Immunization of recombinant NS3 protein (protease region) of dengue virus induces high levels of CTLA-4 and apoptosis in splenocytes of BALB/c mice.

DENV infection outcomes depend on the host's variable expression of immune receptors and mediators, leading to either resolution or exacerbation. While the NS3 protein is known to induce robust immune responses, the specific impact of its protease region epitopes remains unclear. This study investigated the effect of recombinant NS3 protease region proteins from all four DENV serotypes on splenocyte activation in BALB/c mice (n = 5/group). Mice were immunized with each protein, and their splenocytes were subsequently stimulated with homologous antigens. We measured the expression of costimulatory molecules (CD28, CD80, CD86, CD152) by flow cytometry, along with IL-2 production, CD25 expression, and examined the antigen-specific activation of CD4 + and CD8 + T cells. Additionally, the expression of IL-1, IL-10, and TGF-ß1 in splenocytes from immunized animals was assessed. Apoptosis was evaluated using Annexin V/PI staining and DNA fragmentation analysis. Stimulation of splenocytes from immunized mice triggered apoptosis (phosphatidylserine exposure and caspase 3/7 activation) and increased costimulatory molecule expression, particularly CD152. Low IL-2 production and low CD25 expression, as well as sustained expression of the IL-10 gene. These results suggest that these molecules might be involved in mechanisms by which the NS3 protein contributes to viral persistence and disease pathogenesis.

Urofacial (Ochoa) syndrome with a founder pathogenic variant in the HPSE2 gene: a case report and mutation origin.

Urofacial syndrome or Ochoa syndrome (UFS or UFOS) is a rare disease characterized by inverted facial expression and bladder dysfunction that was described for the first time in Colombia. It is an autosomal recessive pathology with mutations in the HPSE2 and LRIG2 genes. However, 16% of patients do not have any mutations associated with the syndrome. Despite the importance of neurobiology in its pathophysiology, there are no neurological, neuropsychological, or psychological studies in these patients. A 30-year-old male from Medellín, Colombia, with a significant perinatal history, was diagnosed with grade 4 hydronephrosis on his first ultrasound test. At 4 months of age, symptoms such as hypomimia, lagophthalmos, and recurrent urinary tract infections started to manifest. Imaging studies revealed urinary tract dilatation, vesicoureteral reflux, and a double collector system on his left side, which led to the diagnosis of UFS. Multiple procedures, including vesicostomy, ureterostomy, and enterocystoplasty, were performed. At 20 years of age, he achieved urinary sphincter control. Genetic analysis revealed a founder pathogenic variant, c.1516C > T (p.Arg506Ter), in the HPSE2 gene, which produces a truncated protein that lacks 86 amino acids. This variant is classified as pathogenic according to the ClinVar database for UFS. The mutation age is approximately 260-360 years, and the two alleles share a 7.2-7.4 Mb IBD segment. Moreover, we detected European local ancestry in the IBD segment, which is consistent with a Spanish introduction. Neurological examination, neuropsychological assessment, and psychological testing revealed no abnormalities, except for high stress levels. Clinical analysis of this patient revealed distorted facial expression and detrusor-sphincter dyssynergia, which are typical of patients with UFS. Genetic analysis revealed a pathogenic variant in the HPSE2 gene of European origin and a mutation age of 260-360 years. From a neurological, neuropsychological, and psychological (emotional and personality) perspective, the patient showed no signs or symptoms of clinical interest.

Updating and profiling the natural product-likeness of Latin American compound libraries.

Compound databases of natural products play a crucial role in drug discovery and development projects and have implications in other areas, such as food chemical research, ecology and metabolomics. Recently, we put together the first version of the Latin American Natural Product database (LANaPDB) as a collective effort of researchers from six countries to ensemble a public and representative library of natural products in a geographical region with a large biodiversity. The present work aims to conduct a comparative and extensive profiling of the natural product-likeness of an updated version of LANaPDB and the individual ten compound databases that form part of LANaPDB. The natural product-likeness profile of the Latin American compound databases is contrasted with the profile of other major natural product databases in the public domain and a set of small-molecule drugs approved for clinical use. As part of the extensive characterization, we employed several chemoinformatics metrics of natural product likeness. The results of this study will capture the attention of the global community engaged in natural product databases, not only in Latin America but across the world.

Clinical Course and Outcomes of Autoimmune Versus Non-Autoimmune Surgically Induced Scleral Necrosis: A Multicentric Comparative Study.

