Evaluation of different glycerol fed-batch strategies in a lab-scale bioreactor for the improved production of a novel engineered ß-fructofuranosidase enzyme in Pichia pastoris.

The ß-fructofuranosidase enzyme from Aspergillus niger has been extensively used to commercially produce fructooligosaccharides from sucrose. In this study, the native and an engineered version of the ß-fructofuranosidase enzyme were expressed in Pichia pastoris under control of the glyceraldehyde-3-phosphate dehydrogenase promoter, and production was evaluated in bioreactors using either dissolved oxygen (DO-stat) or constant feed fed-batch feeding strategies. The DO-stat cultivations produced lower biomass concentrations but this resulted in higher volumetric activity for both strains. The native enzyme produced the highest volumetric enzyme activity for both feeding strategies (20.8% and 13.5% higher than that achieved by the engineered enzyme, for DO-stat and constant feed, respectively). However, the constant feed cultivations produced higher biomass concentrations and higher volumetric productivity for both the native as well as engineered enzymes due to shorter process time requirements (59 h for constant feed and 155 h for DO-stat feed). Despite the DO-stat feeding strategy achieving a higher maximum enzyme activity, the constant feed strategy would be preferred for production of the ß-fructofuranosidase enzyme using glycerol due to the many industrial advantages related to its enhanced volumetric enzyme productivity.

Applicability of an unsupervised cluster model developed on first wave COVID-19 patients in second/third wave critically ill patients.

OBJECTIVE: To validate the unsupervised cluster model (USCM) developed during the first pandemic wave in a cohort of critically ill patients from the second and third pandemic waves. DESIGN: Observational, retrospective, multicentre study. SETTING: Intensive Care Unit (ICU). PATIENTS: Adult patients admitted with COVID-19 and respiratory failure during the second and third pandemic waves. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Collected data included demographic and clinical characteristics, comorbidities, laboratory tests and ICU outcomes. To validate our original USCM, we assigned a phenotype to each patient of the validation cohort. The performance of the classification was determined by Silhouette coefficient (SC) and general linear modelling. In a post-hoc analysis we developed and validated a USCM specific to the validation set. The model's performance was measured using accuracy test and area under curve (AUC) ROC. RESULTS: A total of 2330 patients (mean age 63 [53-82] years, 1643 (70.5%) male, median APACHE II score (12 [9-16]) and SOFA score (4 [3-6]) were included. The ICU mortality was 27.2%. The USCM classified patients into 3 clinical phenotypes: A (n = 1206 patients, 51.8%); B (n = 618 patients, 26.5%), and C (n = 506 patients, 21.7%). The characteristics of patients within each phenotype were significantly different from the original population. The SC was -0.007 and the inclusion of phenotype classification in a regression model did not improve the model performance (0.79 and 0.78 ROC for original and validation model). The post-hoc model performed better than the validation model (SC -0.08). CONCLUSION: Models developed using machine learning techniques during the first pandemic wave cannot be applied with adequate performance to patients admitted in subsequent waves without prior validation.

Congruencia Diagnóstica Clínica-Histopatológica de Lesiones en Cavidad Oral, en la Faculta de Odontología, Universidad de Costa Rica, en el Período 2016-2019

