Spectrum of variants associated with inherited retinal dystrophies in Northeast Mexico.

BACKGROUND: Inherited retinal dystrophies are hereditary diseases which have in common the progressive degeneration of photoreceptors. They are a group of diseases with clinical, genetic, and allelic heterogeneity. There is limited information regarding the genetic landscape of inherited retinal diseases in Mexico, therefore, the present study was conducted in the northeast region of the country. METHODS: Patients with inherited retinal dystrophies were included. A complete history, full ophthalmological and medical genetics evaluations, and genetic analysis through a targeted NGS panel for inherited retinal dystrophies comprising at least 293 genes were undertaken. RESULTS: A total of 126 patients were included. Cases were solved in 74.6% of the study's population. Retinitis pigmentosa accounted for the most found inherited retinal disease. Ninety-nine causal variants were found, being USH2A and ABCA4 the most affected genes (26 and 15 cases, respectively). CONCLUSIONS: The present study documents the most prevalent causative genes in IRDs, as USH2A, in northeastern Mexico. This contrasts with previous reports of IRDs in other zones of the country. Further studies, targeting previously unstudied populations in Mexico are important to document the genetic background of inherited retinal dystrophies in the country.

Evolución de la bronquiolitis en los servicios de urgencias extrahospitalarias de la Comunidad de Madrid: estudio observacional 2016-2023 / Bronchiolitis trends in out-of-hospital urgent care services in the Community of Madrid: Observational study, 2016-2023

Introducción: La bronquiolitis se convierte en todo un reto durante su pico estacional, desbordando los recursos materiales y humanos para poder atender los pacientes afectados. A consecuencia de ello, se multiplican exponencialmente los traslados interhospitalarios. No se han encontrado estudios que hayan analizado las características de los pacientes con bronquiolitis aguda (BA) en los servicios de urgencias extrahospitalarios (SUEH) y la influencia de la pandemia en su epidemiología. Objetivo: Conocer las características de los pacientes pediátricos y neonatales con bronquiolitis en los SUEH de la Comunidad de Madrid y analizar la influencia de la pandemia por COVID-19 en su epidemiología. Material y métodos: Estudio observacional descriptivo, transversal y retrospectivo realizado en los SUEH de la Comunidad de Madrid entre 2016 y 2023. Se incluyeron pacientes con diagnóstico de BA según CIE-10 en las historias clínicas de las asistencias y traslados interhospitalarios. Se registraron variables sociodemográficas, clínicas y de tratamiento (ventilatorio y farmacológico). Resultados: Se incluyeron 630 pacientes con BA: 343 atendidos por los SUEH no especializados en neonatología (no-neo) y 287 por el equipo de transporte neonatal (TN). La mediana de edad fue de 3,7meses [2,8-4,7] en SUEH no-neo y de 19días [14,2-23,7] en TN. Hubo un aumento de la edad estadísticamente significativo en la temporada 2020/2021 en el grupo de SUEH no-neo. La escala de gravedad fue estadísticamente mayor en el grupo de TN. Hubo un pico inusual de casos de bronquiolitis en junio de 2021, coincidiendo con el fin de la 4.ª ola de COVID-19. La incidencia de bronquiolitis, tras la 6.ª ola de pandemia, fue la mayor de todas las temporadas (13,5 casos por cada 10.000 niños ≤2años)...(AU)