BACKGROUND: To analyze the clinical course and outcomes of autoimmune vs. non-autoimmune surgically induced scleral necrosis (SISN). METHODS: Multicentric, retrospective, comparative cohort study. Eighty-two eyes of 70 patients with SISN were classified according to pathogenic mechanism into autoimmune vs. non-autoimmune. Main outcome measures included necrosis onset, type of surgery, associated systemic disease, visual acuity, and treatment were analysed in patients followed for ≥ 6 months. RESULTS: Forty-six (65.7%) patients were women, and the median age was 66 (range: 24-90) years. Most patients (82.9%) had unilateral disease. The median time between surgery and SISN onset was 58 (1-480) months. Thirty-one (37.8%) eyes were classified as autoimmune, and 51 (62.2%) as non-autoimmune SISN. Autoimmune SISN was associated with a shorter time between the surgical procedure and SISN onset than non-autoimmune cases (median of 26 vs. 60 months, p = 0.024). Also, autoimmune SISN was associated with cataract extraction (93.5% vs. 25.5%, p < 0.001), severe scleral inflammation (58.1% vs. 17.6%, p < 0.001), and higher incidence of ocular complications (67.7% vs. 33.3%, p = 0.002) than non-autoimmune cases. Remission was achieved with medical management alone in 44 (86.3%) eyes from the non-autoimmune and in 27 (87.1%) from the autoimmune group (p = 0.916). Surgical management was required in 11 (13.4%) eyes, including two requiring enucleations due to scleral perforation and phthisis bulbi. CONCLUSIONS: Eyes with autoimmune SISN had a higher rate of cataract surgery, severe scleral inflammation, and ocular complications. Early SISN diagnosis and appropriate management, based on clinical features and pathogenic mechanisms, are critical to avoid sight-threatening complications.

[Feeling analysis on allergen immunotherapy on Twitter using an unsupervised machine learning model]. / Análisis de sentimientos acerca de la inmunoterapia con alérgenos en Twitter mediante un modelo de aprendizaje automático no supervisado.

OBJECTIVE: Analyze feelings about allergen-specific immunotherapy on Twitter using the VADER model VADER (Valence Aware Dictionary and sEntiment Reasoner) model. METHODS: tweets related to specific allergen immunotherapy were obtained through the Twitter Application Programming Interface (API). The keywords "allergy shot" were used between January 1, 2012, and December 31, 2022. The data was processed by removing URLs, usernames, hashtags, multiple spaces, and duplicate tweets. Subsequently, a sentiment analysis was performed using the VADER model. RESULTS: A total of 34,711 tweets were retrieved, of which 1928 were eliminated. Of the remaining 32,783 tweets, 32.41% expressed a negative sentiment, 31.11% expressed a neutral sentiment, and 36.47% expressed a positive sentiment, with an average polarity of 0.02751 (neutral) over the 11-year period. CONCLUSIONS: The average polarity of tweets about allergen-specific immunotherapy is neutral over the 11 years analyzed. There was an annual increase in the average polarity over the years, with 2017, 2018, and 2022 having positive polarity averages. Additionally, the number of tweets decreased over time.

OBJETIVO: Analizar los sentimientos acerca de la inmunoterapia alérgeno-específica en Twitter mediante el modelo VADER (Valence Aware Dictionary and sEntiment Reasoner). MÉTODOS: Se utilizaron tweets relacionados con la inmunoterapia alérgeno-específica obtenidos a través del API (Application Programming Interface) de Twitter. Se incorporaron las palabras clave "allergy shot" en el período comprendido entre el 1 de enero de 2012 y el 31 de diciembre de 2022. Los datos obtenidos fueron procesados, eliminando las URL, nombres de usuarios, hashtags, espacios múltiples y tweets duplicados. Posteriormente, se realizó un análisis de sentimientos utilizando el modelo VADER. RESULTADOS: Se recolectaron 34,711 tweets, de los que se eliminaron 1928. De los 32,783 tweets restantes, se encontró que el 32.41% de los usuarios expresó un sentimiento negativo, el 31.11% un sentimiento neutral y el 36.47% un sentimiento positivo, con una media de polaridad de 0.02751 (neutral) a lo largo de los 11 años. CONCLUSIONES: La polaridad media de los tweets acerca de la inmunoterapia alérgeno-específica es neutral a lo largo de los 11 años analizados. Existe un aumento anual en la polaridad media positiva a lo largo de los años, sobre todo entre 2017, 2018 y 2022. La cantidad de tweets disminuyó con el tiempo.

