Short-Term Efficacy of Ophthalmic Cyclosporine: A 0.1% Cationic Emulsion in Dry Eye Patients Assessed Under Controlled Environment.

INTRODUCTION: To evaluate the short-term efficacy of cyclosporine A (CsA)-0.1% cationic emulsion (CE) in patients with dry eye disease (DED) and mitigation of the inflammatory flares triggered by desiccating stress environments. METHODS: A single-center non-randomized clinical trial was performed at a tertiary care setting. Twenty patients with DED treated with CsA 0.1% CE were exposed to a normal controlled environment (NCE) (23 °C, 50% relative humidity) and an adverse controlled environment (ACE) (23 °C, 10% relative humidity, 0.43 m/s localized airflow) during baseline and the 1- and 3-month visits. Patients underwent the following evaluations: conjunctival hyperemia and staining, corneal fluorescein staining (CFS) using the Oxford and Cornea and Contact Lens Research Unit (CCLRU) scale, meibomian gland (MG) secretion quality, Dry Eye Questionnaire-5, Symptom Assessment in Dry Eye (SANDE II), and Change in Dry Eye Symptoms Questionnaire. Multivariate models were adjusted for statistical analysis. RESULTS: Nineteen women and one man (mean age, 58.9 ± 12.3 years) completed the study. All symptom questionnaires, CFS, conjunctival hyperemia and staining, and MG secretion quality improved (p ≤ 0.003) with 1 month of treatment; improvements were maintained after 3 months (p ≤ 0.02), except for SANDE II (p ≥ 0.07). The CFS worsening (total CCLRU) after baseline ACE exposure (from 8.6 to 10.1) was higher, although not significant (p = 0.64), compared with 1 month (from 5.4 to 5.8) and 3 months (from 5.0 to 5.9) after treatment. CONCLUSION: Topical CsA-0.1% CE improved DED signs and symptoms after 1 month of treatment under controlled environmental conditions. Future studies should confirm the benefit of CsA-0.1% CE in desiccating stress environments. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04492878.

Influence of controlled environmental conditions in potential salivary ocular pain biomarkers for enhancing the assessment of ocular pain.

PURPOSE: We endeavored to identify objective salivary biomarkers for pain, a subjective sensation with a biological basis, using molecules already described related to pain. The study aimed to analyze inter-individual differences and intersession variability in salivary potential ocular pain biomarkers on healthy subjects, in samples obtained under the influence of controlled environmental conditions. METHODS: Thirty-four healthy subjects, 20 male, 14 female, median age 35.44 years (range 30-40) were exposed for 30 minutes under standard environmental conditions (T: 22°C, 50% relative humidity) in the Controlled Environmental Research Laboratory (CE-Lab, Vision R&D, Valladolid Spain) in two separate visits (V1, V2) at least 24 hours apart. Saliva was collected after the exposure in each of the visits, and cortisol, α-amylase (sAA), secretory IgA (sIgA), testosterone, and soluble fraction of TNFα receptor II (sTNFαRII) were analyzed by ELISA. Repeatability of inter-subject inter-session measurements was assayed by intraclass correlation coefficient (ICC). RESULTS: There were no significant inter-session differences in testosterone (p = 0.2497), sTNFαRII (p = 0.6451) and sIgA (p = 0.9689) salivary levels. The reproducibility for salivary cortisol, sAA, testosterone, sTNFαRII and sIgA were 0.98 ng/ml, 20.58 U/ml, 21.07 µg/ml, 24.68 pg/ml and 0.19 pg/ml, respectively. Salivary cortisol, sAA, testosterone, sTNFαRII and sIgA yielded the following ICCs: 0.506, 0.569, 0.824, 0.870 and 0.4295, respectively; all these ICCs (except that for cortisol and sIgA) were found to be improved compared to those found previously by our group in a previous study in salivary samples obtained from healthy subjects under non-controlled environmental conditions; Cortisol´s ICC didn´t improve and was in both cases at the limit of acceptability. CONCLUSION: Environmental factors such as temperature and relative humidity affect the reproducibility of measurement of some salivary molecules which have been proposed as potential pain biomarkers. The exposure of subjects to standard controlled environmental conditions before salivary sample obtention would improve the reproducibility of these molecule measures' as potential biomarkers of chronic ocular pain.

