Visual manifestations in giant cell arteritis: identification of risk factors from the ARTESER Registry.

OBJECTIVE: To determine the prevalence and predictive factors of visual manifestations in a large registry of patients with GCA. METHODS: ARTESER is a large Spanish multicentre registry supported by the Spanish Society of Rheumatology. It includes patients with GCA from across the entire country diagnosed between June 2013 and March 2019. The variables collected at diagnosis were demographics, clinical manifestations (including all visual manifestations), laboratory, temporal artery biopsy, and imaging findings (ultrasound, FDG-PET/CT, MRI angiography, CT angiography). Patients with and without visual involvement were compared in a bivariate analysis. Multivariate logistic regression was performed to determine potential predictive factors of visual manifestations. RESULTS: The study population comprised 1636 GCA patients, of whom 599 (36.6%) presented visual manifestations. Anterior ischemic optic neuropathy was the most frequent (n = 274 of 599; 45.7%) ocular complication. The independent predictors that increased the risk (OR; 95% confidence interval) of visual involvement were older age (1.027; 1.009-1.045) and jaw claudication (1.724; 1.325-2.243). The variables associated with a reduced risk were polymyalgia rheumatica (0.541; 0.414-0.708), fever (0.373; 0.264-0.527), longer symptom duration (0.946; 0.909-0.985), and higher erythrocyte sedimentation rate (ESR) (0.992; 0.988-0.997), common features of patients with large vessel-GCA. CONCLUSION: One-third of GCA patients present visual manifestations at diagnosis. Older age and jaw claudication are independent predictors of visual manifestations, whereas polymyalgia rheumatica, fever, longer symptom duration, and high ESR reduce the risk of visual involvement.

Lifting COVID-19 mitigation measures in Spain (May-June 2020).

Introduction: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. Methods: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. Results: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. Conclusion: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

Introducción: El 14 de marzo de 2020 España declaró el estado de alarma por la pandemia por COVID-19 incluyendo medidas de confinamiento. El objetivo es describir el proceso de desescalada de estas medidas. Métodos: Un plan de transición hacia una nueva normalidad, del 28 de abril, incluía 4 fases secuenciales incrementando progresivamente las actividades socioeconómicas y la movilidad. Concomitantemente, se implementó una nueva estrategia de diagnóstico precoz, vigilancia y control. Se estableció un mecanismo de decisión bilateral entre Gobierno central y comunidades autónomas (CCAA), guiado por un panel de indicadores cualitativos y cuantitativos de la situación epidemiológica y las capacidades básicas. Las unidades territoriales evaluadas comprendían desde zonas básicas de salud hasta CCAA. Resultados: El proceso se extendió del 4 de mayo al 21 de junio y se asoció a planes de refuerzo de las capacidades en las CCAA. La incidencia disminuyó de una mediana inicial de 7,4 por 100.000 en 7 días a 2,5 al final del proceso. La mediana de pruebas PCR aumentó del 53% al 89% de los casos sospechosos, y la capacidad total de 4,5 a 9,8 pruebas semanales por 1.000 habitantes; la positividad disminuyó del 3,5% al 1,8%. La mediana de casos con contactos trazados aumentó del 82% al 100%. Conclusión: La recogida y análisis sistemático de información y el diálogo interterritorial logaron un adecuado control del proceso. La situación epidemiológica mejoró, pero sobre todo, se aumentaron las capacidades, en todo el país y con criterios comunes, cuyo mantenimiento y refuerzo fue clave en olas sucesivas.

m6A RNA Degradation Products Are Catabolized by an Evolutionarily Conserved N6-Methyl-AMP Deaminase in Plant and Mammalian Cells.

N6-methylated adenine (m6A) is the most frequent posttranscriptional modification in eukaryotic mRNA. Turnover of RNA generates N6-methylated AMP (N6-mAMP), which has an unclear metabolic fate. We show that Arabidopsis thaliana and human cells require an N6-mAMP deaminase (ADAL, renamed MAPDA) to catabolize N6-mAMP to inosine monophosphate in vivo by hydrolytically removing the aminomethyl group. A phylogenetic, structural, and biochemical analysis revealed that many fungi partially or fully lack MAPDA, which coincides with a minor role of N6A-RNA methylation in these organisms. MAPDA likely protects RNA from m6A misincorporation. This is required because eukaryotic RNA polymerase can use N6-mATP as a substrate. Upon abrogation of MAPDA, root growth is slightly reduced, and the N6-methyladenosine, N6-mAMP, and N6-mATP concentrations are increased in Arabidopsis. Although this will potentially lead to m6A misincorporation into RNA, we show that the frequency is too low to be reliably detected in vivo. Since N6-mAMP was severalfold more abundant than N6-mATP in MAPDA mutants, we speculate that additional molecular filters suppress the generation of N6-mATP. Enzyme kinetic data indicate that adenylate kinases represent such filters being highly selective for AMP versus N6-mAMP phosphorylation. We conclude that a multilayer molecular protection system is in place preventing N6-mAMP accumulation and salvage.

e-Health as a tool to improve the quality of life of informal caregivers dealing with stroke patients: Systematic review with meta-analysis.