Outcomes of accelerated corneal cross-linking for pediatric and adult keratoconus: a comparative study.

PURPOSE: To compare the visual, refractive, and topographic outcomes of a high irradiance accelerated corneal crosslinking (ACXL) protocol after a 12-month follow-up between pediatric and adult patients with progressive keratoconus (KC). METHODS: Retrospective, comparative, cohort study. Patients with KC were divided into two groups: pediatric (≤ 18 years) and adult (> 18 years). All of them were managed with epi-OFF ACXL (30 mW/cm2, 8 min, pulsed 1:1 on and off = 7.2 J/cm2). Visual, refractive, and topographic values were measured preoperatively and at 1, 3, 6, and 12 months postoperative. KC progression, defined as a Kmax increase of ≥ 1D during follow-up, was recorded. RESULTS: Eighty-nine eyes (53 patients) were included for analysis; 45 (50.6%) eyes were from pediatric patients and 44 (49.4%) from adults. At one-year follow-up, pediatric patients experienced significantly higher rates of progression (22.2% vs. 4.5%, p = .014). Contrariwise, female gender (Beta = - 3.62, p = .018), a baseline uncorrected visual acuity of Snellen ≥ 20/60 (Beta = - 5.96, p = .007), and being ≥ 15 years at ACXL treatment (Beta = - 0.31, p = .021) were associated with non-progressive disease. A significant improvement in best-corrected visual acuity, Kmin, Km, and Kmax was recorded in both groups. Overall, 86.5% of eyes from both groups showed Kmax stabilization or improvement. CONCLUSIONS: Despite the similarity in visual, refractive, and topographic outcomes in both groups, younger age was associated with KC progression after ACXL at one year of follow-up.

Risk factors contributing to infection with SARS-CoV-2 are modulated by sex.

Throughout the early stages of the COVID-19 pandemic in Mexico (August-December 2020), we closely followed a cohort of n = 100 healthcare workers. These workers were initially seronegative for Immunoglobulin G (IgG) antibodies against SARS-CoV-2, the virus that causes COVID-19, and maintained close contact with patients afflicted by the disease. We explored the database of demographic, physiological and laboratory parameters of the cohort recorded at baseline to identify potential risk factors for infection with SARS-CoV-2 at a follow-up evaluation six months later. Given that susceptibility to infection may be a systemic rather than a local property, we hypothesized that a multivariate statistical analysis, such as MANOVA, may be an appropriate statistical approach. Our results indicate that susceptibility to infection with SARS-CoV-2 is modulated by sex. For men, different physiological states appear to exist that predispose to or protect against infection, whereas for women, we did not find evidence for divergent physiological states. Intriguingly, male participants who remained uninfected throughout the six-month observation period, had values for mean arterial pressure and waist-to-hip ratio that exceeded the normative reference range. We hypothesize that certain risk factors that worsen the outcome of COVID-19 disease, such as being overweight or having high blood pressure, may instead offer some protection against infection with SARS-CoV-2.

Actinic conjunctivitis and its relationship with prurigo in an indigenous population from the Highlands of Chiapas, Mexico.

PURPOSE: Actinic conjunctivitis (AC), along with cheilitis (AChe), is part of the clinical spectrum of actinic prurigo (AP), a rare photo dermatosis that affects high-risk populations. We analyzed the clinical manifestations and onset of actinic conjunctivitis (AC), and its relationship with prurigo (AP) in a susceptible population. METHODS: This prospective observational cohort study was performed on Indigenous populations from the highlands of Chiapas, Mexico. Thorough dermatological and ophthalmological examinations were performed in patients attending a primary health care center. The clinical features, labor and environmental factors, onset timing, and clinical staging of AC and AP were analyzed. RESULTS: Of the 2913 patients studied, 54 patients (108 eyes) (1.8%) had AC, and 14 patients (25.9%) had AP. The mean age at diagnosis was 36.18 ± 18.52 years (6-70 years). The mean residential altitude was 1884 ± 434.2 m above sea level. Mean self-reported sun exposure was 5.14 ± 3.1 h a day (0.5-12 h). A total of 90.7% reported exposure to biomass fuels during cooking, and 50% to farm animals. AC was the sole manifestation in 70% of the cases. All patients had nasal and temporal photo-exposed conjunctiva. Among the eyes, 12.9% were classified as stage-1, 64.8% as stage-2, and 22.2% stage-3. A total of 83.3% of the patients had hyperpigmented lesions, and 35.1% had evaporative dry eye disease. CONCLUSIONS: AC may be the initial or sole manifestation of AP. Most AC cases (87%) were initially observed at the advanced stages of the disease. Although solar exposure was not associated with late AC stages, a positive association was found with farm animal exposure. Evaporative dry eye associated with meibomian gland dysfunction has not been previously reported in patients with AC.