El conocimiento de la patología oral, y su correcto diagnóstico es fundamental en Odontología, puesto que un diagnóstico tardío, particularmente en casos de lesiones premalignas o malignas, pueden conducir a serias consecuencias para el paciente. El objetivo de este trabajo fue establecer la congruencia diagnóstica clínica - histopatológica de lesiones en cavidad oral en pacientes que asistieron a la Facultad de Odontología, Universidad de Costa Rica, y a quienes se les realizó biopsia de la lesión, durante el período 2016-2019. El estudio fue descriptivo y retrospectivo, basado en datos de reportes histopatológicos en la población mencionada, por presentar alguna lesión, de tejidos blandos o duros, en cavidad oral. La muestra estadística fue por conveniencia, no probabilística y no aleatoria. Las técnicas estadísticas utilizadas fueron descriptivas para el análisis de la información, el cual se basó en la distribución de frecuencias y cruce de variables. El procesamiento estadístico de los datos se diseñó en una base de datos creada en Excel. La muestra comprendió 160 reportes histopatológicos de los cuales se excluyeron 14. La edad promedio de los pacientes fue 42 años (rango 2 - 78 años). La proporción hombre: mujer correspondió 1:1.4, predominado el sexo femenino en 58,9 %. La congruencia del diagnóstico histopatológico con el diagnóstico clínico correspondió a 55,8 %. La congruencia de los diagnósticos demuestra el conocimiento del profesional en identificar la lesión clínicamente de forma correcta, lo que permite actuar en el momento preciso y confirmar la impresión clínica diagnóstica de una patología mediante el estudio histopatológico, el cual es el estándar oro. El problema radica en aquellos casos en que hay discrepancia diagnóstica, pues exige conocer los factores responsables de esta discrepancia, exige la búsqueda de soluciones y exige reforzar y redireccionar la formación académica del profesional y de los estudiantes para reconocer y describir estas lesiones.

Knowledge of oral pathology and its correct diagnosis is fundamental in Dentistry, since a late diagnosis, particularly in cases of premalignant or malignant lesions, can lead to serious consequences for the patient. The objective of this study was to establish the clinical- histopathological diagnostic consistency of lesions in the oral cavity in patients who attended the Faculty of Dentistry, Universidad de Costa Rica, and who underwent a biopsy of the lesion, during the period 2016-2019. The study was descriptive and retrospective, based on data from histopathological reports in the mentioned population, due to presenting some lesion, soft or hard tissue, in the oral cavity. The statistical sample was for convenience, non- probabilistic nor random. The statistical techniques used were descriptive for the analysis of the information, which was based on frequency distribution and crossing of variables. The statistical processing of the data was designed in a database created in Excel. The sample collects 160 histopathological reports, of which 14 were excluded. The average age of the patients was 42 years (range between 2 - 78 years old).The male:female ratio corresponded to 1:1.4, with a predominance of the female sex at 58.9 %.The congruence of the histopathological diagnosis with the clinical diagnosis corresponded to 55.8 %. Diagnostic consistency demonstrates knowledge of the professional in correctly identifying the lesion clinically, which allows acting at the precise moment and confirming the diagnostic clinical impression of the pathology via histopathological study which is the gold standard. The problem lies in those cases in which there is a diagnostic discrepancy, since it requires having knowledge of the underlying factors and therefore, requires searching for solutions, reinforcing and redirecting the academic training of professionals and students to recognize and describe these lesions.

Validation of a 3D Local-Scale Adaptive Solar Radiation Model by Using Pyranometer Measurements and a High-Resolution Digital Elevation Model.

The result of the multidisciplinary collaboration of researchers from different areas of knowledge to validate a solar radiation model is presented. The MAPsol is a 3D local-scale adaptive solar radiation model that allows us to estimate direct, diffuse, and reflected irradiance for clear sky conditions. The model includes the adaptation of the mesh to complex orography and albedo, and considers the shadows cast by the terrain and buildings. The surface mesh generation is based on surface refinement, smoothing and parameterization techniques and allows the generation of high-quality adapted meshes with a reasonable number of elements. Another key aspect of the paper is the generation of a high-resolution digital elevation model (DEM). This high-resolution DEM is constructed from LiDAR data, and its resolution is two times more accurate than the publicly available DEMs. The validation process uses direct and global solar irradiance data obtained from pyranometers at the University of Salamanca located in an urban area affected by systematic shading from nearby buildings. This work provides an efficient protocol for studying solar resources, with particular emphasis on areas of complex orography and dense buildings where shadows can potentially make solar energy production facilities less efficient.

Unlocking peach juice byproduct potential in food waste biorefineries: Phenolic compounds profile, antioxidant capacity and fermentable sugars.