OBJECTIVE: The objective of this review was to elucidate the evidence related to utilizing e-Health as a tool in improving the quality of life of informal caregivers of dependent patients due to cerebrovascular accident (CVA). METHODS: This systematic review with meta-analysis includes 13 studies. For these studies, seven databases were searched between 2009 and 2019. A random-effects model was adopted for overall estimation and to explain the heterogeneity. RESULTS: A random-effects model was adopted for overall estimation and to explain heterogeneity. The results did not demonstrate statistical significance (p<0.05) and low heterogeneity (I2  = 0). CONCLUSIONS: There is a tendency toward improvement in psychological health, solving care-related problems, as well as better prevention of problems arising from the burden. Therefore, new studies with larger sample size and primarily to conduct them for more than 6 months for the accuracy. CLINICAL RELEVANCE: This study reflects a trend toward improving psychological health, solving care-related problems, as well as improved the prevention of problems arising from the burden.

Correction to: Rain-Fed Granite Rock Basins Accumulate a High Diversity of Dormant Microbial Eukaryotes.

The original version of this article contained an erratum of omission in the Acknowledgments section.

Rain-Fed Granite Rock Basins Accumulate a High Diversity of Dormant Microbial Eukaryotes.

Rain fed granite rock basins are ancient geological landforms of worldwide distribution and structural simplicity. They support habitats that can switch quickly from terrestrial to aquatic along the year. Diversity of animals and plants, and the connexion between communities in different basins have been widely explored in these habitats, but hardly any research has been carried out on microorganisms. The aim of this study is to provide the first insights on the diversity of eukaryotic microbial communities from these environments. Due to the ephemeral nature of these aquatic environments, we predict that the granitic basins should host a high proportion of dormant microeukaryotes. Based on an environmental DNA diversity survey, we reveal diverse communities with representatives of all major eukaryotic taxonomic supergroups, mainly composed of a diverse pool of low abundance OTUs. Basin communities were very distinctive, with alpha and beta diversity patterns non-related to basin size or spatial distance respectively. Dissimilarity between basins was mainly characterised by turnover of OTUs. The strong microbial eukaryotic heterogeneity observed among the basins may be explained by a complex combination of deterministic factors (diverging environment in the basins), spatial constraints, and randomness including founder effects. Most interestingly, communities contain organisms that cannot coexist at the same time because of incompatible metabolic requirements, thus suggesting the existence of a pool of dormant organisms whose activity varies along with the changing environment. These organisms accumulate in the pools, which turns granitic rock into high biodiversity microbial islands whose conservation and study deserve further attention.

Environmentally-driven gene content convergence and the Bacillus phylogeny.

BACKGROUND: Members of the Bacillus genus have been isolated from a variety of environments. However, the relationship between potential metabolism and the niche from which bacteria of this genus have been isolated has not been extensively studied. The existence of a monophyletic aquatic Bacillus group, composed of members isolated from both marine and fresh water has been proposed. Here, we present a phylogenetic/phylogenomic analysis to investigate the potential relationship between the environment from which group members have been isolated and their evolutionary origin. We also carried out hierarchical clustering based on functional content to test for potential environmental effects on the genetic content of these bacteria. RESULTS: The phylogenetic reconstruction showed that Bacillus strains classified as aquatic have evolutionary origins in different lineages. Although we observed the presence of a clade consisting exclusively of aquatic Bacillus, it is not comprised of the same strains previously reported. In contrast to phylogeny, clustering based on the functional categories of the encoded proteomes resulted in groups more compatible with the environments from which the organisms were isolated. This evidence suggests a detectable environmental influence on bacterial genetic content, despite their different evolutionary origins. CONCLUSION: Our results suggest that aquatic Bacillus species have polyphyletic origins, but exhibit convergence at the gene content level.

miR-181 elevates Akt signaling by co-targeting PHLPP2 and INPP4B phosphatases in luminal breast cancer.