The visual impact of higher-order aberrations in patients with pediatric blepharokeratoconjunctivitis.

PURPOSE: To analyze higher-order aberrations (HOAs) and their visual impact in a pediatric blepharokeratoconjunctivitis (PBKC) cohort compared with healthy controls. METHODS: Prospective case-control study of pediatric patients (≤ 16 years old). Subjects underwent wavefront aberrometry analysis to compare HOAs and their impact on visual quality. RESULTS: A total of 150 eyes from 76 patients were included in the analysis. The PBKC group consisted of 50 eyes and the control group of 100 healthy eyes. Mean age was 10.39 ± 3.81 years for the PBKC group and 10.80 ± 3.61 years for the controls. Mean corrected-distance visual acuity (CDVA) was 0.24 ± 0.21 logMAR in the PBKC group and 0.07 ± 0.1 in the controls (P < 0.001). Mean astigmatism was 1.6 ± 1.98D in the PBKC group vs. 0.67 ± 0.76D in the control group (P = 0.01). Mean RMS of HOAs was 1.05 ± 1.7mm in the PBKC group and 0.41 ± 0.18mm in the controls (P < 0.001). The mean modulation transfer function (MTF) in the PBKC group was significantly lower (16.37 ± 16.32) than controls (30.3 ± 23.57) (P < 0.001). Corneal leukomas, stromal vascularization, peripheral nummular subepithelial scars, and pannus formation are associated with increased HOAs. CONCLUSIONS: There was a significant increase in total HOAs of eyes with PBKC compared to healthy controls. Corneal opacity, vascularization, and scarring are associated with increased HOAs. The PBKC eye aberration profile: coma, secondary astigmatism, quadrafoil, and pentafoil, were associated with decreased CDVA and visual quality (PSF and MTF).

RNA-seq analysis reveals modulation of inflammatory pathways by an enriched-triterpene natural extract in mouse and human macrophage cell lines.

Chronic inflammation is crucial in developing insulin resistance and type 2 diabetes. Previous studies have shown that a leaf extract of Eucalyptus tereticornis, with ursolic acid (UA), oleanolic acid (OA), and ursolic acid lactone (UAL) as the main molecules (78 %) mixed with unknown minor metabolites (22 %), provided superior anti-inflammatory, hypoglycemic, and hypolipidemic effects than reconstituted triterpenoid mixtures in macrophage cell lines and a pre-diabetic mouse model. Further identification of the molecular mechanisms of action of this mixture of triterpenes is required. This study aims to analyse the RNA expression profiles of mouse and human macrophage cell lines treated with the natural extract and its components. Activated macrophage cell lines were treated with the natural extract, UA, OA, UAL or a triterpene mixture (M1). RNA was extracted and sequenced using the DNBseq platform and the EnrichR software to perform gene enrichment analysis using the Gene Ontology database, Kyoto Encyclopedia of Genes and Genomes, and Reactome. To conduct clustering analysis, we standardised the normalised counts of each gene and applied k-means clustering. The combination of molecules in the natural extract has an additive or synergic effect that affects the expression of up-regulated genes by macrophage activation. Triterpenes (M1) regulated 76 % of human and 68 % of mouse genes, while uncharacterised minority molecules could regulate 24 % of human and 32 % of mouse genes. The extract inhibited the expression of many cytokines (IL6, IL1, OSM), chemokines (CXCL3), inflammatory mediators (MMP8 and MMP13) and the JAK-STAT signalling pathway in both models. The natural extract has a more powerful immunomodulatory effect than the triterpene mixture, increasing the number of genes regulated in mouse and human models. Our study shows that Eucalyptus tereticornis extract is a promising option for breaking the link between inflammation and insulin resistance.

Genes and Pathways Involved in the Progression of Malignant Pleural Mesothelioma: A Meta-analysis of Genome-Wide Expression Studies.

Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural tissue that lines the lungs and is mainly associated with long latency from asbestos exposure. This tumor has no effective therapeutic opportunities nowadays and has a very low five-year survival rate. In this sense, identifying molecular events that trigger the development and progression of this tumor is highly important to establish new and potentially effective treatments. We conducted a meta-analysis of genome-wide expression studies publicly available at the Gene Expression Omnibus (GEO) and ArrayExpress databases. The differentially expressed genes (DEGs) were identified, and we performed functional enrichment analysis and protein-protein interaction networks (PPINs) to gain insight into the biological mechanisms underlying these genes. Additionally, we constructed survival prediction models for selected DEGs and predicted the minimum drug inhibition concentration of anticancer drugs for MPM. In total, 115 MPM tumor transcriptomes and 26 pleural tissue controls were analyzed. We identified 1046 upregulated DEGs in the MPM samples. Cellular signaling categories in tumor samples were associated with the TNF, PI3K-Akt, and AMPK pathways. The inflammatory response, regulation of cell migration, and regulation of angiogenesis were overrepresented biological processes. Expression of SOX17 and TACC1 were associated with reduced survival rates. This meta-analysis identified a list of DEGs in MPM tumors, cancer-related signaling pathways, and biological processes that were overrepresented in MPM samples. Some therapeutic targets to treat MPM are suggested, and the prognostic potential of key genes is shown.

Definition and Diagnostic Criteria for Pediatric Blepharokeratoconjunctivitis.

Importance: Pediatric blepharokeratoconjunctivitis (PBKC) is a chronic, sight-threatening inflammatory ocular surface disease. Due to the lack of unified terminology and diagnostic criteria, nonspecific symptoms and signs, and the challenge of differentiation from similar ocular surface disorders, PBKC may be frequently unrecognized or diagnosed late. Objective: To establish a consensus on the nomenclature, definition, and diagnostic criteria of PBKC. Design, Setting, and Participants: This quality improvement study used expert panel and agreement applying the non-RAND modified Delphi method and open discussions to identify unified nomenclature, definition, and definitive diagnostic criteria for PBKC. The study was conducted between September 1, 2021, and August 14, 2022. Consensus activities were carried out through electronic surveys via email and online virtual meetings. Results: Of 16 expert international panelists (pediatric ophthalmologists or cornea and external diseases specialists) chosen by specific inclusion criteria, including their contribution to scientific leadership and research in PBKC, 14 (87.5%) participated in the consensus. The name proposed was "pediatric blepharokeratoconjunctivitis," and the agreed-on definition was "Pediatric blepharokeratoconjunctivitis is a frequently underdiagnosed, sight-threatening, chronic, and recurrent inflammatory eyelid margin disease associated with ocular surface involvement affecting children and adolescents. Its clinical spectrum includes chronic blepharitis, meibomitis, conjunctivitis, and corneal involvement ranging from superficial punctate keratitis to corneal infiltrates with vascularization and scarring." The diagnostic criteria included 1 or more suggestive symptoms accompanied by clinical signs from 3 anatomical regions: the eyelid margin, conjunctiva, and cornea. For PBKC suspect, the same criteria were included except for corneal involvement. Conclusions and Relevance: The agreements on the name, definition, and proposed diagnostic criteria of PBKC may help ophthalmologists avoid diagnostic confusion and recognize the disease early to establish adequate therapy and avoid sight-threatening complications. The diagnostic criteria rely on published evidence, analysis of simulated clinical cases, and the expert panel's clinical experience, requiring further validation with real patient data analysis.

Conducta suicida en México: análisis comparativo entre población adolescente y adulta.

OBJETIVO: Estimar la prevalencia nacional de conductas suicidas en población adolescente y adulta, por características sociodemográficas, con los datos de la Encuesta Nacional de Salud y Nutrición (Ensanut 2022). Material y métodos. A partir de la Ensanut 2022 se analizan preguntas similares en adolescentes y adultos relacionadas con pensamiento e intento de suicidio alguna vez en la vida y en los últimos 12 meses. RESULTADOS: El 7.6% de la población adolescente y 7.7% de la población adulta pensó alguna vez en suicidarse. La prevalencia de intento de suicidio alguna vez en la vida fue de 6.5% en adolescentes y 3.5% en adultos, y 3.1% en adolescentes y 0.6% en adultos para los últimos 12 meses. Las mujeres reportaron la mayor prevalencia en comparación con los hombres, tanto en pensamiento como en intentos de suicidio. Conclusión. Los hallazgos refuerzan la importancia de establecer la prevención del suicidio en jóvenes como una prioridad en la agenda nacional de salud.