Introduction: Bronchiolitis poses a considerable challenge during its seasonal peak, overwhelming the material and human resources available to care for affected patients. As a result, interhospital transfers increase exponentially. We did not find any studies analysing the characteristics of patients with bronchiolitis managed in out-of-hospital urgent care (OHUC) services and the impact of the COVID-19 pandemic on the epidemiology of bronchiolitis. Objective: To establish the characteristics of paediatric and neonatal patients with acute bronchiolitis (AB) managed in OHUC services in the Community of Madrid and to analyse the impact of the COVID-19 pandemic on the epidemiology of bronchiolitis. Methods: Retrospective cross-sectional observational and descriptive study carried out in OHUC settings in the Community of Madrid between 2016 and 2023. We included patients with a diagnosis of acute bronchiolitis based on the ICD-10 codes documented in the electronic records of urgent care visits and interhospital transports. We collected data on sociodemographic, clinical and treatment (ventilation and medication) variables. Results: The sample included 630 patients with AB: 343 managed in non-neonatal OHUC (non-neo) services and 287 by the mobile neonatal intensive care unit transport team (NTT). The median age was 3.7months (IQR: 2.8-4.7) in patients in the non-neo OHUC group and 19days (IQR: 14.2-23.7) in the NTT group. There was a statistically significant increase in age in the 2020/2021 season in the non-neo OHUC group. The severity score was significantly higher in the NTT group. There was an unusual peak in bronchiolitis cases in June 2021, coinciding with the end of the fourth wave of the COVID-19 pandemic. The incidence of bronchiolitis was highest after the sixth wave of the pandemic (13.5 cases per 10,000 children aged <2years)...(AU)

Conjunctival ultraviolet autofluorescence as a biomarker of outdoor exposure in myopia: a systematic review and meta-analysis.

Outdoor exposure is considered the primary modifiable risk factor in preventing the development of myopia. This effect is thought to be attributed to the light-induced synthesis and release of dopamine in the retina. However, until recent years, there was no objective quantifiable method available to measure the association between time spent outdoors and myopia. It is only recently that the conjunctival ultraviolet autofluorescence (CUVAF) area, serving as a biomarker for sun exposure, has begun to be utilized in numerous studies. To provide a comprehensive summary of the relevant evidence pertaining to the association between the CUVAF area and myopia across different geographic regions and age groups, a systematic review and meta-analysis were conducted. The search encompassed multiple databases, including MEDLINE, SCIENCE DIRECT, GOOGLE SCHOLAR, WEB OF SCIENCE, and SCOPUS, and utilized specific search terms such as "conjunctival ultraviolet autofluorescence", "CUVAF", "UVAF", "objective marker of ocular sun exposure", "myopia", "degenerative myopia", and "high myopia". The bibliographic research included papers published between the years 2006 and 2022. A total of 4051 records were initially identified, and after duplicates were removed, 49 articles underwent full-text review. Nine articles were included in the systematic review. These studies covered myopia and outdoor exposure across different regions (Australia, Europe and India) with a total population of 3615 individuals. They found that myopes generally had smaller CUVAF areas compared to non-myopes. The meta-analysis confirmed this, revealing statistically smaller CUVAF areas in myopic patients, with a mean difference of - 3.30 mm2 (95% CI - 5.53; - 1.06). Additionally, some studies showed a positive correlation between more outdoor exposure and larger CUVAF areas. In terms of outdoor exposure time, myopic patients reported less time outdoors than non-myopic individuals, with a mean difference of - 3.38 h/week (95% CI - 4.66; - 2.09). Overall, these findings highlight the connection between outdoor exposure, CUVAF area and myopia, with regional variations playing a significant role. The results of this meta-analysis validate CUVAF as a quantitative method to objectively measure outdoor exposure in relation with myopia development.

Multimodal and longitudinal evaluation of novel phenotype-genotype correlation of CLN3 isolated retinal degeneration in an hispanic female with heterozygous mutations c.944dup and c.1305C>G.

BACKGROUND: Inherited retinal disorders (IRDs) are a complex group of heritable diseases which are characterized by rod, cone, retinal pigment epithelium, or optic nerve dysfunction. Recently, mutations in CLN3 have also been associated with isolated IRDs. Herein, a case with heterozygous CLN3 variations that had not been previously linked to a CLN3-isolated retinal degeneration (CLN3IRD) phenotype in a Hispanic female and its multimodal imaging findings across a 10-year follow-up are presented. MATERIAL AND METHODS: An observational, prospective, case report on a hispanic female with CLN3IRD is presented. Patients underwent genetic testing and color fundus photography (CFC) and autofluorescence (FAF), fluorescein angiography (FA), Spectral domain optical coherence tomography (OCT) of the macular area, electroretinogram (ERG) and 30-2 visual field examination through automated perimetry. RESULTS: A female, aged 24, affected by CLN3IRD phenotype from c.944dup and c.1305C>G compound heterozygous variants, presented with bilateral hypopigmentary changes in the macular area of OU with that corresponded to hyporautofluorescent deposits in the macular area on FAF. An atrophic maculopathy was evident on structural OCT, and FA disclosed a symmetrical macular hyperflourescence with staining in the early and late stages in OU. Humphrey visual field testing showed a marked reduction of the central visual field in OU. Electrophysiological testing revealed an ERG with markedly decreased a and b waves in OU. In ten years follow up developed of bone spiculae in the midperipheral retina. CONCLUSIONS: We reported a patient with a novel CLN3IRD severe phenotype associated with the variants c.944dup and c.1305C>G, which had previously only been associated with JCNL.

