017 stage and classification was respectively 9.9%, 41.9%, 35.0% and 13.2% from 1 to 4 and 23.1%, 39.6%, 2.3% and 35.0% from GOLD A to D. Only 29 patients (9.5%) presented no comorbid conditions, and the most common were hypertension, heart diseases and dyslipidaemia. CONCLUSIONS: Our data confirms COPD as a complex and heterogeneous disorder, with a significant morbidity due to the nature of symptoms, frequent comorbidities and exacerbations. A substantial proportion of COPD patients were never-smokers, mainly women, calling attention to the need for COPD recognition in these cases. COPD in women, in never-smokers and in patients with a previous diagnosis of asthma presented some specific characteristics. Some patient characteristics are associated with frequent acute exacerbations. FEV1 was strongly related both to symptoms and exacerbations.

[Prevalence of abdominal aortic aneurysm in patients with chronic obstructive pulmonary disease]. / Prevalência de aneurisma da aorta abdominal em indivíduos com doença pulmonar obstrutiva crónica.

INTRODUCTION: The association of the abdominal aortic aneurysm (AAA) to the chronic obstructive pulmonary disease (COPD) is questionable. Both entities share the same risk factors and physiopathology, which is based on a persistent pro- -inflammatory response, proteolysis and excessive extracellular matrix turnover. OBJECTIVES: To determine the AAA prevalence in a sample of patients with COPD. METHODS: Identification of patients with COPD and abdominal CT, hospitalized in a level 2 hospital between January 2015 and December 2016. RESULTS: In a sample with 100 patients, 5 presented an AAA. There were no significant differences between patients with and without AAA regarding gender (100% versus 69,5% male), age (74,80±6,22 versus 71,23±12,36 years), comorbidities (myocardial infarction 0% versus 1,1%; stroke 0% versus 10,5%), cardiovascular risk factors (diabetes mellitus 20% versus 23,2%; hypertension 80% versus 50,5%) and spirometric results. Patients with AAA were significantly more medicated with acetylsalicylic acid and had more aortic thrombi (P=0,031 and P=0,002, respectively). No correlation was found between the aortic size and the forced expiratory flow in one second values. DISCUSSION: The AAA prevalence of our sample was 5%, twice the described for the Portuguese population (2,37%). This is the first study conducted in Portugal to determine the AAA prevalence in COPD patients. CONCLUSION: The study of the relationship between both diseases could contribute to a more effective screening of AAA, by determining a group with increased risk, which could lead to a reduction of the mortality rates associated with the ruptured aneurysm.

Introdução: A associação entre aneurisma da aorta abdominal (AAA) e doença pulmonar obstrutiva crónica (DPOC) é discutível. Ambas as doenças partilham os mesmos fatores de risco e fisiopatologia, baseados numa resposta pro-inflamatória persistente, proteólise e turnover excessivo da matriz extracelular. Objetivos: Determinar a prevalência de AAA numa população com DPOC. Métodos: Identificaram-se os doentes com DPOC e que realizaram TC abdominal, internados num hospital de nível 2, entre janeiro de 2015 e dezembro de 2016. Resultados: Numa amostra de 100 doentes, 5 apresentavam AAA. Comparando o grupo com e sem AAA, verificou-se inexistência de diferenças significativas relativamente ao género (100% versus 69,5% sexo masculino), idade (74,80±6,22 versus 71,23±12,36 anos), comorbilidades (DAC 0% versus 1,1%; AVC 0% versus 10,5%), fatores de risco cardiovascular (diabetes mellitus 20 % versus 23,2%; hipertensão arterial 80% versus 50,5%) e resultados de espirometria. Verificaram-se diferenças significativas relativamente à medicação com ácido acetilsalicílico e presença de trombo aórtico (P=0,031 e P=0,002, respetivamente). Não se encontrou correlação entre os valores dos diâmetros aórticos e do FEV1. Discussão: Nesta amostra, a prevalência de AAA foi de 5%, duas vezes superior à da população portuguesa (2,37%). Este é o primeiro estudo realizado em Portugal para determinar a prevalência de AAA em DPOCs. Conclusão: O estudo da relação entre as duas patologias poderá contribuir para um rastreio mais eficaz do AAA, ao identificar um grupo de risco aumentado, o que poderá levar a uma diminuição da mortalidade associada ao aneurisma em rotura.

