Key Clinical and Histopathological Features of a Pterygium-Like Induced Lesion in a Rabbit Model.

Purpose: Surgery is the definitive treatment for pterygium; therefore, reliable animal models are required for translational research. The goal of this investigation was to establish a standardized preclinical model of pterygium-like lesion. Methods: A subconjunctival injection of fibroblasts (NIH3T3) and extracellular matrix was administered to 22 New Zealand rabbits. Clinical evaluation was assessed at different points, the severity of the lesion was scored according to four grades and correlated with the area of hyperemia and the histopathological findings on day 23. Results: Thirteen of 22 eyes (60%) developed pterygium-like lesions after 7 days and progressed through different grades. Initially, grade 3, characterized by an elevated and fleshiness conjunctiva with tortuous hyperemia, was evident on day 7. By day 15, lesion decreased to grade 2, with less elevation and hyperemia. Subsequent improvement was noted, with grade 1 on day 18. Finally, day 23 was marked by a white‒yellow lesion, classified as grade 4. The area of hyperemia increased from grade 2 to grade 3 (P < 0.05) and decreased from grade 3 to grade 4 (P ≤ 0.05). Histopathological analysis revealed a tendency toward increasing inflammation at grades 2, 3, and 4. There was a correlation between clinical features and the degree of inflammation. Conclusions: Subconjunctival injection of NIH3T3 and extracellular matrix induces a pterygium-like lesion that progresses across four grades, beginning with an acute inflammatory process that evolve a chronic form. This study provides a replicable model for simulating pterygium. Translational Relevance: The development of a standardized preclinical model of pterygium to evaluate new pharmacological or surgical treatments.

A congenital periocular leiomyosarcoma in a dairy calf.

A mass was removed surgically from the right orbit of a 1-d-old Holstein calf. Grossly, the mass filled the rostral part of an enlarged orbit and compressed the globe toward the caudal pole of the orbit. The brown, 6-cm tumor had central yellow and brown areas, and a smooth, glistening cut surface. Microscopically, the neoplasm was highly cellular and composed of spindle cells arranged in irregular, broad, interlacing streams and bundles, forming a herringbone pattern and supported by a sparse collagenous matrix. Neoplastic cells infiltrated surrounding soft tissues and compressed the globe. The neoplastic cells had positive immunolabeling for α-smooth muscle actin, desmin, and vimentin, and negative immunolabeling for factor VIII, myoglobin, cytokeratin, and skeletal muscle actin. Histopathology and immunohistochemistry results confirmed a diagnosis of leiomyosarcoma. To our knowledge, congenital periocular leiomyosarcoma has not been reported in cattle previously. This rare tumor could be included as a differential diagnosis in newborn calves with periocular masses.

Intestinal pathology in goats challenged with Clostridium perfringens type D strain CN1020 wild-type and its genetically modified derivatives.

Clostridium perfringens type D is the causative agent of enterotoxemia in sheep, goats, and cattle. Although in sheep and cattle, the disease is mainly characterized by neurological clinical signs and lesions, goats with type D enterotoxemia frequently have alterations of the alimentary system. Epsilon toxin (ETX) is the main virulence factor of C. perfringens type D, although the role of ETX in intestinal lesions in goats with type D enterotoxemia has not been fully characterized. We evaluated the contribution of ETX to C. perfringens type D enteric pathogenicity using an intraduodenal challenge model in young goats, with the virulent C. perfringens type D wild-type strain CN1020; its isogenic etx null mutant; an etx-complemented strain; and sterile, non-toxic culture medium. The intestinal tract of each animal was evaluated grossly, microscopically, and immunohistochemically for activated caspase-3. Both ETX-producing strains induced extensive enterocolitis characterized by severe mucosal necrosis, apoptosis, and diffuse suppurative infiltrates. No significant gross or microscopic lesions were observed in goats inoculated with the non-ETX-containing inocula. These results confirm that ETX is essential for the production of intestinal lesions in goats with type D disease. Also, our results suggest that the intestinal pathology of type D enterotoxemia in goats is, at least in part, associated with apoptosis.

