Clinical outcomes of traumatic globe rupture in corneal graft patients.

PURPOSE: This study reports the mechanisms, complications and graft survival following sight-threatening traumatic globe rupture in patients having previously undergone corneal transplantation in the same eye. METHODS: A retrospective, observational, single-center consecutive cohort study at the Royal Victoria Infirmary, Newcastle upon Tyne, UK over a 20-year period. Medical records and Newcastle Corneal Transplantation Service electronic database (eNCTS) review was undertaken of all consecutive patients who underwent corneal transplantation with a history of traumatic globe rupture. Main outcome measures include mechanism of injury, final best-corrected distance visual acuity (BCDVA), graft survival and complications. RESULTS: A total of 921 keratoplasties were undertaken between 1997 and 2017 with 24 (3.0%) patients identified with a history of traumatic globe rupture. A bimodal relationship of age and mechanism of trauma was observed. The mean age (SD) of individuals reporting cause as a fall was 71.5 (14.8) years, and 45.3 (20.8) years (P < 0.05) amongst individuals reporting accidental trauma or assault. The pre- and post-trauma mean (SD) LogMAR BCDVA was 0.6 (0.9) and 1.7 (1.0), respectively (P = 0.001). The overall graft-failure rate was 60.9% (11 grafts) during a mean (SD) follow-up period of 3.5 (4.1) years. Globe rupture with lens damage was associated with poorer final BCDVA (P < 0.05). CONCLUSIONS: This study represents the first published series from England for this type of patient cohort. Overall visual outcomes were poor with a bimodal relationship of age and mechanism of trauma. Worse prognostic factors included lens and posterior segment complications. Re-grafting in these select group of patients may prove valuable.

Accelerated Corneal Crosslinking to Arrest Progression of Corneal Ectasia: A Prospective Multicenter Study.

OBJECTIVES: To report the results of epithelium-off accelerated corneal collagen crosslinking (accelerated corneal crosslinking [ACXL]) in patients with progressive keratoconus. METHODS: This prospective, nonrandomized, noncomparative, interventional, multicenter clinical study included all patients who underwent ACXL, either continuous (c-ACXL; 9 mW/cm 2 , 10', 5.4 J/cm 2 ) or pulsed (p-ACXL; 2″ON/1″OFF, 30 mW/cm 2 , 4.5', 5.4 J/cm 2 ) between January 2014 and May 2017. Best-corrected visual acuity, sphere, cylinder, spherical equivalent, and topographical keratometry data were collected preoperatively and at 1, 3, 6, 12, 18, and 24 months postoperatively. RESULTS: Ninety-six eyes of 78 patients were included. The mean age was 20.8±4.4 years (14-33) for c-ACXL and 26.7±7.7 years (12-37) for p-ACXL. The mean best-corrected visual acuity was 0.4±0.4 for c-ACXL and 0.01±0.1 for p-ACXL preoperatively, and 0.3±0.3 ( P =0.0014) and -0.01±0.1 ( P =0.1554), respectively, at the last follow-up. The subjective sphere and spherical equivalent did not show statistically significant differences between the time points ( P >0.05). The subjective cylinder showed significant differences ( P =0.0013 for c-ACXL; P =0.0358 for p-ACXL). Keratometric values (K steep , K flat , and SimK) remained stable, with no statistically significant differences ( P >0.05). No major complications were noted. CONCLUSIONS: Both c-ACXL and p-ACXL are equally safe and effective ACXL protocols in stabilizing the progression of keratoconus and can be considered alternatives to the conventional Dresden protocol.

Corneal Neuropathic Pain: A Patient and Physician Perspective.

Corneal neuropathic pain (CNP) is a debilitating condition characterized by pain in the absence of a noxious stimulus. Symptoms such as ocular stinging, burning, photophobia, irritation, and a deep aching pain can be severe despite a seemingly normal ocular surface on examination. CNP may develop due to either peripheral or central sensitization. Peripheral sensitization develops due to aberrant regeneration of corneal nociceptors and nerve fibers as a result of corneal injury or disease of peripheral corneal nerves. Whereas, central sensitization develops due to upregulation of excitatory neurotransmitters as a result of chronic inflammation, which leads to amplification of neuronal response to stimuli. Unfortunately, due to the disparity in severity of symptomology and the observable signs on examination, patients' symptoms are commonly thought to be "psychological" or "functional", and patients report feeling ignored and neglected. Additionally, diagnosis is often delayed which adversely affects patient outcomes. Research to date has focused on the scientific aspects of corneal neuropathic pain: its pathophysiology, epidemiology, investigations, and management. Research into the patient personal experience and the challenges faced by individual patients and their clinicians is lacking. We present the patient and physician perspective on the journey of both patients in order to provide insights into the challenges faced by patients and physicians in the diagnosis, assessment, and management of corneal neuropathic pain.