Gene expression changes in conjunctival cells associated with contact lens wear and discomfort.

PURPOSE: This study aimed to analyze the differences in the expression of pain-related genes in conjunctival epithelial cells among symptomatic contact lens (CL) wearers (SCLWs), asymptomatic CL wearers (ACLWs), and non-CL wearers (non-CLWs). METHODS: For this study, 60 participants (20 non-CLWs, 40 CLWs) were enrolled. The CLW group comprised 20 ACLWs and 20 SCLWs according to the Contact Lens Dry Eye Questionnaire short form©. Conjunctival cells were collected using impression cytology, and RNA was isolated and used to determine the expression levels of 85 human genes involved in neuropathic and inflammatory pain. The effects of CL wear and discomfort were evaluated using mixed-effects ANOVA with partially nested fixed-effects model. Gene set enrichment analysis was performed to assign biological meaning to sets of differentially expressed genes. RESULTS: Six genes (CD200, EDN1, GRIN1, PTGS1, P2RX7, and TNF) were significantly upregulated in CLWs compared to non-CLWs. Eleven genes (ADORA1, BDKRB1, CACNA1B, DBH, GRIN1, GRM1, HTR1A, PDYN, PTGS1, P2RX3, and TNF) were downregulated in SCLWs compared to ACLWs. These genes were mainly related to pain, synaptic transmission and signaling, ion transport, calcium transport and concentration, and cell-cell signaling. CONCLUSIONS: CL wear modified the expression of pain- and inflammation-related genes in conjunctival epithelial cells. These changes may be in part, along with other mechanisms, responsible for CL discomfort in SCLWs.

A unique cardiac electrocardiographic 3D model. Toward interpretable AI diagnosis.

Mathematical models of cardiac electrical activity are one of the most important tools for elucidating information about heart diagnostics. In this paper, we present an efficient mathematical formulation for this modeling simple enough to be easily parameterized and rich enough to provide realistic signals. It relies on a five dipole representation of the cardiac electric source, each one associated with the well-known waves of the electrocardiogram signal. Beyond the physical basis of the model, the parameters are physiologically interpretable as they characterize the wave shape, similar to what a physician would look for in signals, thus making them very useful in diagnosis. The model accurately reproduces the electrocardiogram signals of any diseased or healthy heart. This new discovery represents a significant advance in electrocardiography research. It is especially useful for diagnosis, patient follow-up or decision-making on new therapies; is also a promising tool for well-performing, transparent and interpretable AI approaches.

Effect of a single vectored thermal pulsation treatment of Meibomian gland dysfunction patients under controlled environmental conditions.

To assess the prophylactic effect of LipiFlow treatment in Meibomian gland dysfunction (MGD) patients exposed to an adverse environmental humidity. MGD patients were exposed to normal (23 °C; 50% relative humidity; 30 min) and adverse (23 °C; 10% relative humidity; 2 h) controlled environments consecutively during baseline and follow-up visits (3, 6, and 12 months) after a single LipiFlow treatment. Ocular Surface Disease Index (OSDI), lipid layer thickness (LLT), fluorescein tear break-up time (TBUT), corneal and conjunctival staining, change in dry eye symptoms questionnaire (CDES-Q), and Meibomian gland yielding liquid secretion (MGYLS), were assessed. Linear mixed-effects and cumulative logit mixed models were fitted to assess the effect of the LipiFlow treatment over time and within the controlled environments. Seventeen females and 4 males (59.6 ± 9.4 years) completed the study. LLT and TBUT did not vary significantly (p > 0.05) after LipiFlow treatment. OSDI, corneal and conjunctival staining, and MGYLS scores were improved (p ≤ 0.01) 12 months after treatment. After the adverse exposure, corneal staining increased at all visits (p = 0.01), and there was no significant improvement in CDES-Q scores after LipiFlow treatment (p ≥ 0.07). One LipiFlow treatment improved objective and subjective outcomes in MGD disease for at least one year. Further studies are needed to support that LipiFlow might also help as an adjuvant to avoid acute flares against an adverse environmental humidity.