Bronchiolitis trends in out-of-hospital urgent care services in the Community of Madrid: Observational study, 2016-2023.

INTRODUCTION: Bronchiolitis poses a considerable challenge during its seasonal peak, overwhelming the material and human resources available to care for affected patients. As a result, interhospital transfers increase exponentially. We did not find any studies analysing the characteristics of patients with bronchiolitis managed in out-of-hospital urgent care (OHUC) services and the impact of the COVID-19 pandemic on the epidemiology of bronchiolitis. OBJECTIVE: To establish the characteristics of paediatric and neonatal patients with acute bronchiolitis (AB) managed in OHUC services in the Community of Madrid and to analyse the impact of the COVID-19 pandemic on the epidemiology of bronchiolitis. METHODS: Retrospective cross-sectional observational and descriptive study carried out in OHUC settings in the Community of Madrid between 2016 and 2023. We included patients with a diagnosis of acute bronchiolitis based on the ICD-10 codes documented in the electronic records of urgent care visits and interhospital transports. We collected data on sociodemographic, clinical and treatment (ventilation and medication) variables. RESULTS: The sample included 630 patients with AB: 343 managed in non-neonatal OHUC (non-neo) services and 287 by the mobile neonatal intensive care unit transport team (NTT). The median age was 3.7 months (IQR, 2.8-4.7) in patients in the non-neo OHUC group and 19 days (IQR, 14.2-23.7) in the NTT group. There was a statistically significant increase in age in the 2020/2021 season in the non-neo OHUC group. The severity score was significantly higher in the NTT group. There was an unusual peak in bronchiolitis cases in June 2021, coinciding with the end of the 4th wave of the COVID-19 pandemic. The incidence of bronchiolitis was highest after the 6th wave of the pandemic (13.5 cases per 10 000 children aged < 2 years). CONCLUSIONS: The median age of paediatric patients with AB managed in OHUC services increased following the end of the lockdown imposed due to the COVID-19 pandemic, which was probably associated with the lack of exposure to the viruses that cause it. This also may explain why the incidence of bronchiolitis was highest in the season following the 6th wave of the pandemic. The severity score was higher in neonatal patients. Epidemiological surveillance, the introduction of protocols and the implementation of an ongoing training programme for non-specialized health care staff involved in the transport of these patients could improve their management.

More than meets the eye in Parkinson's disease and other synucleinopathies: from proteinopathy to lipidopathy.

The accumulation of proteinaceous inclusions in the brain is a common feature among neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease (PD), and dementia with Lewy bodies (DLB). The main neuropathological hallmark of PD and DLB are inclusions, known as Lewy bodies (LBs), enriched not only in α-synuclein (aSyn), but also in lipid species, organelles, membranes, and even nucleic acids. Furthermore, several genetic risk factors for PD are mutations in genes involved in lipid metabolism, such as GBA1, VSP35, or PINK1. Thus, it is not surprising that mechanisms that have been implicated in PD, such as inflammation, altered intracellular and vesicular trafficking, mitochondrial dysfunction, and alterations in the protein degradation systems, may be also directly or indirectly connected through lipid homeostasis. In this review, we highlight and discuss the recent evidence that suggests lipid biology as important drivers of PD, and which require renovated attention by neuropathologists. Particularly, we address the implication of lipids in aSyn accumulation and in the spreading of aSyn pathology, in mitochondrial dysfunction, and in ER stress. Together, this suggests we should broaden the view of PD not only as a proteinopathy but also as a lipidopathy.