This work assesses an integrated pathway for the revalorization of peach byproduct (PB) within a biorefinery. PB was subjected to an oven-drying (OD) treatment for its evaluation as a storage treatment. It was compared to freeze-drying and untreated material in terms of antioxidant capacity (AOC), phenolic compounds (PC) profile and fermentable sugar production. OD reduced the water content to less than 15 % while preserving the bound hydrolysable polyphenols, which were the more abundant PC (≈64 %) with the highest AOC. Drying treatments hampered polysaccharide accessibility, but some enzyme preparations released 60-70 g/L of fermentable sugars at relatively high solids loading (10 %). This study proposes a novel enzyme-based strategy for the valorisation of fermentable sugars and antioxidant compounds from PB. The sugars can be fermented into several building blocks while the solid residue enriched in recalcitrant phenolic compounds and proteins could be used to develop novel functional products for food/feed sectors.

Docetaxel Provides Oncological Benefits in the Era of New-Generation Androgen Receptor Inhibitors - or Is Three a Crowd?

In recent years, several systemic therapies have been introduced for metastatic hormone-sensitive prostate cancer, including androgen deprivation therapy (ADT) combined with docetaxel (Doc) and/or new-generation androgen receptor signaling inhibitors (ARSI). Trials evaluating ADT + ARSI have consistently demonstrated an overall survival (OS) benefit for doublet therapy over ADT alone. Similarly, the STOPCaP meta-analysis showed an OS benefit in favor of ADT + Doc versus ADT alone. ARSI, Doc, and ADT have different antitumor mechanisms, thus potentiating the effect of combination therapy. Two randomized trials showed that the addition of ARSI to ADT + Doc improves OS, especially for synchronous high-volume disease. However, the real question about triplet therapy remains unanswered: whether combining Doc with ARSI improves outcomes compared to ADT + ARSI. As there are no head-to-head comparisons, this narrative review aims to summarize the current evidence regarding triplet therapy versus doublet therapy including ADT+ ARSI.

Novel Approaches in the Systemic Management of High-Risk Prostate Cancer.

Locally advanced prostate cancer comprises approximately 20% of new prostate cancer diagnoses. For these patients, international guidelines recommend treatment with radiotherapy (RT) to the prostate in combination with long-term (2-3 years) androgen deprivation therapy (ADT), or radical prostatectomy in combination with extended pelvic lymph node dissection (PLND) as another treatment option for selected patients as part of multimodal therapy. Improvements in overall survival with docetaxel or an androgen receptor signaling inhibitor have been achieved in patients with metastatic castration sensitive or castration resistant prostate cancer. However, the role of systemic therapy combinations for high risk and/or unfavorable prostate cancer is unclear. In this context, the aim of this review is to assess the current evidence for systemic treatment combinations as part of primary definitive therapy in patients with high-risk localized prostate cancer.

Food Knowledge for Better Nutrition and Health: A Study among University Students in Portugal.

When students enter university, they suffer adaptations, including, usually, greater autonomy and responsibility for the choices they make. Therefore, it is crucial that they are well informed so as to make healthier food choices. The aim of this study was to determine whether sociodemographic characteristics, academic performance and lifestyle (tobacco and alcohol consumption) interfere with food literacy in university students. A quantitative, analytical, descriptive, transversal and correlational study was carried out, using quantitative data obtained through a questionnaire survey applied to a sample of 924 university students in Portugal. Food literacy was assessed through a scale of 27 items, distributed in three dimensions: D1-Literacy about food nutritional value and composition, D2-Literacy about labelling and food choice and D3-Literacy about healthy eating practices. Results showed no differences in food literacy according to sex or age. However, food literacy varied significantly with nationality, either globally (p = 0.006) or in the different dimensions evaluated (p-values of 0.005, 0.027 and 0.012 for D1, D2 and D3, respectively). In terms of academic achievement, the results showed no significant differences according to self-reported academic performance or even to the average classification obtained in the course. Regarding lifestyle variables, it was observed that alcohol consumption or smoking are not associated with food literacy, that is, food literacy does not vary significantly with these two lifestyle variables. In conclusion, food literacy in general and the dimensions evaluated are essentially constant among university students in Portugal, only varying for students from abroad. These results help to better perceive the food literacy levels for the population under study, university students, and that can be a valuable tool to better increase food literacy at these institutions as a way to better prepare for a healthier life and proper food habits that can enhance health in the long term.