Operational Characterization of Pressure Regulating Valves.

The functionality of pressure regulating valves (PRVs) is important for proper uniformity and efficiency of irrigation during center pivot irrigation, especially when the center pivot operates on sloping terrain. In practice, the regulated pressure at the PRV outlet is slightly influenced by its inlet pressure, the flow rate through it, and hysteresis effects. The objectives of this work were (a) to evaluate operational characteristics of PRVs based on requirements stated by ISO 10522 (1993) and (b) to model the regulated pressure as a function of inlet pressure and flow rate through the valve considering hysteresis. We carried out tests to evaluate regulation uniformity, regulation curve, hysteresis, and the regulated pressure as function of flow rate and inlet pressure. The following three models of PRVs were evaluated: 10 PSI, 15 PSI, and 20 PSI. For each model, three samples were tested under increasing and decreasing conditions of inlet pressure, within the range from 49.03 to 784.53 kPa, with increments of 49.03 kPa. In addition, flow rates were tested within the range of 0 and 4 m3 h-1. From the gathered data, models to predict outlet pressure as a function of inlet pressure and flow rate were fitted.

Comprehensive analysis by liquid chromatography Q-Orbitrap mass spectrometry: Fast screening of peptides and organic molecules.

The number of substances nominally listed in the prohibited list of the World Anti-Doping Agency increases each year. Moreover, many of these substances do not have a single analytical target and must be monitored through different metabolites, artifacts, degradation products, or biomarkers. A new analytical method was developed and validated for the simultaneous analysis of peptides and organic molecules using a single sample preparation and LC-Q-HRMS detection. The simultaneous analysis of 450 target molecules was performed after cleanup on a mixed-mode solid-phase extraction cartridge, combined with untreated urine. The cleanup solvent and reconstitution solvent were the most important parameters for achieving a comprehensive sample preparation approach. A fast chromatographic run based on a multistep gradient was optimized under different flows; the detection of all substances without isomeric coelution was achieved in 11 minutes, and the chromatographic resolution was considered a critical parameter, even in high-resolution mass spectrometry detection. The mass spectrometer was set to operate by switching between positive and negative ionization mode for FULL-MS, all-ion fragmentation, and FULL-MS/MS2 . The suitable parameters for the curved linear trap (c-trap) conditions were determined and found to be the most important factors for the development of the method. Only FULL-MS/MS2 enables the detection of steroids and peptides at concentrations lower than the minimum required performance levels set by World Anti-Doping Agency (1 ng mL-1 ). The combination of the maximum injection time of the ions into the c-trap, multiplexing experiments, and loop count under optimized conditions enabled the method to be applied to over 10 000 samples in only 2 months during the 2016 Rio Summer Olympic and Paralympic Games. The procedure details all aspects, from sample preparation to mass spectrometry detection. FULL-MS data acquisition is performed in positive and negative ion mode simultaneously and can be applied to untargeted approaches.

One Hundred Consecutive Liver Transplants Using Institutes Georges Lopez-1 Preservation Solution: Outcomes and Prognostic Factors.

BACKGROUND: There are only 4 prior studies reporting on outcomes of liver transplantation (LT) using Institutes Georges Lopez-1 (IGL-1) preservation solution. Detection of negative predictors of LT using IGL-1 may help finding strategies to protect selected recipients at higher risk of graft failure and death. METHODS: Review of all consecutive adult patients who underwent a first whole-graft LT using IGL-1 at authors' institution from 2013 to 2016. Primary end point was graft failure within the first 90 postoperative days (PODs). Graft losses due to any cause (including all deaths with a functioning graft) were recorded as graft failures. RESULTS: Of all 100 patients included in this study, 37 were women; median age was 58 years (range 18-71). There were 12 graft losses during the first 90 PODs (including 3 cases of primary nonfunction of the liver allograft), and 10 of the 12 graft losses occurred on first 30 PODs. All 12 patients who experienced graft loss (including 1 patient who underwent liver retransplantation) died within the first 90 PODs. Of the total 100 patients, 14 experienced biliary complications. Univariate analysis revealed prolonged warm ischemic time (WIT) as the only predictor of 90-day graft failure (odds ratio = 23.5, confidence interval = 1.29-430.18, P = .03). The cutoff by receiver operating characteristic curve for WIT was 38 minutes (area under the curve = 0.70). Positive predictive value for WIT >38 minutes was 94.3%. CONCLUSIONS: LT using IGL-1 can be performed safely. Similar to prior reports on LT using other preservation solutions, prolonged WIT was associated with adverse outcomes.