Validation of a Semiautomatic Optical Coherence Tomography Digital Image Processing Algorithm for Estimating the Tear Meniscus Height.

Purpose: To design and validate a high-sensitivity semiautomated algorithm, based on adaptive contrast image, able to identify and quantify tear meniscus height (TMH) from optical coherence tomography (OCT) images by using digital image processing (DIP) techniques. Methods: OCT images of the lacrimal meniscus of healthy patients and with dry eye are analyzed by our algorithm, which is composed of two stages: (1) the region of interest and (2) TMH detection and measurement. The algorithm performs an adaptive contrast sequence based on morphologic operations and derivative image intensities. Trueness, repeatability, and reproducibility for TMH measurements are computed and the algorithm performance is statistically compared against the corresponding negative obtained manually by using a commercial software. Results: The algorithm showed excellent repeatability supported by an intraclass correlation coefficient equal to 0.993, a within-subject standard deviation equal to 9.88, and a coefficient of variation equal to 2.96%, and for the reproducibility test, the results did not show a significant difference as the mean value was 244.4 ± 114.9 µm for an expert observer versus 242.4 ± 111.2 µm for the inexperienced observer (P = 0.999). The method strongly suggests the algorithm can predict measurements that are manually performed with commercial software. Conclusions: The presented algorithm possess high potential to identify and measure TMH from OCT images in a reproducible and repeatable way with minimal dependency on user. Translational Relevance: The presented work shows a methodology on how, by using DIP, it is possible to process OCT images to calculate TMH and aid ophthalmologists in the diagnosis of dry eye disease.

Applications of Infrared Thermography in Ophthalmology.

Body temperature is one of the key vital signs for determining a disease's severity, as it reflects the thermal energy generated by an individual's metabolism. Since the first study on the relationship between body temperature and diseases by Carl Reinhold August Wunderlich at the end of the 19th century, various forms of thermometers have been developed to measure body temperature. Traditionally, methods for measuring temperature can be invasive, semi-invasive, and non-invasive. In recent years, great technological advances have reduced the cost of thermographic cameras, which allowed extending their use. Thermal cameras capture the infrared radiation of the electromagnetic spectrum and process the images to represent the temperature of the object under study through a range of colors, where each color and its hue indicate a previously established temperature. Currently, cameras have a sensitivity that allows them to detect changes in temperature as small as 0.01 °C. Along with its use in other areas of medicine, thermography has been used at the ocular level for more than 50 years. In healthy subjects, the literature reports that the average corneal temperature ranges from 32.9 to 36 °C. One of the possible sources of variability in normal values is age, and other possible sources of variation are gender and external temperature. In addition to the evaluation of healthy subjects, thermography has been used to evaluate its usefulness in various eye diseases, such as Graves' orbitopathy, and tear duct obstruction for orbital diseases. The ocular surface is the most studied area. Ocular surface temperature is influenced by multiple conditions, one of the most studied being dry eye; other diseases studied include allergic conjunctivitis and pterygium as well as systemic diseases such as carotid artery stenosis. Among the corneal diseases studied are keratoconus, infectious keratitis, corneal graft rejection, the use of scleral or soft contact lenses, and the response to refractive or cataract surgery. Other diseases where thermographic features have been reported are glaucoma, diabetic retinopathy, age-related macular degeneration, retinal vascular occlusions, intraocular tumors as well as scleritis, and other inflammatory eye diseases.

Clinical outcomes of the piggyback secondary implantation of a novel multifocal lens in the ciliary sulcus: A case series.