Phenotypic characterization of patients developing chronic dry eye and pain after refractive surgery: A cross-sectional study.

PURPOSE: To describe the clinical characteristics of patients suffering from chronic dry eye (DE) and pain after refractive surgery (RS). METHODS: Cross-sectional, observational, single-visit study. DE-, pain- and psychological-related symptoms were evaluated with specific questionnaires. DE-related tests evaluated tear osmolarity, conjunctival hyperemia, Meibomian gland dysfunction, tear stability and production, and ocular surface staining. Corneal mechanical sensitivity (Cochet-Bonnet) was measured pre/post topical anesthesia, and symptomatic variation post-anesthesia (anesthetic challenge test) was recorded. When pain was present, it was further categorized as neuropathic or nociceptive based on published criteria. RESULTS: We recruited 104 patients (39.5 ± 9.5 years). Most, 85.6%, had corneal RS as opposed to intraocular RS. Migraines, anxiety, depression (p < 0.0001), and central sensitization syndromes (p = 0.0214) were more frequent post-RS than pre-RS. Persistent DE-symptoms, severe in 86.5% patients, developed in a range of 0-204 months post-RS. Dryness and pain were the two most frequent symptoms. The only DE-related tests showing abnormal values were tear osmolarity (315.2 ± 17.1 mOsm/L; normal ≤308) and tear break-up time (4.1 ± 2.5 s; normal >7). Corneal sensitivity was 55.4 ± 7.0 mm, and decreased (p < 0.0001) after topical anesthesia, 6.0 ± 10.4 mm. However, it remained pathologically elevated, ≥10 mm in 61 (58.7%) patients. The normal symptomatic post-anesthesia improvement was absent in 58 (55.7%) patients. Ocular pain was present in 82 (78.8%) patients, and it was categorized as neuropathic in 66 (80.5%) of them, 63.5% of the entire cohort. CONCLUSIONS: Chronic ocular pain and its neuropathic subtype were diagnosed in 78.8% and 63.5% respectively of patients seeking consultation for persistent symptomatic DE post-RS.

The links among relative financial scarcity, thinking style, fatalism, and well-being.

In the present research, we examined the links among relative financial scarcity, thinking style, fatalism, and well-being and their roles in predicting protective behaviors against COVID-19. Study 1 (N = 120) revealed that after an experimental manipulation to induce the perception of relative financial scarcity (versus financial abundance), people who perceived higher relative financial scarcity changed their thinking style to a more concrete mindset. In Study 2 (N = 873), the relative financial abundance-scarcity situation was measured, and the results showed that the greater the perceived relative financial scarcity was, the more concrete the mindset and the lower the sense of well-being. Importantly, we found that individuals who felt poorer but maintained an abstract thinking style reported higher well-being. Study 3 (N = 501) examined the influence of a concrete thinking style in people who perceived that their economic situation had worsened with the pandemic. The results showed that when this vulnerable population presented a more concrete mindset, they reported lower well-being, higher fatalism, and lower protective behavior against COVID-19. Thus, maintaining an abstract mindset promotes higher well-being, lower fatalism, and greater protective behaviors against COVID-19, even under economic difficulties. Because thinking style can be modified, our results encourage the development of new social intervention programs to promote an abstract mindset when people face important challenges.

Diurnal variation on tear stability and correlation with tear cytokine concentration.