Outbreak of Chlamydia psittaci Infection in a Commercial Psittacine Breeding Aviary in Argentina.

Chlamydiosis, caused by Chlamydia psittaci is a bacterial infection found in at least 465 species of birds worldwide. It is highly contagious among birds and can spread to humans. In birds, the disease can manifest itself in acute, subacute, and chronic forms with signs including anorexia, diarrhea, lethargy, weight loss, or, occasionally, mucopurulent or serous oculonasal discharge. This article describes an outbreak of chlamydiosis that occurred in a commercial psittacine breeding aviary in 2021 in Buenos Aires province, Argentina. In total, 16 juvenile blue-fronted parrots, more than 60 blue-fronted parrot chicks, and 2 adult macaws died during the outbreak. In all cases, clinical signs were weight loss, diarrhea, yellowish green excrement, and respiratory distress. The necropsy of four juvenile blue-fronted parrots, two blue-fronted parrot chicks, and two adult macaws revealed cachexia, hepatomegaly, splenomegaly, splenic petechial hemorrhages, ascites, pulmonary edema, and hydropericardium. Histologically, multifocal lymphoplasmacytic and heterophilic airsaculitis, multifocal lymphoplasmacytic and necrotizing hepatitis with intracytoplasmic elementary bodies, multifocal necro-heterophilic hepatitis, multifocal lymphoplasmacytic nephritis, and diffuse heterophilic pneumonia were found. A presumptive diagnosis was established based on gross and microscopic lesions, and it was confirmed using immunohistochemistry and polymerase chain reactions. The sequencing and phylogenetic analysis of the ompA gene revealed genotype A and B of Chlamydia psittaci.

Expression patterns of Mal genes and association with differential maltose and maltotriose transport rate of two Saccharomyces pastorianus yeasts.

Beer brewing is a well-known process that still faces great challenges, such as the total consumption of sugars present in the fermentation media. Lager-style beer, a major worldwide beer type, is elaborated by Saccharomyces pastorianus (Sp) yeast, which must ferment high maltotriose content worts, but its consumption represents a notable problem, especially among Sp strains belonging to group I. Factors, such as fermentation conditions, presence of maltotriose transporters, transporter copy number variation, and genetic regulation variations contribute to this issue. We assess the factors affecting fermentation in two Sp yeast strains: SpIB1, with limited maltotriose uptake, and SpIB2, known for efficient maltotriose transport. Here, SpIB2 transported significantly more maltose (28%) and maltotriose (32%) compared with SpIB1. Furthermore, SpIB2 expressed all MAL transporters (ScMALx1, SeMALx1, ScAGT1, SeAGT1, MTT1, and MPHx) on the first day of fermentation, whereas SpIB1 only exhibited ScMalx1, ScAGT1, and MPH2/3 genes. Some SpIB2 transporters had polymorphic transmembrane domains (TMD) resembling MTT1, accompanied by higher expression of these transporters and its positive regulator genes, such as MAL63. These findings suggest that, in addition to the factors mentioned above, positive regulators of Mal transporters contribute significantly to phenotypic diversity in maltose and maltotriose consumption among the studied lager yeast strains.IMPORTANCEBeer, the third most popular beverage globally with a 90% market share in the alcoholic beverage industry, relies on Saccharomyces pastorianus (Sp) strains for lager beer production. These strains exhibit phenotypic diversity in maltotriose consumption, a crucial process for the acceptable organoleptic profile in lager beer. This diversity ranges from Sp group II strains with a notable maltotriose-consuming ability to Sp group I strains with limited capacity. Our study highlights that differential gene expression of maltose and maltotriose transporters and its upstream trans-elements, such as MAL gene-positive regulators, adds complexity to this variation. This insight can contribute to a more comprehensive analysis needed to the development of controlled and efficient biotechnological processes in the beer brewing industry.