PURPOSE: Evaluate the clinical outcomes of the secondary piggyback add-on IOL implantation in the ciliary sulcus for pseudophakic patients previously implanted with a monofocal IOL, who pursue a spectacle-free option after IOL surgery. METHODS: A prospective case series including seven pseudophakic patients who underwent an in-the-bag monofocal IOL implantation. All eyes underwent a piggyback IOL implantation of the new sulcus designed A4 AddOn IOL in the ciliary sulcus as a secondary procedure for pseudophakic patients pursuing a spectacle-free option for near and intermediate distance after IOL surgery. RESULTS: Seven eyes from six patients were included in this study, from which 4 (71.43%) were female, with a mean age of 58.33 ± 3.5 years (range 54-63; 95% CI 54.66, 62.01). The postoperative spherical equivalent at the 3-month visit was -0.10 m ± 0.82. Also, the UDVA was 0.11 ± 0.08 logMAR, the UIVA 0.01 ± 0.03, and the UNVA 0.01 ± 0.03 3 months after their surgical procedure. CONCLUSIONS: The A4 AddOn multifocal IOL's secondary piggyback implant is an efficient alternative for monofocal pseudophakic patients seeking presbyopia solutions. This sulcus-designed IOL provides an optimal visual outcome for near and distance vision.

Histones and their chaperones: Adaptive remodelers of an ever-changing chromatinic landscape.

Chromatin maintenance and remodeling are processes that take place alongside DNA repair, replication, or transcription to ensure the survival and adaptability of a cell. The environment and the needs of the cell dictate how chromatin is remodeled; particularly where and which histones are deposited, thus changing the canonical histone array to regulate chromatin structure and gene expression. Chromatin is highly dynamic, and histone variants and their chaperones play a crucial role in maintaining the epigenetic regulation at different genomic regions. Despite the large number of histone variants reported to date, studies on their roles in physiological processes and pathologies are emerging but continue to be scarce. Here, we present recent advances in the research on histone variants and their chaperones, with a focus on their importance in molecular mechanisms such as replication, transcription, and DNA damage repair. Additionally, we discuss the emerging role they have in transposable element regulation, aging, and chromatin remodeling syndromes. Finally, we describe currently used methods and their limitations in the study of these proteins and highlight the importance of improving the experimental approaches to further understand this epigenetic machinery.

Novel RB1 germline mutation in a healthy man.

BACKGROUND: Retinoblastoma (Rb) most frequently presents as a unilateral sporadic disease up to 40% of cases, however, arise from a monoallelic germline pathogenic variant. Only 10% of the germline mutations are inherited, and high penetrance is seen in up to 90% of these cases. As an effort to optimize counseling and screening, mutations are classified according to inheritance patterns. However, RB1 spectrum is highly heterogeneous, and information for unaffected carriers remains scarce. MATERIALS AND METHODS: The Mexican family of a 5-month-old patient diagnosed with Rb was studied. The family consisted of five individuals (father, mother, and three siblings). Genetic testing using a next-generation sequencing assay targeting RB1 with oligonucleotide baits designed to capture its exons and 20 bases flanking intronic sequences was performed in every family member. Clinical history and a complete ophthalmological examination (best-corrected visual acuity, slit-lamp biomicroscopy, macular optical coherence tomography, fundus autofluorescence, optical coherence tomography angiography, and electrophysiological studies) were performed in members testing positive to RB1 mutation. RESULTS: The father and her five-month-old daughter tested positive for a non-synonymous RB1 mutation c.459del (p.Lys154Serfs*21). The girl presented with bilateral retinoblastoma, successfully treated with cryotherapy and intravenous chemotherapy. The father had no relevant findings on imaging studies or ophthalmologic evaluation. CONCLUSIONS: This report describes a rare case of a novel low-penetrance RB1 germline mutation. Long-term follow-up of the father will include periodic evaluation of the eyes and orbits, and surveillance for systemic sarcoma and secondary malignancies. Implications for unaffected individuals need to be further studied.

Endogenous Levels of Alpha-Synuclein Modulate Seeding and Aggregation in Cultured Cells.