Unexpected seasonality in quantity and composition of Amazon rainforest air reactivity.

The hydroxyl radical (OH) removes most atmospheric pollutants from air. The loss frequency of OH radicals due to the combined effect of all gas-phase OH reactive species is a measureable quantity termed total OH reactivity. Here we present total OH reactivity observations in pristine Amazon rainforest air, as a function of season, time-of-day and height (0-80 m). Total OH reactivity is low during wet (10 s(-1)) and high during dry season (62 s(-1)). Comparison to individually measured trace gases reveals strong variation in unaccounted for OH reactivity, from 5 to 15% missing in wet-season afternoons to mostly unknown (average 79%) during dry season. During dry-season afternoons isoprene, considered the dominant reagent with OH in rainforests, only accounts for ∼20% of the total OH reactivity. Vertical profiles of OH reactivity are shaped by biogenic emissions, photochemistry and turbulent mixing. The rainforest floor was identified as a significant but poorly characterized source of OH reactivity.

Sustained magnetization oscillations in polyaniline-Fe3O4 nanocomposites.

We report experiments with polyaniline-Fe3O4 (PANI-Fe3O4) nanocomposites synthesized under several different conditions. With a reaction carried out at room temperature and assisted by intense ultra-violet (UV) irradiation, we observe sustained oscillations in the magnetization with a period of about 25 min. The oscillations are interpreted as the result of an oscillatory chemical reaction in which part of the Fe(+2) ions of magnetite, Fe3O4, are oxidized by the UV irradiation to form Fe(+3) so that a fraction of the magnetite content transforms into maghemite, γ-Fe2O3. Then, Fe(+3) ions at the nanoparticle surfaces are reduced and transformed back into Fe(+2), when acting as an oxidizing agent for polyaniline in the polymerization process. Since maghemite has smaller magnetization than magnetite, the oscillating chemical reaction results in the oscillatory magnetization. The observations are interpreted with the Lotka-Volterra nonlinear coupled equations with parameters that can be adjusted to fit very well the experimental data.

Total tract nutrient digestion and milk fatty acid profile of dairy cows fed diets containing different levels of whole raw soya beans.

Whole oilseeds such as soya beans have been utilized in dairy rations to supply additional fat and protein. However, antinutritional components contained in soya beans, such as trypsin inhibitors and haemagglutinins (lectins) may alter digestibility of nutrients and consequently affect animal performance. The objective of the present experiment was to quantify the effect of different levels of whole raw soya beans in diets of dairy cows on nutrient intake, total tract digestion, nutrient balances and milk yield and composition. Sixteen mid to late-lactation cows (228 ± 20 days in milk; mean ± SD) were used in four replicated 4 × 4 Latin square design experiment with 21-d periods. Cows were assigned to each square according to milk yield and DIM. The animals were randomly allocated to treatments: control (without soya beans addition; CO), WS9, WS18 and WS27, with addition of 9%, 18% and 27% of whole raw soya bean in diet on a dry matter (DM) basis respectively. All diets contained identical forage and concentrate components and consisted of maize silage and concentrate based on ground corn and soya beans at a ratio of 60:40. There were no differences in OM, CP, NDF and NEL intakes (kg/day and MJ/day) among the treatments (p > 0.05). However, DM and NFC intakes were negatively affected (p = 0.04 and p < 0.01, respectively) and ether extract (EE) intake was positively affected (p < 0.01). Total tract digestion increased linearly with whole raw soya beans for EE (p < 0.01) and NDF (p = 0.01). The excretion (kg/day) of digested soya beans grains increased linearly according to addition of whole raw soya beans. However, the nutritive characteristics of excreted grains were not altered. Milk (kg), milk lactose (kg) and protein (kg) yield decreased linearly (p < 0.01, p < 0.01 and p = 0.04, respectively) milk fat content (%) increased linearly (p < 0.01) with whole raw soya beans inclusion. Increasing addition of whole raw soya beans affected milk fatty acid profile with a linear decrease of cis-9-trans 11CLA and total saturated FA; and linear increase of total unsaturated and C18:3 FA. Energy balance was positively affected (p = 0.03) by whole raw soya beans as well as efficiency of NEL milk/DE intake (p = 0.02). Nitrogen balance and microbial protein synthesis were not affected by whole raw soya beans. Increasing doses of whole raw soya beans decreased dry matter intake and milk yield, however, led to an increase of unsaturated acids in milk and higher milk fat concentration.