Neurocognitive Suicide and Homicide Markers in Patients with Schizophrenia Spectrum Disorders: A Systematic Review.

Suicide and homicide are considered important problems in public health. This study aims to identify the cognitive performance of suicidal and homicidal behaviors in people with schizophrenia spectrum disorders, as well as examining whether there are shared neuropsychological mechanisms. A systematic review of the recent literature was carried out from September 2012 to June 2022 using the Medline (via PubMed), Scopus, Embase, and Cochrane databases. Among the 870 studies initially identified, 23 were finally selected (15 related to suicidal behaviors and 8 to homicidal behaviors). The results evidenced a relationship between impairment of cognitive performance and homicidal behavior; meanwhile, for suicidal behaviors, no consistent results were found. High neuropsychological performance seems to act as a protective factor against violent behavior in people with schizophrenia spectrum disorders, but not against suicidal behavior; indeed, it can even act as a risk factor for suicidal behavior. To date, there is insufficient evidence that shared neurocognitive mechanisms exist. However, processing speed and visual memory seem to be affected in the presence of both behaviors.

Effectiveness of nontechnical skills educational interventions in the context of emergencies: A systematic review and meta-analysis.

INTRODUCTION: In recent years, the importance of training healthcare professionals in nontechnical skills using effective methodologies has been increasingly recognised as a means of preventing clinical errors in the practice of health care. The aim of this study was to evaluate the effectiveness of educational interventions on nontechnical skills in the emergency medical services and/or critical care unit settings. METHODS: A systematic search was carried out in the PubMed, SCOPUS, CINAHL, and Web of Science databases according to predetermined inclusion and exclusion criteria. After the initial search, 7952 records were selected after duplicates removed. Finally, a selection of 38 studies was included for quantitative analysis. Separate meta-analyses of standardised mean changes were carried out for each outcome measure assuming a random-effects model. Cochran's Q-statistic and I2 index were applied to verify study heterogeneity. Weighted analyses of variance and meta-regressions were conducted to test the influence of potential moderators and funnel plots using Duval and Tweedie's trim-and-fill method, and Egger's regression test were used to examine publication bias. RESULTS: All the variables analysed had a significant effect size, with the exception of situational awareness (d+ = -0.448; 95% confidence interval [CI] = -1.034, 0.139). The highest mean effect size was found for knowledge (d+ = -0.925; 95% CI = -1.177, -0.673), followed by the mean effect sizes for global nontechnical skills (d+ = -0.642; 95% CI = -0.849, -0.434), team nontechnical skills (d+ = -0.606; 95% CI = -0.949, -0.262), and leadership nontechnical skills (d+ = -0.571; 95% CI = -0.877, -0.264). Similar mean effect sizes were found for attitude (d+ = -0.406; 95% CI = -0.769, -0.044), self-efficacy (d+ = -0.469; 95% CI = -0.874, -0.064), and communication nontechnical skills (d+ = -0.458; 95% CI = -0.818, -0.099). Large heterogeneity among the standardised mean changes was found in the meta-analyses (I2 > 75% and p < .001), except for self-efficacy where I2 = 58.17%, and there was a nonstatistical result for Cochran's Q. This great variability is also reflected in the forest plots. DISCUSSION: The use of simulation interventions to train emergency and critical care healthcare professionals in nontechnical skills significantly improves levels of knowledge, attitude, self-efficacy, and nontechnical skills performance.

Benign osteoblastoma of the mandible: a case report.