Parkinson's disease is a progressive neurodegenerative disorder characterized by the accumulation of misfolded alpha-synuclein in intraneuronal inclusions known as Lewy bodies and Lewy neurites. Multiple studies strongly implicate the levels of alpha-synuclein as a major risk factor for the onset and progression of Parkinson's disease. Alpha-synuclein pathology spreads progressively throughout interconnected brain regions but the precise molecular mechanisms underlying the seeding of alpha-synuclein aggregation are still unclear. Here, using stable cell lines expressing alpha-synuclein, we examined the correlation between endogenous alpha-synuclein levels and the seeding propensity by exogenous alpha-synuclein preformed fibrils. We applied biochemical approaches and imaging methods in stable cell lines expressing alpha-synuclein and in primary neurons to determine the impact of alpha-synuclein levels on seeding and aggregation. Our results indicate that the levels of alpha-synuclein define the pattern and severity of aggregation and the extent of p-alpha-synuclein deposition, likely explaining the selective vulnerability of different cell types in synucleinopathies. The elucidation of the cellular processes involved in the pathological aggregation of alpha-synuclein will enable the identification of novel targets and the development of therapeutic strategies for Parkinson's disease and other synucleinopathies.

Agreement between the Swept-Source Optical Coherence Tomography and the Image-Guided System for Biometry Assessment in Cataract Surgery.

PURPOSE: To assess the agreement on biometric data obtained using the Verion image-guided surgery system and the swept-source-OCT biometer IOL Master 700. MATERIALS AND METHODS: All patients underwent biometry using the SS-OCT and the Image-Guide System. The comparison between instruments was assessed using the Intraclass correlation coefficient (ICC). Level of Agreement (LoA) employing the Bland-Altman analysis. RESULTS: The image-based system produced significantly higher keratometry values, evidencing a low LoA between the SS-OCT and the image-based system, ranging from -1.30 D to 0.65 D (1.95 D), -1.04 D to 0.72 D (1.76 D), and -1.31 D to 0.65 D (1.96 D), respectively. The LoA for the Cylinder ranged from -0.46 D to 0.74 D (1.2 D) and from 0.82 to 0.94 mm for WTW. CONCLUSIONS: In our study, the SS-OCT biometer and the Image-based System evidenced statistically significant differences in measuring the main biometric parameters except for the WTW.

Comparative of meibomian gland morphology in patients with evaporative dry eye disease versus non-dry eye disease.

Many recent studies have showed that morphological changes are one of the key signs of meibomian gland disease (MGD). These changes can be seen even before symptom onset, potentially underestimating the prevalence of MGD; however, until now, there is no conclusive information about the impact of meibomian gland (MG) morphology in tear film physiology and disease. This study aimed to investigate the prevalence of anatomical and morphological MG alterations between patients with evaporative dry eye disease (DED) and healthy controls. Retrospective chart review of seventy-five patients with evaporative DED and healthy individuals who had dry eye assessments included Ocular Surface Disease Index questionnaire, meibum quality, meibum expressibility, lid margin abnormality, ocular staining, non-invasive tear film break-up time, and meibography. We did not find significant differences in MG alterations in the upper lid between healthy and DED subjects. Patients with evaporative DED presented MG alterations in the lower lid more frequently than healthy subjects (54.8 vs. 30.3%; p = 0.03). The presence of shortened glands was the only MG alteration that was more prevalent in the lower lid in dry-eye patients than in healthy subjects (p < 0.05). Subjects with evaporative DED presented more alterations in the lower lid than healthy subjects.

A methodological framework for selecting an optimal sediment source within a littoral cell.

One of the most used measures to counteract coastal erosion is beach nourishment. It has advantages with respect to the use of rigid structures that sometimes entail non desired impacts on the surrounding areas. However, beach nourishments are often unsuccessful, requiring frequent refills due to the use of sediments that are not suitable. In this paper, a methodological framework for increasing the probability of success of beach nourishment projects is presented. First, this framework consists of detecting potential borrowing areas, by analysing shoreline evolution and selecting the stretch that shows a more accretive character. Once the borrowing area has been identified, several sand extraction options are defined. The beach response (in terms of erosion and flooding) to each sand extraction alternative is analysed by using two numerical models, which simulate the hydro-morphodynamic patterns in the studied area. The numerical model results allow to find the best extraction alternative, which is that producing the least impact in the borrow area. As an example, the methodology is applied to a stretch of the Catalan coast (NW Mediterranean) to illustrate its potential. The proposed methodology shows to be a useful tool for helping coastal managers to optimize their available resources.