PURPOSE: To investigate the effect of time of day on tear evaporation rate (TER) and tear break-up time, and its possible relationship with the concentration of inflammatory tear molecules (cytokines) in healthy subjects. METHODS: Participants with healthy ocular surfaces attended 3 visits, including the screening visit (V0), the 2nd visit (V1) and the 3rd visit (V2). There were 7-day intervals between visits. Participants with Dry Eye Disease (DED) were excluded by using appropriate clinical tests during V0. Clinical evaluation (TER and Non-Invasive Tear Break-Up Time (NITBUT)) and tear collection were performed during V1 and V2, between 9 and 10AM and 3-4PM. The relative humidity and temperature of the examination room were also measured. The tear fluid concentrations of 15 cytokines were measured by multiplex bead analysis. RESULTS: Seven men and 10 women (mean age ± S.D; 25.1 ± 6.63 years old) participated in the study. There were no differences in neither the TER and NITBUT outcomes, nor humidity and temperature among times or visits. Eleven out of the 15 cytokines measured were detectable in tear fluids in > 50% of the participants. In the tear levels, no significant (p > 0.05) inter- and/or intra-day differences were detected for EGF, fractalkine, IL-1RA, IL-1ß and IP-10. However, significant inter-day differences were found in the tear levels of IL-10 (p = 0.027), IFN-γ (p = 0.035) and TNF-α(p = 0.04) and intra-day differences in the tear levels of IL-8/CXCL8 (p = 0.034) and MCP-1 (p = 0.002). A significant correlation between TER and IL1-ß, IL-2, and Fractalkine (p = 0.03, p = 0.03 and p = 0.046, respectively) was found at V1. CONCLUSIONS: NITBUT and TER values had no significant variability over the course of a day (AM versus PM), or on different days in healthy participants when humidity and temperature were constant. However, some tear molecule levels did show inter- and intra-day variability, having an inconsistent and moderate correlation with TER diurnal variation.

Compelling new electrocardiographic markers for automatic diagnosis.

BACKGROUND AND OBJECTIVE: The automatic diagnosis of heart diseases from the electrocardiogram (ECG) signal is crucial in clinical decision-making. However, the use of computer-based decision rules in clinical practice is still deficient, mainly due to their complexity and a lack of medical interpretation. The objetive of this research is to address these issues by providing valuable diagnostic rules that can be easily implemented in clinical practice. In this research, efficient diagnostic rules friendly in clinical practice are provided. METHODS: In this paper, interesting parameters obtained from the ECG signals analysis are presented and two simple rules for automatic diagnosis of Bundle Branch Blocks are defined using new markers derived from the so-called FMMecg delineator. The main advantages of these markers are the good statistical properties and their clear interpretation in clinically meaningful terms. RESULTS: High sensitivity and specificity values have been obtained using the proposed rules with data from more than 35,000 patients from well known benchmarking databases. In particular, to identify Complete Left Bundle Branch Blocks and differentiate this condition from subjects without heart diseases, sensitivity and specificity values ranging from 93% to 99% and from 96% to 99%, respectively. The new markers and the automatic diagnosis are easily available at https://fmmmodel.shinyapps.io/fmmEcg/, an app specifically developed for any given ECG signal. CONCLUSIONS: The proposal is different from others in the literature and it is compelling for three main reasons. On the one hand, the markers have a concise electrocardiographic interpretation. On the other hand, the diagnosis rules have a very high accuracy. Finally, the markers can be provided by any device that registers the ECG signal and the automatic diagnosis is made straightforwardly, in contrast to the black-box and deep learning algorithms.

EVO+ Implantable Collamer Lens KS-aquaPORT Location, Stability, and Impact on Quality of Vision and Life.