Osteoblastoma is a rare benign neoplasm formed by osteoid tissue and well-vascularized bone that occurs mainly in children and adolescents. It appears primarily in the long bones, vertebral column, and small bones of the hands and feet, and not typically in the skull and maxillary bones. The purpose of this study is to present the case of an 8-year-old girl with a diagnosis of right mandibular osteoblastoma and a review of the relevant literature. The goals of treatment were to preserve dental occlusion, masticatory function and facial symmetry while minimizing the effects on patient body image and quality of life. Osteoblastoma, although it is benign, can be aggressive, and its treatment will depend on the timing of diagnosis, size and location. Early diagnosis is essential to avoid not only radical surgery as in the case presented, but also to help minimize the risk of possible relapse and potential malignancy of a benign osteoblastoma.

A reflection on the essence of gratitude in palliative care: healing in severe disease and professional affirmation through accompanying patients until the end.

Background: Gratitude has sparked interest in the world of health. It is considered as a personality characteristic or as an emotion. However, little has been explored in the context of the interpersonal relationship of caring. An exploration in the context of end of life is ground-breaking. Objectives: This study analyses and reflects on the object of gratitude from the perspective of both the persons being cared for and the professionals providing health care. What are patients and their family members grateful for in palliative care? What is the reason for gratitude? What do these health professionals perceive when there is gratitude? These questions were answered considering the gratitude generated in health care encounters, not gratitude as personality trait. Methods: The phenomenological approach was used starting from lived clinical experiences. In the light of the dialogue between clinical experiences and philosophy, this study proposes an explanation of the 'real' or essential object of gratitude in palliative care. It was conducted within the context of palliative care. The study materials were manifestations of gratitude expressed or felt in clinical encounters and published in newspapers or shared in daily encounters. These were the basis for analysis and reflection and interdisciplinary dialogue. Findings: The analyses performed indicated healing or deep relief in serious diseases as objects of gratitude according to patients' perspective, and professional self-affirmation until the end according to the professionals' perspective. Conclusion: The two perspectives shared an important common fact, namely, the need to consider the persons in their entirety, and the importance of not losing sight of the value they have. This concept would characterize the nature of gratitude, its object being the 'objective good' for patients, family members, and palliative care professionals.

Real-life outcomes in biotypes of psychotic disorders based on neurocognitive performance.

Aiming at discerning potential biotypes within the psychotic syndrome, we have recently reported the possible existence of two clusters or biotypes across schizophrenia and bipolar disorder characterized by their cognitive performance using the Brief Assessment of Cognition in Schizophrenia (BACS) instrument and validated with independent biological and clinical indexes (Fernández-Linsenbarth et al. in Schizophr Res 229:102-111, 2021). In this previous work, the group with larger cognitive deficits (N = 93, including 69 chronic schizophrenia, 17 first episodes (FE) of schizophrenia and 7 bipolar disorder patients) showed smaller thalamus and hippocampus volume and hyper-synchronic electroencephalogram than the group with milder deficits (N = 105, including 58 chronic schizophrenia, 25 FE and 22 bipolar disorder patients). We predicted that if these biotypes indeed corresponded to different cognitive and biological substrates, their adaptation to real life would be different. To this end, in the present work we have followed up the patients' population included in that work at 1st and 3rd years after the date of inclusion in the 2021 study and we report on the statistical comparisons of each clinical and real-life outcomes between them. The first cluster, with larger cognitive deficits and more severe biological alterations, showed during that period a decreased capacity for job tenure (1st and 3rd years), more admissions to a psychiatric ward (1st year) and a higher likelihood for quitting psychiatric follow-up (3rd year). Patients in the second cluster, with moderate cognitive deficits, were less compliant with prescribed treatment at the 3rd year. The differences in real-life outcomes may give additional external validity to that yielded by biological measurements to the described biotypes based on neurocognition.

Role of Radiotherapy and Hormone Therapy in Patients with Node-Positive Locally Advanced Prostate Cancer.