The PI3K-Akt pathway is one of the most commonly dysregulated cancer-associated signaling pathways. Here we report an oncogenic function for the miR-181 family in luminal breast cancer cells that involves Akt hyperactivation. We show that miR-181a and miR-181d posttranscriptionally suppress the expression of PHLPP2 and INPP4B phosphatases, resulting in elevated growth factor-induced Akt phosphorylation. Ectopic expression of miR-181a and miR-181d promoted S-phase entry and cell proliferation, which was reversed by pharmacological Akt inhibition. Importantly, the expression of miR-181 family members and PHLPP2/INPP2B are inversely correlated in primary human estrogen receptor-positive breast cancers, supporting the clinical relevance of our findings.

The use of intracardiac echocardiography during percutaneous pulmonary valve replacement.

High-quality live imaging assessment of cardiac valves and cardiac anatomy is crucial for the success of catheter-based procedures. We present our experience using Intracardiac echocardiography (ICE) during transcatheter Percutaneous Pulmonary Valve replacement (tPVR).This is a retrospective study that included 35 patients who underwent tPVR between April 2008 and June 2012. Thirty-one of these patients had the procedure performed under continuous ICE guidance. Pre-procedure transthoracic echocardiography (TTE) was obtained in all patients. ICE was performed at baseline, during the procedure, and at the conclusion of the procedure. Comparisons between the pre-procedure TTE and baseline ICE data and between post-procedure ICE data and the following day TTE were performed. Total of 35 patients had tPVR during the above-mentioned time period. Twenty-one patients received the Edwards Sapien valve and 14 patients had the Melody valve. Thirty-one patients had the procedure performed under continuous ICE guidance. The mean Pre-TTE peak gradient (PG) and Pre-ICE-PG were 45.5 ± 20 vs 33 ± 13 mmHg (p < 0.001) and the mean Pre-TTE mean gradient (MG) and Pre-ICE-MG were 27.7 ± 13 vs 21 ± 18 mmHg (p < 0.001). The mean Post-TTE- PG and Post-ICE-PG were 24.3 ± 11 vs 15.3 ± 7 mmHg (p < 0.001) and the mean of the Post-TTE-MG and Post-ICE-MG were 14.2 ± 7 vs 8.4 ± 4 mmHg (p < 0.001). There was a good correlation between peak ICE and TTE gradient at baseline and after valve placement. For the degree of pulmonary regurgitation, there was no significant difference between TTE and ICE. ICE is an important modality to guide tPVR in patients with dysfunctional homograft valve between the right ventricle and pulmonary artery and should be used to assess valve function before, during and immediately after the procedure.

Single-center outcome analysis comparing reintervention rates of surgical arterioplasty with stenting for branch pulmonary artery stenosis in a pediatric population.

Although catheter-based intervention is generally accepted as the treatment of choice for branch pulmonary artery (PA) stenosis, there are no data directly comparing both the need for reintervention and time to reintervention in patients undergoing transcatheter stenting versus surgical arterioplasty. We compared children who underwent surgical branch pulmonary arterioplasty and branch PA stent placement between January 2008 and May 2012 at a single tertiary center. Need for reintervention and mean time to reintervention were assessed using chi-square and independent sample Student t test. Thirty-seven patients were included (surgery n = 18, stent n = 19). Mean weight at initial intervention was 11.3 ± 8.8 kg for surgical and 20.1 ± 15.5 kg for stent (p = 0.041). Intervention was performed on the left PA in 17 patients, the right PA in 12 patients, and both PAs in 8 patients. Five patients had undergone previous intervention. On mean follow-up of 807 ± 415 days, 50% (9 of 18) of the surgery cohort and 5.3% (1 of 19) of the stent cohort required reintervention (p = 0.002). In all but one case reintervention was catheter-based. Mean time to reintervention for the surgery cohort was 272 ± 162 days and for the single stent cohort it was 150 days. When comparable age and weight groups were analyzed, reintervention was still more common in the surgery cohort (p = 0.007). Children undergoing surgical branch pulmonary arterioplasty are more likely to require reintervention than those undergoing stent placement.

Isolation and characterization of gallium resistant Pseudomonas aeruginosa mutants.