In silico analysis of the aggregation propensity of the SARS-CoV-2 proteome: Insight into possible cellular pathologies.

The SARS-CoV-2 virus causes the coronavirus disease 19 emerged in 2020. The pandemic triggered a turmoil in public health and is having a tremendous social and economic impact around the globe. Upon entry into host cells, the SARS-CoV-2 virus hijacks cellular machineries to produce and maintain its own proteins, spreading the infection. Although the disease is known for prominent respiratory symptoms, accumulating evidence is also demonstrating the involvement of the central nervous system, with possible mid- and long-term neurological consequences. In this study, we conducted a detailed bioinformatic analysis of the SARS-CoV-2 proteome aggregation propensity by using several complementary computational tools. Our study identified 10 aggregation prone proteins in the reference SARS-CoV-2 strain: the non-structural proteins Nsp4, Nsp6 and Nsp7 as well as ORF3a, ORF6, ORF7a, ORF7b, ORF10, CovE and CovM. By searching for the available mutants of each protein, we have found that most proteins are conserved, while ORF3a and ORF7b are variable and characterized by the occurrence of a large number of mutants with increased aggregation propensity. The geographical distribution of the mutants revealed interesting differences in the localization of aggregation-prone mutants of each protein. Aggregation-prone mutants of ORF7b were found in 7 European countries, whereas those of ORF3a in only 2. Aggregation-prone sequences of ORF7b, but not of ORF3a, were identified in Australia, India, Nepal, China, and Thailand. Our results are important for future analysis of a possible correlation between higher transmissibility and infection, as well as the presence of neurological symptoms with aggregation propensity of SARS-CoV-2 proteins.

Prevalence of Ocular Surface Disease Symptoms in High School Students in Monterrey, Mexico.

PURPOSE: To determine the prevalence of dry eye disease symptoms and contact lens wear in Mexican high school students. METHODS: A cross-sectional association study included a group of high school students who were selected from a random sampling of classrooms. The authors used the Ocular Surface Disease Index (OSDI) questionnaire as a surrogate measure for dry eye disease symptoms, and contact lens wear was also investigated. RESULTS: Seven hundred fifty-nine students with a mean age of 16.12 ± 0.96 years were surveyed and 55.7% of the students were girls (423 of 759). The average OSDI score was 25.11 ± 20.61 points. Girls had higher scores (28.25 ± 21.48 points) than boys (21.14 ± 18.74 points), and the difference was statistically significant (P < .001). Forty-three students (6.1%) wore contact lenses and had higher OSDI scores (34.26 ± 23.13 and 24.51 ± 20.31 points, respectively) and the difference was also statistically significant (P = .002). CONCLUSIONS: Symptoms of mild and moderate dry eye disease are prevalent in high school students and, as reported in previous studies, girls are more affected than boys. [J Pediatr Ophthalmol Strabismus. 2021;58(5):287-291.].

Phase 2, randomized, placebo-controlled trial of dapirolizumab pegol in patients with moderate-to-severe active systemic lupus erythematosus.

OBJECTIVE: To evaluate the dose-response, efficacy and safety of dapirolizumab pegol (DZP) in patients with SLE. METHODS: Adults with moderately to severely active SLE (SLEDAI-2K score ≥6 and ≥1 BILAG A or ≥2 BILAG B domain scores), receiving stable CS (≤40 mg/day prednisone-equivalent), antimalarial or immunosuppressant drugs were included. Patients with stable LN (proteinuria ≤2 g/day) not receiving high-dose CS or CYC were permitted entry. Randomized patients received placebo or i.v. DZP (6/24/45 mg/kg) and standard-of-care (SOC) treatment every 4 weeks to week 24, after which patients received only SOC to week 48. The primary objective was to establish a dose-response relationship based on week 24 BILAG-Based Composite Lupus Assessment (BICLA) responder rates. RESULTS: All DZP groups exhibited improvements in clinical and immunological outcomes vs placebo at week 24; however, BICLA responder rates did not fit pre-specified dose-response models [best-fitting model (Emax): P = 0.07]. Incidences of serious treatment-emergent adverse events across DZP groups were low and similar to placebo. Following DZP withdrawal, SLEDAI-2K, physician's global assessment (PGA), BILAG, and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) scores stabilized; BICLA and SLE Responder Index (SRI-4) responder rates declined (likely due to interventions with disallowed escape medications), BILAG flares increased, and immunologic parameters returned towards baseline. CONCLUSIONS: Although the primary objective was not met, DZP appeared to be well tolerated, and patients exhibited improvements across multiple clinical and immunological measures of disease activity after 24 weeks relative to placebo. The potential clinical benefit of DZP warrants further investigation.