The Accuracy of the Learning-Curve Cumulative Sum Method in Assessing Brachial Plexus Block Competency.

BACKGROUND: The learning-curve cumulative sum method (LC-CUSUM) and its risk-adjusted form (RA-LC-CUSUM) have been proposed as performance-monitoring methods to assess competency during the learning phase of procedural skills. However, scarce data exist about the method's accuracy. This study aimed to compare the accuracy of LC-CUSUM forms using historical data consisting of sequences of successes and failures in brachial plexus blocks (BPBs) performed by anesthesia residents. METHODS: Using historical data from 1713 BPB performed by 32 anesthesia residents, individual learning curves were constructed using the LC-CUSUM and RA-LC-CUSUM methods. A multilevel logistic regression model predicted the procedure-specific risk of failure incorporated in the RA-LC-CUSUM calculations. Competency was defined as a maximum 15% cumulative failure rate and was used as the reference for determining the accuracy of both methods. RESULTS: According to the LC-CUSUM method, 22 residents (84.61%) attained competency after a median of 18.5 blocks (interquartile range [IQR], 14-23), while the RA-LC-CUSUM assigned competency to 20 residents (76.92%) after a median of 17.5 blocks (IQR, 14-25, P = .001). The median failure rate at reaching competency was 6.5% (4%-9.75%) under the LC-CUSUM and 6.5% (4%-9%) for the RA-LC-CUSUM method ( P = .37). The sensitivity of the LC-CUSUM (85%; 95% confidence interval [CI], 71%-98%) was similar to the RA-LC-CUSUM method (77%; 95% CI, 61%-93%; P = .15). Identical specificity values were found for both methods (67%; 95% CI, 29%-100%, P = 1). CONCLUSIONS: The LC-CUSUM and RA-LC-CUSUM methods were associated with substantial false-positive and false-negative rates. Also, small lower limits for the 95% CIs around the accuracy measures were observed, indicating that the methods may be inaccurate for high-stakes decisions about resident competency at BPBs.

Development and standardization of an enzyme-linked inmunosorbent for the detection of orthohantavirus infection in Argentina based on its bacterial-expressed nucleocapside protein.

We conducted a development and standardization of an IgG ELISA assay for serological detection of human orthohantavirus infections using the recombinant antigen rLECH13 produced in bacterial and derived from the LECHV. The evaluation and standardization were carried out by analyzing serum samples from a total of 50 patients with confirmed Hantavirus Pulmonary Syndrome (HPS) diagnosis through the reference technique, 50 negative sera, and 53 patients with other medical conditions. The data from the assay analysis showed a diagnostic sensitivity value of 95% and a diagnostic specificity of 80%. The high sensitivity of this novel assay leads us to conclude that rLECH13 is a feasible option for use in the immunodiagnostic of orthohantavirus infection. Additionally, it is crucial to have an antigen that can be produced under conditions that do not require highly complex laboratories. Furthermore, the new assay is cost-effective, reproducible, and demonstrates excellent performance.

Modeling of host PDZ-dependent interactions with SARS-CoV-2 envelope protein and changes in PDZ protein expression in macrophages and dendritic cells.