Nuclear and mitochondrial genome instability induced by senna (Cassia angustifolia Vahl.) aqueous extract in Saccharomyces cerevisiae strains.

Cassia angustifolia Vahl. (senna) is commonly used in self-medication and is frequently used to treat intestine constipation. A previous study involving bacteria and plasmid DNA suggested the possible toxicity of the aqueous extract of senna (SAE). The aim of this study was to extend the knowledge concerning SAE genotoxicity mechanisms because of its widespread use and its risks to human health. We investigated the impact of SAE on nuclear DNA and on the stability of mitochondrial DNA in Saccharomyces cerevisiae (wt, ogg1, msh6, and ogg1msh6) strains, monitoring the formation of petite mutants. Our results demonstrated that SAE specifically increased Can(R) mutagenesis only in the msh6 mutant, supporting the view that SAE can induce misincorporation errors in DNA. We observed a significant increase in the frequency of petite colonies in all studied strains. Our data indicate that SAE has genotoxic activity towards both mitochondrial and nuclear DNA.

Cytotoxic, mutagenic and genotoxic evaluation of crude extracts and fractions from Piper jericoense with trypanocidal action.

The current Chagas disease treatment is based on two drugs, nifurtimox and benznidazole, which is considered unsatisfactory, not only because of the narrow therapeutic range but also because of the associated toxicity. Natural products are considered an important source of biologically active compounds against various infectious organisms. Numerous Piper species are used in traditional medicine to treat parasitic diseases. In this paper, we study the activity of extracts and fractions obtained from Piper jericoense plant against epimastigote, trypomastigote and amastigote forms of Trypanosoma cruzi. In addition, we evaluated the cytotoxic, mutagenic and genotoxic activities of the F4 fraction obtained from one of the more promising extracts. We obtained four extracts, one of which presented low toxicity and high trypanocidal activity. This extract was separated into eight fractions, and the F4 fraction presented better results than the other extracts and had a higher selectivity index than the reference drug, benznidazole. This fraction was not cytotoxic, mutagenic or genotoxic.

Ultrastructure and morphogenesis of the wing scales in Heliconius erato phyllis (Lepidoptera: Nymphalidae): what silvery/brownish surfaces can tell us about the development of color patterning?

Usually the literature on Heliconius show three types of scales, classified based on the correlation between color and ultrastructure: type I - white and yellow, type II - black, and type III - orange and red. The ultrastructure of the scales located at the silvery/brownish surfaces of males/females is for the first time described in this paper. Besides, we describe the ontogeny of pigmentation, the scale morphogenesis and the maturation timing of scales fated to different colors in Heliconius erato phyllis. The silvery/brownish surfaces showed ultrastructurally similar scales to the type I, II and III. The ontogeny of pigmentation follows the sequence red, black, silvery/brownish and yellow. The maturation of yellow-fated scales, however, occurred simultaneously with the red-fated scales, before the pigmentation becomes visible. In spite of the scales at the silvery/brownish surfaces being ultrastructurally similar to the yellow, red and black scales, they mature after them; this suggests that the maturation timing does not show a relationship with the scale ultrastructure, with the deposition timing of the yellow pigment. The analysis of H. erato phyllis scale morphogenesis, as well as the scales ultrastructure and maturation timing, provided new findings into the developmental architecture of color pattern in Heliconius.