PURPOSE: To determine the longitudinal variation in the KS-aquaPORT central hole location of the phakic EVO+I Implantable Collamer Lens (ICL) (STAAR Surgical) and analyze its influence on visual performance, quality of vision (QoV), and quality of life (QoL). METHODS: A prospective study was performed including 36 patients who had EVO+ ICL implantation. The KS-aquaPORT central hole location (Cartesian and polar coordinates) was determined with respect to the pupil center and visual axis. The effect of time (6-month follow-up) on central hole location was analyzed using linear mixed models. The effect of the KS-aquaPORT location on visual performance, QoV, and QoL parameters was assessed with multivariate regression models. RESULTS: With respect to the visual axis, no significant changes in KS-aquaPORT location were found during follow-up. With respect to the pupil center, the X-coordinate and radius of KS-aquaPORT location showed modest, but significant (P ≤ .05) differences between 1-week and 3-month postoperative visits, and between 1-week and 6-month visits. X-coordinate variation was significant (P = .022) between 1-and 6-month visits. With respect to the visual axis, greater KS-aquaPORT decentration was associated with worse visual acuity (X-coordinate: P = .004; radius: P = .006), and inferior decentration with longer xenon-type glare photostress recovery time (P = .021). With respect to the pupil center, a lower radius was associated with better QoV scores (P ≤ .01) and temporal decentration produced higher ring-shaped dysphotopsia (P = .007). CONCLUSIONS: EVO+ ICL KS-aquaPORT location appears to be clinically stable up to 6 months postoperatively. A central location of the EVO+ ICL KS-aquaPORT hole is preferred because it allows reduced perception of dysphotopic phenomena that can result in better QoV. [J Refract Surg. 2022;38(3):177-183.].

Inflammation-related molecules in tears of patients with chronic ocular pain and dry eye disease.

The purpose of this study was to analyze inflammation- and pain-related molecules in tears of patients suffering from chronic ocular pain associated with dry eye (DE) and/or a previous corneal refractive surgery (RS). Based on history, symptomatology, and clinical signs, the subjects (n = 180, 51.0 ± 14.7 years, 118 females, 62 males) in this cross-sectional study were assigned to one of five groups: DE and chronic ocular pain after RS (P/DE-RS, n = 52); asymptomatic subjects, i.e., without DE and chronic ocular pain, after RS (A-RS, n = 30); DE and chronic ocular pain without previous RS (P/DE-nonRS, n = 31); DE, no pain, and no previous RS (DE-nonRS, n = 35); and asymptomatic subjects with no previous RS (controls, n = 32). The tear concentrations of 20 cytokines and substance P (SP) were analyzed by immunobead-based assay and enzyme-linked immunosorbent assay, respectively. We found that tear levels of interleukin (IL)-10 and SP were increased in the RS groups. There were significant differences in IL-8/CXCL8 among the five groups. Nerve growth factor (NGF) tear levels were significantly higher in P/DE-RS than in DE-nonRS and controls. IL-9 had the highest percentage of detection in the P/DE-RS and P/DE-nonRS groups, while macrophage inflammatory protein (MIP)-1α, IL-2, and interferon (IFN)-γ were higher in the P/DE-RS, A-RS, and P/DE-nonRS groups. IL-17A was detected only in the A-RS group. Moderate correlations were observed in the A-RS, P/DE-nonRS, DE-nonRS and controls groups. A positive correlation was obtained between growth related oncogene concentration and tear break-up time (rho = 0.550; p = 0.012), while negative correlation was found between monocyte chemoattractant protein-3/CCL7 and conjunctival staining (rho = -0.560; p = 0.001), both in the A-RS group. IL-10 correlated positively with ocular pain intensity (rho = 0.513; p = 0.003) in the P/DE-nonRS group. Regulated on Activation Normal T Cell Expressed and Secreted/CCL5 correlated negatively with conjunctival staining (rho = -0.545; p = 0.001) in the DE-nonRS group. SP correlated negatively with corneal staining (rho = -0.559; p = 0.001) in the controls. In conclusion, chronic ocular pain was associated with higher IL-9 tear levels. IL-10, SP, MIP-1α/CCL3, IL-2, and IFN-γ were associated with previous RS. Higher levels of IL-8/CXCL8, MIP-1α/CCL3, IL-2, and IFN-γ were associated with DE-related inflammation, while NGF levels were related to chronic ocular pain and DE in RS patients. These findings suggest that improved knowledge of tear cytokines and neuromodulators will lead to a more nuanced understanding of how these molecules can serve as biomarkers of chronic ocular pain, leading to better therapeutic and disease management decisions.