Actividad y asistencia a la parada cardiorrespiratoria en un servicio extrahospitalario de emergencias durante la pandemia COVID-19 / Caseload and cardiopulmonary arrest management by an out-of-hospital emergency service during the COVID-19 pandemic

Objetivos. Conocer las consecuencias de la pandemia COVID-19 en la atención a la parada cardiorrespiratoria (PCR) extrahospitalaria con relación al inicio de las maniobras de resucitación cardiopulmonar (RCP) y su supervivencia. Valorar el impacto de la pandemia por COVID-19 en la actividad asistencial de un servicio de urgencias y emergencias extrahospitalarias en comparación con otros periodos sin enfermedad.Método. Estudio observacional prospectivo, basado en un registro continuo de PCR extrahospitalaria del SUMMA 112 de Madrid, durante el periodo del 1 de marzo al 30 de abril del 2020. Las variables se recogieron siguiendo las recomendaciones Utstein. Se utilizó el periodo de marzo-abril 2019 como control de comparación directa con el periodo de estudio y los periodos de enero-febrero de 2019 y de 2020 para conocer la variabilidad entre dichos años.Resultados. De las 313 PCR atendidas en marzo-abril de 2020, en 146 casos se realizó RCP avanzada. De los 87 pacientes catalogados COVID positivo, llegaron vivos al hospital 33. No se aplicaron maniobras de RCP avanzada en 167 ocasiones, identificando como causa más frecuente el tiempo de colapso excesivo. El 92,7% de las PCR sucedieron en domicilio. Comparado con otros periodos, hubo más llamadas al centro coordinador de urgencias en marzo-abril de 2020, si bien la movilización de recursos fue similar.Conclusiones. Durante la pandemia de COVID-19 hubo más mortalidad en la PCR extrahospitalaria, aumentando el porcentaje de PCR sin RCP avanzada, destacando como principal causa el tiempo de colapso excesivo. Sin embargo, aunque se incrementó significativamente la demanda telefónica, este servicio de emergencias extrahospitalarias no tuvo aumento en la movilización de los recursos móviles asistenciales. (AU)

Objective. To describe the effect of the coronavirus disease 2019 (COVID-19) pandemic on the initiation of cardiopulmonary resuscitation (CPR) in patients with out-of-hospital cardiopulmonary arrest. To compare the cardiopulmonary arrest caseload during the pandemic to the caseloads in other periods.Methods. Observational, prospective study based on the registry of out-of-hospital cardiopulmonary arrest emergencies the SUMMA112 ambulance service responded to between March 1 and April 30, 2020, in the Spanish autonomous community of Madrid. The registry is a Utstein-style database. The period of March–April 2019 was the control period for direct comparison with the 2020 study period and with the January–February periods of 2019 and 2020.Results. The responders undertook advanced CPR in 146 of the 313 cardiopulmonary arrest cases registered during March-April, 2020. Of the 87 patients with COVID-19–positive tests, 33 reached the hospital alive. Advanced CPR was not applied in 167 cases; the most frequent reason was prolonged circulatory collapse. Most cases (92.7%) occurred in the home. The emergency dispatchers received more calls in March and April of 2020, but they sent out a similar number of ambulances.Conclusions. Mortality was higher in cases of cardiopulmonary arrest during the COVID-19 pandemic. The percentage of cases with no application of advanced CPR rose; the main reason was the amount of time between collapse and first response. Even though the number of emergency calls increased significantly, the SUMMA112 service did not dispatch more ambulances. (AU)