PDZ (PSD-95 [postsynaptic density protein 95]/Dlg [Discs large]/ZO-1 [zonula occludens-1]) domain-containing proteins constitute a large family of scaffolds involved in a wide range of cellular tasks and are mainly studied in polarity functions. Diverse host PDZ proteins can be targeted by viral pathogens that express proteins containing PDZ-binding motifs (PDZbms). Previously, we have identified host PDZ-based interactions with the SARS-CoV-2 E protein (2E) in human monocytes. Here, we deepen the study of these interactions by docking and molecular dynamics analyses to identify the most favorable PDZ-PDZbm interaction of 7 host PDZ proteins with the PDZbm of 2E. In addition, we analyzed changes in the expression of 3 of the PDZ proteins identified as 2E interactors in monocytes (syntenin, ZO-2, and interleukin-16), in human monocyte-derived macrophages and in dendritic cells upon stimulation. Our results suggest that these PDZ proteins may have important functions in professional antigen-presenting cells, and their targeting by the PDZbm of 2E, a central virulence determinant of SARS-CoV-2, supports the hypothesis that such PDZ-dependent interaction in immune cells may constitute a viral evasion mechanism. An inhibitor design based on the PDZbm of 2E in the development of drugs against a variety of diseases is discussed.

Chamaecyparis lawsoniana and Its Active Compound Quercetin as Ca2+ Inhibitors in the Contraction of Airway Smooth Muscle.

The Cupressaceae family includes species considered to be medicinal. Their essential oil is used for headaches, colds, cough, and bronchitis. Cedar trees like Chamaecyparis lawsoniana (C. lawsoniana) are commonly found in urban areas. We investigated whether C. lawsoniana exerts some of its effects by modifying airway smooth muscle (ASM) contractility. The leaves of C. lawsoniana (363 g) were pulverized mechanically, and extracts were obtained by successive maceration 1:10 (w:w) with methanol/CHCl3. Guinea pig tracheal rings were contracted with KCl, tetraethylammonium (TEA), histamine (HIS), or carbachol (Cch) in organ baths. In the Cch experiments, tissues were pre-incubated with D-600, an antagonist of L-type voltage-dependent Ca2+ channels (L-VDCC) before the addition of C. lawsoniana. Interestingly, at different concentrations, C. lawsoniana diminished the tracheal contractions induced by KCl, TEA, HIS, and Cch. In ASM cells, C. lawsoniana significantly diminished L-type Ca2+ currents. ASM cells stimulated with Cch produced a transient Ca2+ peak followed by a sustained plateau maintained by L-VDCC and store-operated Ca2+ channels (SOCC). C. lawsoniana almost abolished this last response. These results show that C. lawsoniana, and its active metabolite quercetin, relax the ASM by inhibiting the L-VDCC and SOCC; further studies must be performed to obtain the complete set of metabolites of the extract and study at length their pharmacological properties.

Testosterone Enhances KV Currents and Airway Smooth Muscle Relaxation Induced by ATP and UTP through P2Y4 Receptors and Adenylyl Cyclase Pathway.

Numerous studies suggest the involvement of adenosine-5'-triphosphate (ATP) and similar nucleotides in the pathophysiology of asthma. Androgens, such as testosterone (TES), are proposed to alleviate asthma symptoms in young men. ATP and uridine-5'-triphosphate (UTP) relax the airway smooth muscle (ASM) via purinergic P2Y2 and P2Y4 receptors and K+ channel opening. We previously demonstrated that TES increased the expression of voltage-dependent K+ (KV) channels in ASM. This study investigates how TES may potentiate ASM relaxation induced by ATP and UTP. Tracheal tissues treated with or without TES (control group) from young male guinea pigs were used. In organ baths, tracheas exposed to TES (40 nM for 48 h) showed enhanced ATP- and UTP-evoked relaxation. Tetraethylammonium, a K+ channel blocker, annulled this effect. Patch-clamp experiments in tracheal myocytes showed that TES also increased ATP- and UTP-induced K+ currents, and this effect was abolished with flutamide (an androgen receptor antagonist). KV channels were involved in this phenomenon, which was demonstrated by inhibition with 4-aminopyridine. RB2 (an antagonist of almost all P2Y receptors except for P2Y2), as well as N-ethylmaleimide and SQ 22,536 (inhibitors of G proteins and adenylyl cyclase, respectively), attenuated the enhancement of the K+ currents induced by TES. Immunofluorescence and immunohistochemistry studies revealed that TES did not modify the expression of P2Y4 receptors or COX-1 and COX-2, while we have demonstrated that this androgen augmented the expression of KV1.2 and KV1.5 channels in ASM. Thus, TES leads to the upregulation of P2Y4 signaling and KV channels in guinea pig ASM, enhancing ATP and UTP relaxation responses, which likely limits the severity of bronchospasm in young males.