Reaching "covidianidad": A qualitative study of the impact of the COVID-19 pandemic on the perceived mental health of health care workers in the Dominican Republic.

We aimed to explore how the COVID-19 pandemic affected the lives of healthcare workers (HCWs) in the Dominican Republic. We also aimed to identify the types of resources that HCWs felt were needed to support their mental health. We used purposive and convenience sampling in four health centers in the eastern Dominican Republic to recruit 28 HCWs (doctors, nurses, psychologists, and community health workers) between April 2021 and August 2021. Through semi-structured interviews, we elicited HCWs experiences during the pandemic and how they felt these experiences impacted their mental health. Interview transcripts were analyzed using an inductive/deductive thematic approach. Main stressors experienced during the pandemic by HCWs and their sequelae included anxiety due to misinformation and uncertainty, fear of the disease, the robustness of pandemic-related changes they faced in their work and daily life, and COVID-19's economic impact. HCWs reflected on protective factors that transformed their acute sense of crisis felt at the beginning of the pandemic into what HCWs referred to as "covidianidad [everyday COVID]", a situation that became manageable through mechanisms including social support, professional motivation, positive work environment and resilience. Lastly, HCWs identified stigmatization of and limited access to mental health services as challenges to supporting their mental health. While Dominican HCWs were vulnerable to the challenges posed by COVID-19 in sustaining their mental health, for many, the situation became manageable through the evolution of "covidianidad." Further research and interventions are needed to reduce stigmatization of mental health services and foment a positive environment for HCWs' mental health, to promote resiliency to future challenges.

NR3C1 and NR3C2 Genes Increase the Risk of Suicide Attempt in Psychiatric Disorder Patients with History of Childhood Trauma.

Background: Hypothalamic-pituitary-adrenal axis gene variants and childhood trauma (CT) are considered risk factors for suicide attempt (SA). The aim of the present study was analyzed gene x environment (GxE) interaction of NR3C1, NR3C2, and CT, and NR3C1 and NR3C2 gene expression in the development of SA with CT. Participants and Methods: A total of 516 psychiatric Mexican patients from Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz. Among them, 274 had SA at least once and 242 had not SA. Genetic variants of NR3C1 and NR3C2 were genotyped in all the patients, of which were obtained the CT information from medical records. Additionally, the gene expression of NR3C1 and NR3C2 was also analyzed for a subsample of 96 patients, obtaining the TC information from Childhood Trauma Questionnaire (CTQ). Results: The analysis showed a GxE interaction of NR3C1, NR3C2, and CT (OR=2.8, 95% CI [1.9-3.9], p<0.0001). Interactions were also observed with neglect (OR=2.1, 95% CI [1.4-3.1], p<0.0001), emotional abuse (OR=2.1, 95% CI [1.5-3], p<0.0001), and sexual abuse (OR=2.4, 95% CI [1.4-2.9], p<0.0001) in the prediction of SA. The analysis of gene expression identified an overexpression of NR3C1 in SA patients with high scores for physical and sexual abuse (p<0.0001; p<0.0006, respectively) and emotional neglect (p=0.014). An underexpression was observed of NR3C2, associated with high scores of trauma subtypes (p<0.0001) except physical neglect. Additionally, we observed an overexpression of NR3C1 gene in patients with SA carriers of A allele of rs6191 (p=0.0015). Also, overexpression of NR3C1 gene in carriers of G allele of rs6198 and underexpression of NR3C2 gene in carriers of G allele of rs5522 (p<0.0001). Conclusion: Our findings suggest that genetic variants of NR3C1 and NR3C2 differentially affect expression levels, increasing the susceptibility to SA in psychiatric patients with a history of CT.

Navigating the Chemical Space and Chemical Multiverse of a Unified Latin American Natural Product Database: LANaPDB.