BACKGROUND: New-generation imaging techniques and the increasing use of surgery in high-risk prostate cancer (PCa) allow us to detect many cases of nodal disease at initial diagnosis or after resection. The treatment of PCa with pathologic regional nodes has evolved from the exclusive use of systemic therapy to its combination with locoregional treatment. It can also represent a benefit in the overall survival. However, the evidence from randomised studies is limited. Thus, we review the most relevant results in this scenario. MATERIALS AND METHODS: A literature search was conducted in MEDLINE, PubMed, EMBASE, Clinical-Trials.gov and Web of Science on January 2023 to review node-positive PCa by considering the relevant literature on this topic published with no restrictions on date and language. The search keywords used were "Prostatic Neoplasms" (MeSh) and "Node-positive" (Text Word) and "Radiotherapy" (MeSh) and ("Androgen Antagonists" (MeSh) or "Antineoplastic Agents, Hormonal" (MeSh)), which are indexed within the Medical Subject Headings database. RESULTS: The management of node-positive PCa has no clear definitive consensus at the initial disease diagnosis or after surgery. However, in this review, we summarise the existing literature for the management of these patients in both scenarios, considering imaging tests, radiotherapy, hormone therapy and second-generation hormonal treatments. CONCLUSIONS: The combination of radiotherapy and androgen-deprivation therapy is the treatment of choice. The addition of second-generation hormone therapy, plus the intensification of radiotherapy schedules, will likely change the treatment paradigm for these patients.

Interaction between chicken TRIM25 and MDA5 and their role in mediated antiviral activity against IBDV infection.

Infectious Bursal Disease Virus (IBDV) is the causative agent of an immunosuppressive disease that affects domestic chickens (Gallus gallus) severely affecting poultry industry worldwide. IBDV infection is characterized by a rapid depletion of the bursal B cell population by apoptosis and the atrophy of this chief lymphoid organ. Previous results from our laboratory have shown that exposure of infected cells to type I IFN leads to an exacerbated apoptosis, indicating an important role of IFN in IBDV pathogenesis. It has been described that recognition of the dsRNA IBDV genome by MDA5, the only known cytoplasmic pattern recognition receptor for viral RNA in chickens, leads to type I IFN production. Here, we confirm that TRIM25, an E3 ubiquitin ligase that leads to RIG-I activation in mammalian cells, significantly contributes to positively regulate MDA5-mediated activation of the IFN-inducing pathway in chicken DF-1 cells. Ectopic expression of chTRIM25 together with chMDA5 or a deletion mutant version exclusively harboring the CARD domains (chMDA5 2CARD) enhances IFN-ß and NF-ĸB promoter activation. Using co-immunoprecipitation assays, we show that chMDA5 interacts with chTRIM25 through the CARD domains. Moreover, chTRIM25 co-localizes with both chMDA5 and chMDA5 2CARD, but not with chMDA5 mutant proteins partially or totally lacking these domains. On the other hand, ablation of endogenous chTRIM25 expression reduces chMDA5-induced IFN-ß and NF-ĸB promoter activation. Interestingly, ectopic expression of either wild-type chTRIM25, or a mutant version (chTRIM25 C59S/C62S) lacking the E3 ubiquitin ligase activity, restores the co-stimulatory effect of chMDA5 in chTRIM25 knockout cells, suggesting that the E3-ubiquitin ligase activity of chTRIM25 is not required for its downstream IFN-ß and NF-ĸB activating function. Also, IBDV-induced expression of IFN-ß, Mx and OAS genes was reduced in chTRIM25 knockout as compared to wild-type cells, hence contributing to the enhancement of IBDV replication. Enhanced permissiveness to replication of other viruses, such as avian reovirus, Newcastle disease virus and vesicular stomatitis virus was also observed in chTRIM25 knockout cells. Additionally, chTRIM25 knockout also results in reduced MAVS-induced IFN-ß promoter stimulation. Nonetheless, similarly to its mammalian counterpart, chTRIM25 overexpression in wild-type DF-1 cells causes the degradation of ectopically expressed chMAVS.

Reproducibility of Neuroretinal Rim Measurements Obtained from High-Density Spectral Domain Optical Coherence Tomography Volume Scans.