Tracing the evolution of the chikungunya virus in Argentina, 2016-2023: independent introductions and prominence of Latin American lineages.

Chikungunya virus (CHIKV) has emerged as a significant public health concern due to its rapid spread and potential for causing debilitating epidemics. In Argentina, the virus has garnered attention since its introduction to the Americas in 2013, due to its growing incidence and impact in neighbouring countries. Here we present a comprehensive analysis of the spatiotemporal dynamics of CHIKV in Argentina, focusing on the evolutionary trajectory of its genetic variants. Through a combination of active surveillance, screening of historical and recent samples, and whole-genome sequencing, we traced the evolutionary history of CHIKV lineages circulating within the country. Our results reveal that two distinct genotypes circulated in Argentina: The Asian lineage during the 2016 epidemic and the ECSA lineage in 2023. This distribution reflects the dominance of particular variants across Latin America. Since 2023, the ECSA lineage has led to a surge in cases throughout the Americas, marking a significant shift. The replacement of lineages in the American region constitutes a major epidemiological event, potentially affecting the dynamics of virus transmission and the clinical outcomes in impacted populations. The spatiotemporal analysis highlights CHIKV's distribution across Argentina and underscores the significant role of human mobility, especially when considering recent epidemics in neighbouring countries such as Paraguay and Uruguay, which have facilitated the spread and introduction of the viral strain into different districts. By integrating epidemiological data with genomic insights, we elucidate the patterns of virus dissemination, highlighting key areas of transmission and potential factors contributing to its spread.

Lippia graveolens Essential Oil to Enhance the Effect of Imipenem against Axenic and Co-Cultures of Pseudomonas aeruginosa and Acinetobacter baumannii.

This research focuses on assessing the synergistic effects of Mexican oregano (Lippia graveolens) essential oil or carvacrol when combined with the antibiotic imipenem, aiming to reduce the pathogenic viability and virulence of Acinetobacter baumannii and Pseudomonas aeruginosa. The study highlighted the synergistic effect of combining L. graveolens essential oil or carvacrol with imipenem, significantly reducing the required doses for inhibiting bacterial growth. The combination treatments drastically lowered the necessary imipenem doses, highlighting a potent enhancement in efficacy against A. baumannii and P. aeruginosa. For example, the minimum inhibitory concentrations (MIC) for the essential oil/imipenem combinations were notably low, at 0.03/0.000023 mg/mL for A. baumannii and 0.0073/0.000023 mg/mL for P. aeruginosa. Similarly, the combinations significantly inhibited biofilm formation at lower concentrations than when the components were used individually, demonstrating the strategic advantage of this approach in combating antibiotic resistance. For OXA-51, imipenem showed a relatively stable interaction during 30 ns of dynamic simulation of their interaction, indicating changes (<2 nm) in ligand positioning during this period. Carvacrol exhibited similar fluctuations to imipenem, suggesting its potential inhibition efficacy, while thymol showed significant variability, particularly at >10 ns, suggesting potential instability. With IMP-1, imipenem also displayed very stable interactions during 38 ns and demonstrated notable movement and positioning changes within the active site, indicating a more dynamic interaction. In contrast, carvacrol and thymol maintained their position within the active site only ~20 and ~15 ns, respectively. These results highlight the effectiveness of combining L. graveolens essential oil and carvacrol with imipenem in tackling the difficult-to-treat pathogens A. baumannii and P. aeruginosa.

Novel Oliveros-like Clade C Mammarenaviruses from Rodents in Argentina, 1990-2020.