The number of databases of natural products (NPs) has increased substantially. Latin America is extraordinarily rich in biodiversity, enabling the identification of novel NPs, which has encouraged both the development of databases and the implementation of those that are being created or are under development. In a collective effort from several Latin American countries, herein we introduce the first version of the Latin American Natural Products Database (LANaPDB), a public compound collection that gathers the chemical information of NPs contained in diverse databases from this geographical region. The current version of LANaPDB unifies the information from six countries and contains 12,959 chemical structures. The structural classification showed that the most abundant compounds are the terpenoids (63.2%), phenylpropanoids (18%) and alkaloids (11.8%). From the analysis of the distribution of properties of pharmaceutical interest, it was observed that many LANaPDB compounds satisfy some drug-like rules of thumb for physicochemical properties. The concept of the chemical multiverse was employed to generate multiple chemical spaces from two different fingerprints and two dimensionality reduction techniques. Comparing LANaPDB with FDA-approved drugs and the major open-access repository of NPs, COCONUT, it was concluded that the chemical space covered by LANaPDB completely overlaps with COCONUT and, in some regions, with FDA-approved drugs. LANaPDB will be updated, adding more compounds from each database, plus the addition of databases from other Latin American countries.

Challenges in the diagnosis and management of simultaneous, bilateral, toxic anterior segment syndrome after phacorefractive surgery.

A 59-year-old woman presented with a 24-hour history of severe, bilateral, painless vision loss starting 1 day after immediately sequential, bilateral, phacorefractive surgery with multifocal intraocular lens (IOL) implantation at another institution. Best-corrected visual acuity was counting fingers at 1 foot in the right eye and 20/100 in the left eye. Slit-lamp evaluation showed a dense fibrin membrane on the anterior surface of the IOL and significant anterior chamber inflammation in both eyes. B-scan ultrasound revealed bilateral vitreous haze, without membrane formation. The rapid onset, absence of sharp pain, ciliary injection, conjunctival chemosis, eyelid edema, and erythema raised suspicion for bilateral toxic anterior segment syndrome. Significant clinical improvement after high-dose prednisone and hourly prednisolone acetate eye drops supported the diagnosis. After 6 months of tapering anti-inflammatory therapy, optical coherence tomography of the macula showed no pathologic changes, and the patient's best-corrected visual acuity improved to 20/25 in both eyes.

Validation of an Ultraviolet Light Response Gene Signature for Predicting Prognosis in Patients with Uveal Melanoma.

Uveal melanoma (UVM) is a highly aggressive ocular cancer with limited therapeutic options and poor prognosis particularly for patients with liver metastasis. As such, the identification of new prognostic biomarkers is critical for developing effective treatment strategies. In this study, we aimed to investigate the potential of an ultraviolet light response gene signature to predict the prognosis of UVM patients. Our approach involved the development of a prognostic model based on genes associated with the cellular response to UV light. By employing this model, we generated risk scores to stratify patients into high- and low-risk groups. Furthermore, we conducted differential expression analysis between these two groups and explored the estimation of immune infiltration. To validate our findings, we applied our methodology to an independent UVM cohort. Through our study, we introduced a novel survival prediction tool and shed light on the underlying cellular processes within UVM tumors, emphasizing the involvement of immune subsets in tumor progression.

Limited granulomatosis with polyangiitis in children with idiopathic orbital inflammation: a case series and literature review.

Idiopathic orbital inflammation (IOI) is a diagnosis of exclusion, but the exclusion of other inflammatory diseases of the orbit is broad and relies on clinician experience, response to corticosteroid, or biopsy. This study aimed to investigate the presence of granulomatosis with polyangiitis (GPA) in patients initially diagnosed as IOI and describe its clinicopathological features, ANCA status, treatment, and outcome. We performed a retrospective case series study of children diagnosed with limited GPA (L-GPA) in patients with IOI. A systematic review of the literature was performed in children with GPA and orbital mass. Eleven of 13 (85%) patients with IOI had L-GPA. Two additional patients with orbital mass and L-GPA were included in this analysis. The median age was 10 years, and 75% were female. Twelve cases were ANCA positive and 77% were MPO-pANCA positive. Most patients had a poor response to treatment and had a high relapse rate. Based on literature review, 28 cases were found. Most (78.6%) were female with a median age of 9 years. Three patients were misdiagnosed as IOI. Patients with L-GPA more frequently had MPO-pANCA positivity (35%) than children with systemic GPA (18%) and were less often PR3-cANCA positive than patients with systemic GPA (18% vs. 46%). L-GPA accounts for a high prevalence of children diagnosed as IOI. The high prevalence of MPO-pANCA observed in our study may be related to L-GPA rather than with the orbital mass. Long-term follow-up, orbital biopsy, and serial ANCA testing are necessary to exclude GPA in patients with IOI.