Disentangling Emotions during the Coronavirus Outbreak in Spain: Inner Emotions, Descriptive Feeling Rules and Socioemotional Conventions.

For constructionism, language is the link among different levels of analysis of emotional events, from individual to interpersonal and macrosocial. The interaction among these emotional levels allows us to construe an emotional episode and label it with an emotion word, coordinate with the emotions perceived in others, and represent events as a society. Across two studies, we found similarities and differences among inner emotions experienced (individual level), emotions perceived in others (descriptive feeling rules, interpersonal level) and emotions shared on the internet (socioemotional conventions, macrosocial level), with all these emotional targets focused on the COVID-19 outbreak. The results indicate a similarity between the emotional meaning of COVID-19 in society and the descriptive feeling rules, whereas the reported inner emotions were clearly distinct: Joy was irrelevant at the interpersonal and macrosocial levels but clearly important at the individual level. A mismatch also appeared for fear and hope. While fear was the most predominant emotion at the interpersonal and macrosocial levels during most of the phases, it was moderately predominant at the individual level. Hope followed the opposite pattern, being the most relevant emotion at the individual level but less relevant at the interpersonal and macrosocial levels. Each level might have different consequences: Mixed emotions at the individual level might promote resilience; fear perceived in other people might motivate protective behaviors; and sadness socially shared during Christmas might generate greater empathy. These results support the complexity of emotional concepts and the suitability of exploring them at different levels of analysis.

Disentangling Emotions during the Coronavirus Outbreak in Spain: Inner Emotions, Descriptive Feeling Rules and Socioemotional Conventions

For constructionism, language is the link among different levels of analysis of emotional events, from individual to interpersonal and macrosocial. The interaction among these emotional levels allows us to construe an emotional episode and label it with an emotion word, coordinate with the emotions perceived in others, and represent events as a society. Across two studies, we found similarities and differences among inner emotions experienced (individual level), emotions perceived in others (descriptive feeling rules, interpersonal level) and emotions shared on the internet (socioemotional conventions, macrosocial level), with all these emotional targets focused on the COVID–19 outbreak. The results indicate a similarity between the emotional meaning of COVID–19 in society and the descriptive feeling rules, whereas the reported inner emotions were clearly distinct: Joy was irrelevant at the interpersonal and macrosocial levels but clearly important at the individual level. A mismatch also appeared for fear and hope. While fear was the most predominant emotion at the interpersonal and macrosocial levels during most of the phases, it was moderately predominant at the individual level. Hope followed the opposite pattern, being the most relevant emotion at the individual level but less relevant at the interpersonal and macrosocial levels. Each level might have different consequences: Mixed emotions at the individual level might promote resilience; fear perceived in other people might motivate protective behaviors; and sadness socially shared during Christmas might generate greater empathy. These results support the complexity of emotional concepts and the suitability of exploring them at different levels of analysis. (AU)

Design of a questionnaire for detecting contact lens discomfort: the Contact Lens Discomfort Index.

CLINICAL RELEVANCE: Questionnaires can provide unique information regarding the status of a condition from the perspective of the patient. Contact lens (CL) discomfort (CLD) is a condition subjectively reported by CL users; thus, updated and reliable questionnaires are needed. BACKGROUND: The objective of this study was to design a new questionnaire for identifying CLD, based on the currently established CLD definition considered in the Tear Film and Ocular Surface CLD Workshop. METHODS: A survey to characterise CL wearers was created and administered. Some items of the survey were selected by a focus group and analysed using a Rasch model to develop a questionnaire to identify CLD. Unidimensionality was checked applying principal components analysis. To build a plausible CLD classification (symptomatic vs asymptomatic), an unsupervised cluster analysis was used. Gower's general similarity coefficient, the partitioning around medoids algorithm, and the silhouette width were calculated. The reliability of the questionnaire was assessed using the intraclass correlation coefficient and Cohen's kappa coefficient. A study was performed to compare this questionnaire with the Contact Lens Dry Eye Questionnaire (CLDEQ)-8. RESULTS: The 31-item survey was completed by 1104 volunteers, and the posterior analysis resulted in a 9-item questionnaire, the Contact Lens Discomfort Index (CLDI). It showed a good fit with the model (mean square infit and outfit values range was 0.76-1.10), and good unidimensionality (eigenvalues ≤ 1.3). The CLDI score range was 0-18 and the cut-off score for identifying CLD was 8. The intraclass correlation coefficient was 0.88 (95% confidence interval, 0.75-0.94), and kappa was 0.67 (95% confidence interval, 0.41-0.93). Comparison of the CLDI with the CLDEQ-8 in a sample of 58 CL wearers showed that 70.7% were classified equally by both questionnaires. CONCLUSIONS: The CLDI is a well-structured instrument, with acceptable psychometric properties, making it a valid and reliable tool to measure CL-related symptoms.