Pseudomonas aeruginosa PA14 cells resistant to the novel antimicrobial gallium nitrate (Ga) were developed using transposon mutagenesis and by selecting spontaneous mutants. The mutants showing the highest growth in the presence of Ga were selected for further characterization. These mutants showed 4- to 12-fold higher Ga minimal inhibitory growth concentrations and a greater than 8-fold increase in the minimum biofilm eliminating Ga concentration. Both types of mutants produced Ga resistant biofilms whereas the formation of wild-type biofilms was strongly inhibited by Ga. The gene interrupted in the transposon mutant was hitA, which encodes a periplasmic iron binding protein that delivers Fe³âº to the HitB iron permease; complementation of the mutant with the hitA gene restored the Ga sensitivity. This hitA mutant showed a 14-fold decrease in Ga internalization versus the wild-type strain, indicating that the HitAB system is also involved in the Ga uptake. Ga uptake in the spontaneous mutant was also lower, although no mutations were found in the hitAB genes. Instead, this mutant harbored 64 non-silent mutations in several genes including those of the phenazine pyocyanin biosynthesis. The spontaneous mutant produced 2-fold higher pyocyanin basal levels than the wild-type; the addition of this phenazine to wild-type cultures protected them from the Ga bacteriostatic effect. The present data indicate that mutations affecting Ga transport and probably pyocyanin biosynthesis enable cells to develop resistance to Ga.

Medium and long-term outcomes after bilateral pulmonary artery stenting in children and adults with congenital heart disease.

Percutaneous stenting of branch pulmonary arteries (PAs) has become an important interventional therapy in the complete management of congenital heart disease. Few data exist on long-term outcomes for patients requiring placement of bilateral stents. This study aimed to determine the medium- to long-term outcomes after bilateral stenting of branch PAs in patients with congenital heart disease. A retrospective study analyzed all procedural and follow-up data on patients undergoing bilateral PA stenting during a single procedure. From October 2001 to May 2012, 26 patients underwent bilateral PA stenting (total of 62 stents). The mean age of these patients was 9.5 ± 12 years, and their mean weight was 27 ± 19 kg. The mean procedural time was 191 ± 67 min, and the mean fluoroscopy time was 50 ± 29 min. The mean gradient across the right pulmonary artery decreased from 35 ± 22 to 11 ± 12 mmHg (p < 0.001). The left pulmonary artery gradient decreased from 32 ± 17 to 10 ± 12 mmHg (p < 0.001), and the right ventricle to descending aorta pressure ratio decreased from 71 ± 18 % to 46 ± 13 % (p < 0.001). Intraprocedural adverse events were encountered in four patients (1 small PA dissection, 2 intraprocedural arrhythmias, and 1 first-degree burn on the thigh). The mean follow-up period was 41 ± 23 months. Two deaths occurred. Further interventions were required for 12 patients. Bilateral PA stenting is effective and safe, with an instantaneous significant decrease in pressure gradients. The need for reintervention is common, so continued follow-up assessment is warranted.

The pediatric cardiology pharmacopeia: 2013 update.

The use of medications plays a pivotal role in the management of children with heart diseases. Most children with increased pulmonary blood flow require chronic use of anticongestive heart failure medications until more definitive interventional or surgical procedures are performed. The use of such medications, particularly inotropic agents and diuretics, is even more amplified during the postoperative period. Currently, children are undergoing surgical intervention at an ever younger age with excellent results aided by advanced anesthetic and postoperative care. The most significant of these advanced measures includes invasive and noninvasive monitoring as well as a wide array of pharmacologic agents. This review update provides a medication guide for medical practitioners involved in care of children with heart diseases.

New electronic implementation of the timestamps method intended for high resolution comparison of laser wavelengths.

This article describes a new measurement system for the comparison of two electronic signals of different frequencies with application to high resolution comparison of laser wavelengths using a Michelson interferometer. It was built within the framework of research projects made by the University of Vigo and the Laboratorio Oficial de Metroloxía de Galicia (LOMG) in cooperation with Escolas Proval High School. The new hardware is based on a cheap high-speed module for the acquisition of data and a microcontroller module for processing, which can also be used for practical lessons in vocational training. The system has been tested with electronic signal generators. The novel measurement method reduces the uncertainty using multiple consecutive measurements and the fractional part of the fringes and could achieve precisions in the range 10-12 of the wavelength ratios.

Pandrug-resistant Acinetobacter baumannii from different clones and regions in Mexico have a similar plasmid carrying the blaOXA-72 gene.