Following an Argentine Hemorrhagic Fever (AHF) outbreak in the early 1990s, a rodent survey for Junín virus, a New World Clade B arenavirus, in endemic areas of Argentina was conducted. Since 1990, INEVH has been developing eco-epidemiological surveillance of rodents, inside and outside the Argentine Hemorrhagic Fever endemic area. Samples from rodents captured between 1993 and 2019 that were positive for Arenavirus infection underwent Sanger and unbiased, Illumina-based high-throughput sequencing, which yielded 5 complete and 88 partial Mammarenaviruses genomes. Previously, 11 genomes representing four species of New World arenavirus Clade C existed in public records. This work has generated 13 novel genomes, expanding the New World arenavirus Clade C to 24 total genomes. Additionally, two genomes exhibit sufficient genetic diversity to be considered a new species, as per ICTV guidelines (proposed name Mammarenavirus vellosense). The 13 novel genomes exhibited reassortment between the small and large segments in New World Mammarenaviruses. This work demonstrates that Clade C Mammarenavirus infections circulate broadly among Necromys species in the Argentine Hemorrhagic Fever endemic area; however, the risk for Clade C Mammarenavirus human infection is currently unknown.

LASIK is associated with early cataract surgery in healthy patients.

PURPOSE: To evaluate the association between LASIK and early cataract phacoemulsification surgery (PE). METHODS: A matched case-control study was conducted. Cases were otherwise healthy adults with a history of LASIK. Groups were paired according to corrected-distance visual acuity (CDVA), axial length, and cataract grade. RESULTS: A total of 213 patients were included. 85 patients were classified as post-LASIK group and 128 as controls. The mean age at the time of LASIK was 42.32 ± 9.24 years. The mean CDVA before PE was 0.29 ± 0.19 Log MAR in post-LASIK group and 0.34 ± 0.22 Log MAR in controls (p = 0.07). The mean axial length was 23.99 ± 1.78 mm in post-LASIK group and 23.62 ± 0.98 mm in controls (p = 0.085). The mean nuclear cataract grading was 1.36 in post-LASIK group and 1.47 in controls (p = 0.34). The mean age at the time of PE was 60.18 ± 7.46 years in post-LASIK group and 67.35 ± 9.28 in controls (p < 0.0005). The difference between the mean age of LASIK and the mean age of PE was 17.85 ± 5.72 years. There was a positive association between the post-LASIK group and the age of PE ≤ 55 years (OR: 4.917, 95% CI: 2.21-10.90, p < 0.001). CONCLUSION: LASIK may be associated with early PE. Patients with LASIK had a 7-year earlier PE compared to a matched control group.

TRPV4 Activation during Guinea Pig Airway Smooth Muscle Contraction Promotes Ca2+ and Na+ Influx.

Airway smooth muscle (ASM) contraction is determined by the increase in intracellular Ca2+ concentration ([Ca2+]i) caused by its release from the sarcoplasmic reticulum (SR) or by extracellular Ca2+ influx. Major channels involved in Ca2+ influx in ASM cells are L-type voltage-dependent Ca2+ channels (L-VDCCs) and nonselective cation channels (NSCCs). Transient receptor potential vanilloid 4 (TRPV4) is an NSCC recently studied in ASM. Mechanical stimuli, such as contraction, can activate TRPV4. We investigated the possible activation of TRPV4 by histamine (His)- or carbachol (CCh)-induced contraction in guinea pig ASM. In single myocytes, the TRPV4 agonist (GSK101) evoked an increase in [Ca2+]i, characterized by a slow onset and a plateau phase. The TRPV4 antagonist (GSK219) decreased channel activity by 94%, whereas the Ca2+-free medium abolished the Ca2+ response induced by GSK101. Moreover, GSK101 caused Na+ influx in tracheal myocytes. GSK219 reduced the Ca2+ peak and the Ca2+ plateau triggered by His or CCh. TRPV4 blockade shifted the concentration-response curve relating to His and CCh to the right in tracheal rings and reduced the maximal contraction. Finally, the activation of TRPV4 in single myocytes increased the Ca2+ refilling of the SR. We conclude that contraction of ASM cells after stimulation with His or CCh promotes TRPV4 activation, the subsequent influx of Ca2+ and Na+, and the opening of L-VDCCs. The entry of Ca2+ into ASM cells via TRPV4 and L-VDCCs contributes to optimal smooth muscle contraction.