Purpose: To compare the reproducibility of two-dimensional (2D) peripapillary retinal nerve fiber layer (RNFL) thickness and three-dimensional (3D) neuroretinal rim measurements using spectral domain optical coherence tomography (SDOCT) in normal and glaucoma subjects. Methods: One eye per subject for 27 normal and 40 glaucoma subjects underwent repeat SDOCT RNFL thickness scans and optic nerve volume scans on the same day. From the volume scan, custom software calculated five neuroretinal rim parameters: 3D minimum distance band (MDB) thickness, 3D MDB area, 3D rim volume, 2D rim area, and 2D rim thickness. Within-subject variance (Sw), coefficient of variation (CV), and intraclass correlation coefficient (ICC) were analyzed. Results: MDB thickness and RNFL thickness have similar reproducibility among normal and glaucoma subjects (eg, global MDB thickness CVs of 2.4% and 3.6%, and global RNFL thickness CVs of 1.3% and 2.2%; P > 0.05 for both comparisons). Reproducibility of MDB thickness was lower in glaucoma patients for the superior and inferior quadrants compared to normal subjects (CVs of 9.6% versus 3.4% and 6.9% versus 2.7%; P < 0.05, respectively). There were no statistically significant differences between both groups for RNFL thickness in the four quadrants. For both patient groups and for all regions, MDB thickness had the lowest CVs among all five neuroretinal rim parameters (eg, global MDB thickness CVs of 2.4% and 3.6% versus 3.0% and 18.9% for the other four neuroretinal rim parameters). Conclusion: Global MDB and global RNFL thickness are similarly reproducible among normal and glaucoma subjects, though MDB thickness for the superior and inferior quadrants is less reproducible among glaucoma subjects.

Two pediatric cases of reticular corneal epithelial edema associated with netarsudil.

Purpose: To report two pediatric cases of reticular corneal epithelial edema associated with the use of netarsudil ophthalmic solution 0.02%. Observations: In Case 1, a six-year-old male with glaucoma following cataract surgery was treated with netarsudil for thirteen months and developed diffuse reticular corneal epithelial edema on post-operative day one after undergoing transscleral diode cyclophotocoagulation for persistently elevated intraocular pressures. In Case 2, a three-month-old male with bilateral ocular hypertension developed unilateral inferior reticular corneal epithelial edema five weeks after initiation of netarsudil, which had been discontinued in the fellow eye two weeks prior. In both cases, the reticular epithelial edema resolved following cessation of netarsudil. Conclusions and Importance: Netarsudil-associated reticular corneal epithelial edema can occur in infants and young children.

Cognitive-Behavioral Therapy and Anxiety and Depression Level in Pediatric Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND: Although some meta-analyses have identified potential moderators associated with treatment outcomes for pediatric obsessive-compulsive disorder (OCD), there is as yet no consensus regarding the influence of anxiety and depression symptoms on the recovery from pediatric OCD. A meta-analysis was conducted to investigate the effects of depression and anxiety symptoms and their comorbidities on the efficacy of CBT in pediatric OCD, as well as other potential moderators that may be associated with outcomes. METHOD: An exhaustive literature search from 1983 to March 2021 located 22 published articles that applied cognitive-behavioral therapy (CBT) to pediatric OCD, producing a total of 26 treatment groups. Some of the moderator variables analyzed included age, gender, comorbidity baseline in anxiety, depression and obsession, and methodological quality. RESULTS: Results showed that the psychological treatment of OCD achieves clinically significant effectiveness, both for measures of obsessions and compulsions ( d + = 2.030), and for anxiety ( d + = 0.613) and depression ( d + = 0.451). An explanatory model for the CY-BOCS effect sizes showed that three moderator variables were statistically related: the mean of the CY-BOCS (Children´s Yale Brown Obsessive Compulsive Scale) in pretest, the effect size for anxiety, and the mean age of the sample. CONCLUSIONS: CBT reduced obsessive-compulsive symptoms and, to a lesser extent, anxiety and depression symptoms. Since anxiety symptoms are reduced with the same therapy, resources would be saved compared to other treatments.