Background: Multidrug-resistant Acinetobacter baumannii is a common hospital-acquired pathogen. The increase in antibiotic resistance is commonly due to the acquisition of mobile genetic elements carrying antibiotic resistance genes. To comprehend this, we analyzed the resistome and virulome of Mexican A. baumannii multidrug-resistant isolates. Methods: Six clinical strains of A. baumannii from three Mexican hospitals were sequenced using the Illumina platform, the genomes were assembled with SPAdes and annotated with Prokka. Plasmid SPAdes and MobRecon were used to identify the potential plasmid sequences. Sequence Type (ST) assignation under the MLST Oxford scheme was performed using the PubMLST database. Homologous gene search for known virulent factors was performed using the virulence factor database VFDB and an in silico prediction of the resistome was conducted via the ResFinder databases. Results: The six strains studied belong to different STs and clonal complexes (CC): two strains were ST208 and one was ST369; these two STs belong to the same lineage CC92, which is part of the international clone (IC) 2. Another two strains were ST758 and one was ST1054, both STs belonging to the same lineage CC636, which is within IC5. The resistome analysis of the six strains identified between 7 to 14 antibiotic resistance genes to different families of drugs, including beta-lactams, aminoglycosides, fluoroquinolones and carbapenems. We detected between 1 to 4 plasmids per strain with sizes from 1,800 bp to 111,044 bp. Two strains from hospitals in Mexico City and Guadalajara had a plasmid each of 10,012 bp pAba78r and pAba79f, respectively, which contained the bla OXA-72 gene. The structure of this plasmid showed the same 13 genes in both strains, but 4 of them were inverted in one of the strains. Finally, the six strains contain 49 identical virulence genes related to immune response evasion, quorum-sensing, and secretion systems, among others. Conclusion: Resistance to carbapenems due to pAba78r and pAba79f plasmids in Aba pandrug-resistant strains from different geographic areas of Mexico and different clones was detected. Our results provide further evidence that plasmids are highly relevant for the horizontal transfer of antibiotic resistance genes between different clones of A. baumannii.

Lifting COVID-19 mitigation measures in Spain (May-June 2020).

INTRODUCTION: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. METHODS: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. RESULTS: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. CONCLUSION: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

Giant pulmonary valve cyst in a 7-year-old child.

This report describes the diagnosis and surgical management of a pulmonary valve cystic mass in a symptomatic 7-year-old boy. Cardiac valve cysts are extremely rare beyond the age of 6 months and typically not associated with symptoms. These lesions may grow, leading to progressive stenosis, regurgitation, or ventricular outflow tract obstruction. Therefore, these lesions should be monitored for change in size and/or, hemodynamic changes. Surgical intervention may be required for symptomatic patients.

Validation of Content for an App for Caregivers of Stroke Patients through the Delphi Method.

The aim of this study was to reach a consensus among experts (using the Delphi technique) to validate the informative content that should be included in an App to be used by informal caregivers of stroke patients in order to improve their quality of life, facilitating access to the health care system and involving them in their own health. This technique was developed between June and December 2021. The group of experts was selected on the basis of previously established criteria, and the coefficient of variation (v) was used as a measure of consensus. In addition, the concordance index was calculated to determine the stability of the different rounds. In the first round, the preliminary content, previously elaborated by the research group, was evaluated as very appropriate for the objectives set (N-P < 1.07). In addition, averages of 4.5 out of five and a coefficient of variation of less than 0.5 were obtained, confirming the consensus. In the second round, suggestions were made by the experts on how to improve the content of the information, obtaining 100% agreement with the results obtained in the first round. The results obtained allow a positive evaluation of the use of the Delphi method for the elaboration of the information to be housed in an App.

Racial/Ethnic Disparities in Parent Activation: Implications for Developing Interventions Addressing Early Childhood Obesity.

OBJECTIVE: Examine racial/ethnic differences in parent activation and associations with child obesity risk behaviors in low-income families. METHODS: Cross-sectional survey study of 300 low-income Black, Latinx, and White parents of patients aged 2 to 5 years receiving primary care within 2 health care systems (Systems 1 & 2). In-person and phone surveys were conducted. Parent activation, defined as parents' knowledge, confidence, and willingness to act concerning their child's health, was measured using the standardized 13-item Parent Patient Activation Measure (P-PAM). Differences in parent activation by race/ethnicity were assessed using analysis of variance. Multivariate regression analyses were used to test associations between parent activation and child obesity risk behaviors. RESULTS: In pooled unadjusted analyses, Latinx parents had significantly lower activation compared to Black parents (P = .023), but these differences were no longer statistically significant after adjusting for other sociodemographic characteristics (P = .06). Higher activation was associated with slightly greater odds of consuming ≥ 5 daily servings of fruits and vegetables for System 2 only (odds ratio: 1.04, 95% confidence interval: 1.01, 1.07). Associations between parental activation and child screen time or physical activity were not significant. CONCLUSIONS: Findings highlight potential measurement limitations of the P-PAM including the inability of the measure to capture barriers to health system navigation and cultural and linguistic considerations. Further attention to the nuanced interplay between parental activation and contextual and sociodemographic risk factors (eg, food availability, immigrant status, economic opportunity, language proficiency) should be considered in the development of early childhood obesity interventions in primary care settings.