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.

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

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

Fuchs endothelial corneal dystrophy: an updated review.

PURPOSE: The present review will summarize FECD-associated genes and pathophysiology, diagnosis, current  therapeutic approaches, and future treatment perspectives. METHODS: Literature review. RESULTS: Fuchs' endothelial corneal dystrophy (FECD) is the most common bilateral corneal dystrophy and accounts for one-third of all corneal transplants performed in the US. FECD is caused by a combination of genetic and non-heritable factors, and there are two types: early-onset FECD, which affects individuals from an early age and is usually more severe, and late-onset FECD, which is more common and typically manifests around the age of 40. The hallmark findings of FECD include progressive loss of corneal endothelial cells and the formation of focal excrescences (guttae) on the Descemet membrane. These pathophysiological changes result in progressive endothelial dysfunction, leading to a decrease in visual acuity and blindness in later stages. The present review will summarize FECD-associated genes and pathophysiology, diagnosis, current therapeutic approaches, and future treatment perspectives. CONCLUSION: With the characterization and understanding of FECD-related genes and ongoing research into regenerative therapies for corneal endothelium, we can hope to see more significant improvements in the future in the management and care of the disease.

Enhancing Ocular Surface in Dry Eye Disease Patients: A Clinical Evaluation of a Topical Formulation Containing Sesquiterpene Lactone Helenalin.

The aim of this work was to assess the tolerability, safety, and efficacy of an ophthalmic topical formulation containing helenalin from Arnica montana and hyaluronic acid 0.4% (HA) in patients with mild-to-moderate Dry Eye Disease (DED) exhibiting positive Matrix Metalloproteinase 9 (MMP-9) test results. Tolerability and safety were evaluated in 24 healthy subjects. Participants were instructed to apply one drop of the formulation three times a day in the study eye, for 2 weeks, followed by a clinical follow-up of 21 days. Efficacy was studied in 48 DED patients randomized into Study (Group 1/receiving the studied formulation) or Control (Group 2/Receiving HA 0.4% eye lubricant) groups for 1 month. Assessments included an MMP-9 positivity test, conjunctival impression cytology (CIC), Ocular Surface Disease Index (OSDI), non-invasive film tear breakup time (NIBUT), non-invasive average breakup time (NIAvg-BUT), ocular surface staining, Schirmer's test, and meibomiography. A crossover design with an additional 1-month follow-up was applied to both groups. Healthy subjects receiving the studied formulation exhibited good tolerability and no adverse events. Regarding the efficacy study, Group 1 exhibited a statistically significant reduction in the MMP-9 positivity rate compared to Group 2 (p < 0.001). Both Group 1 and Group 2 exhibited substantial improvements in OSDI and NIBUT scores (p < 0.001). However, Group 1 demonstrated a significant improvement in NI-Avg-BUT and Schirmer's test scores (p < 0.001), whereas Group 2 did not (p > 0.05). Finally, after the crossover, the proportion of MMP-9-positive subjects in Group 1 increased from 25% to 91.6%, while Group 2 showed a significant decrease from 87.5% to 20.8%. Overall, the topical formulation containing sesquiterpene helenalin from Arnica montana and hyaluronic acid was well tolerated and exhibited a favorable safety profile. Our formulation reduces DED symptomatology and modulates the ocular surface inflammatory process; this is evidenced by the enhancement of CIC, the improvement of DED-related tear film status, and the reduction of the MMP-9 positivity rate.