Can the Cytokine Profile According to ABO Blood Groups Be Related to Worse Outcome in COVID-19 Patients? Yes, They Can.

Severe status of coronavirus disease 2019 (COVID-19) is extremely associated to cytokine release. Moreover, it has been suggested that blood group is also associated with the prevalence and severity of this disease. However, the relationship between the cytokine profile and blood group remains unclear in COVID-19 patients. In this sense, we prospectively recruited 108 COVID-19 patients between March and April 2020 and divided according to ABO blood group. For the analysis of 45 cytokines, plasma samples were collected in the time of admission to hospital ward or intensive care unit and at the sixth day after hospital admission. The results show that there was a risk of more than two times lower of mechanical ventilation or death in patients with blood group O (log rank: p = 0.042). At first time, all statistically significant cytokine levels, except from hepatocyte growth factor, were higher in O blood group patients meanwhile the second time showed a significant drop, between 20% and 40%. In contrast, A/B/AB group presented a maintenance of cytokine levels during time. Hepatocyte growth factor showed a significant association with intubation or mortality risk in non-O blood group patients (OR: 4.229, 95% CI (2.064-8.665), p < 0.001) and also was the only one bad prognosis biomarker in O blood group patients (OR: 8.852, 95% CI (1.540-50.878), p = 0.015). Therefore, higher cytokine levels in O blood group are associated with a better outcome than A/B/AB group in COVID-19 patients.

Long-term visual pathway alterations after elemental mercury poisoning: report of a series of 29 cases.

BACKGROUND: There are few clinical data on retinal involvement after acute exposure to high concentrations mercury and the available reports are based on a small number of patients suffering chronic exposure. The purpose of this paper is to report findings in workers acutely exposed to very high concentrations of mercury vapor with the aim of providing data on a possible direct retinal involvement. METHODS: Twenty-nine patients and 16 controls were evaluated in a comparative case series. Mercury levels in blood and urine samples, visual acuity (VA), contrast sensitivity (CS), visual field (VF), color discrimination and optical coherence tomography (OCT) were recorded. The pattern reversal visual-evoked potentials (PRVEP), full-field and multifocal electroretinography (ffERG/mfERG), pattern electroretinography (PERG), systemic symptoms, presence of erethism, and electromyography (EMG) were also gathered. A descriptive analysis was performed. The correlations between variables also were studied. In addition, electrophysiological data from those patients with deeper VF defects (group 1) were compared with a normal control group. RESULTS: Twenty-six workers exhibited symptoms of erethism. The EMG showed sensorimotor polyneuropathy and multiple mononeuropathy. The VA was slightly affected in 48.27% (n = 14) of subjects. Loss of CS in at least one of four spatial frequencies and color vision alterations occurred in 96.5% (n = 28) and 44.8% (n = 13), respectively. VF alterations were identified in 72.4% (n = 21) patients. No morphologic changes were seen in the OCT scans. Latencies over 100 milliseconds and reduced amplitudes of P100 were found in the PRVEP (p < 0.05). The reduced amplitude of the b wave at the ffERG, of the P50 at the PERG and of the P1 wave at the mfERG results (p < 0.05) suggested that the outer retina was involved. Significant negative correlations among blood mercury levels, VA, and ffERG were observed. CONCLUSIONS: In this case series, showed that acute exposure to mercury vapor had a hazardous effect on the visual system. Although neurologic and visual pathway involvement was clearly demonstrated, the differences found compared to control support the existence of a direct functional retinal damage and participation in impaired vision in mercury poisoning.

Epithelial component and intraepithelial lymphocytes of conjunctiva-associated lymphoid tissue in healthy children.

Conjunctiva-associated lymphoid tissue (CALT) plays a key role in protecting the eye surface by initiating and regulating immune responses. The aim of this study was to investigate in healthy children the proportion of intraepithelial lymphocytes (IELs), the degree of viability and/or apoptosis and cell proliferation in three different topographic areas of the conjunctiva. Superior tarsal, superior bulbar, and inferior tarsal-bulbarfornix conjunctival cells were collected by brush cytology (BC) from 24 healthy paediatric subjects (13 boys and 11 girls, mean age 6±2 years) who were to undergo strabismus correction surgery under general anaesthesia. Subsequently, these cells were analysed phenotypically and functionally by flow cytometry (FC). Flow cytometry analysis showed that not all the cells obtained by BC were of the epithelial lineage, but that there was a population of CD45+ cells (IELs) regularly present in the conjunctiva of healthy children. These IELs were mostly T-lymphocytes (CD3+) and B-lymphocytes (CD19+), with higher levels of T-lymphocytes (CD3+) in the upper areas than in the inferior tarsal-bulbar-fornix, where the highest levels of B-lymphocytes (CD19+) were found. In the apoptosis assay, two groups of cell populations were differentiated by cell size and complexity (cytoplasmic granularity), with more complex cells predominating in the upper areas of the conjunctiva and less complex cells being more abundant in the inferior tarsal-bulbar-fornix. Finally, the proliferative capacity of the conjunctival epithelium was significantly higher in the upper tarsal zone than in the rest of the zones analysed. These results suggest that the epithelial component and the IELs of CALT are also regularly present in the conjunctiva of the healthy child, varying in phenotype, viability and cell proliferation according to the different conjunctival regions analysed, which could lead us to believe that each conjunctival zone plays a different, specific role in the regulation of the immune response at the ocular level.

Self-Transcendent Emotions and Their Social Effects: Awe, Elevation and Kama Muta Promote a Human Identification and Motivations to Help Others.

Abundant literature shows the effects of negative emotions on motivations to engage in collective action (i.e., to collectively mobilize personal resources to achieve a common objective), as well as their influence on the creation of shared identities. In this proposal, we focus on the possible role of Self-Transcendent Emotions (STEs) defined as positive-valence emotions that have been key in the creation and maintenance of collective identities, as well as in promoting individuals well-being. In detail, we examine their influence in (a) strengthening a global identification, (b) increasing willingness to collectively help others, and (c) improving people's wellbeing. For this reason, we conducted a preliminary literature review of k = 65 independent studies on the effects of STEs on connection to others. Through this review (fully available in Supplementary Materials), we selected a sample of STEs (Awe, Elevation, and Kama Muta) and elicitors to conduct a video-base study. In it, 1,064 university students from 3 different cultural regions (from Spain and Ecuador) were randomized to answer one of three STE scales (i.e., each measuring one of the selected STEs), and evaluate three videos in random order (i.e., each prototypical for the selected STEs). Participants also answered a measure of global identification and intentions to collectively help others (after each video), as well as self-transcendent and well-being (at the end of the survey). Results from SEM analyses show these STEs motivated a fusion of identity with all humanity, as well as collective intentions to help others, even controlling for individuals' value orientations. In addition, the three of them indirectly increased participants' well-being through a higher global identity. While there are differences among them, these three STEs share common elements and their effects are constant across the different cultural regions. It is concluded that Awe, Elevation, and Kama Muta, even individually experienced, have a significant potential to influence people's behavior. Specifically, in various forms of collective action aimed at helping others.