Corneal neuropathic pain is a rare disease that causes patients to experience severe eye pain without a painful stimulus. Patients often experience one or more symptoms, such as ocular stinging, burning, irritation, photophobia, and deep aching pains even though ophthalmologists cannot see any abnormality when they examine the eyes. Due to a significant lack of awareness and understanding of the condition, diagnosis is often delayed and patients are left feeling ignored or neglected. Research to date has focused on the scientific aspects of corneal neuropathic pain such as what causes it, the tests doctors use to diagnose it, and the best treatments to manage it. In this article, we present the patient and physician perspective, an understanding of which we believe can improve the care that patients receive and can promote awareness and understanding of the condition, facilitating early diagnosis and treatment.

Animal Models for Limbal Stem Cell Deficiency: A Critical Narrative Literature Review.

This literature review will provide a critical narrative overview of the highlights and potential pitfalls of the reported animal models for limbal stem cell deficiency (LSCD) and will identify the neglected aspects of this research area. There exists significant heterogeneity in the literature regarding the methodology used to create the model and the predefined duration after the insult when the model is supposedly fully fit for evaluations and/or for testing various therapeutic interventions. The literature is also replete with examples wherein the implementation of a specific model varies significantly across different studies. For example, the concentration of the chemical, as well as its duration and technique of exposure in a chemically induced LSCD model, has a great impact not only on the validity of the model but also on the severity of the complications. Furthermore, while some models induce a full-blown clinical picture of total LSCD, some are hindered by their ability to yield only partial LSCD. Another aspect to consider is the nature of the damage induced by a specific method. As thermal methods cause more stromal scarring, they may be better suited for assessing the anti-fibrotic properties of a particular treatment. On the other hand, since chemical burns cause more neovascularisation, they provide the opportunity to tap into the potential treatments for anti-neovascularisation. The animal species (i.e., rats, mice, rabbits, etc.) is also a crucial factor in the validity of the model and its potential for clinical translation, with each animal having its unique set of advantages and disadvantages. This review will also elaborate on other overlooked aspects, such as the anaesthetic(s) used during experiments, the gender of the animals, care after LSCD induction, and model validation. The review will conclude by providing future perspectives and suggestions for further developments in this rather important area of research.

NAGPKin: Nucleation-and-growth parameters from the kinetics of protein phase separation.

The assembly of biomolecular condensate in eukaryotic cells and the accumulation of amyloid deposits in neurons are processes involving the nucleation and growth (NAG) of new protein phases. To therapeutically target protein phase separation, drug candidates are tested in in vitro assays that monitor the increase in the mass or size of the new phase. Limited mechanistic insight is, however, provided if empirical or untestable kinetic models are fitted to these progress curves. Here we present the web server NAGPKin that quantifies NAG rates using mass-based or size-based progress curves as the input data. A report is generated containing the fitted NAG parameters and elucidating the phase separation mechanisms at play. The NAG parameters can be used to predict particle size distributions of, for example, protein droplets formed by liquid-liquid phase separation (LLPS) or amyloid fibrils formed by protein aggregation. Because minimal intervention is required from the user, NAGPKin is a good platform for standardized reporting of LLPS and protein self-assembly data. NAGPKin is useful for drug discovery as well as for fundamental studies on protein phase separation. NAGPKin is freely available (no login required) at https://nagpkin.i3s.up.pt.

First report of Lasiodiplodia brasiliensis causing root rot in melon plants in northeastern Brazil.

Melon (Cucumis melo L.) is the second most exported fruit in Brazil with an annual production of 27.5 million tons (FAO 2023). From September 2019 through February 2020, 50-day-old melon plants started showing root rot symptoms (dark-brow necrotic zones in their roots that extended to the collar zone) in northeastern Brazil, 30% of the plants in the fields were affected by the disease. The fields are in clay soil where melon, in monoculture, is produced all year long with three cycles of the culture per year. A total of 132 samples from "Yellow" and "Cantaloupe" cultivars were collected from four melon fields (4°59'45.3"S, 37°33'39.7"W; 4°57'10.2"S, 37°31'37.1"W; 5°38'17.9"S, 37°56'27.7"W; and 5°00'25.5"S, 37°23'55.3"W). Small pieces of diseased tissues were surface disinfested in 70% ethanol for 30 sec, in 2% sodium hypochlorite for 1 min, washed in sterilized distilled water, plated on a PDA Petri dishes with tetracycline (0.05g/L), and incubated for seven days at 28 ± 2 ºC. Nine representative isolates were selected for downstream analysis. Colonies were white and later became dark gray, pycnidia and conidia were produced after 30 days ofncubation at 25°C under near-UV light in water-agar medium. Conidia were hyaline when immature and dark brown when mature, ranging from cylindrical subovoid to ellipsoidal and septate to non-septate, and with an average size of 12.54 to 21.97 µm. The colonies were morphologically identified as Lasiodiplodia sp. (Phillips et al. 2013). Total DNA from the isolates was extracted and the ITS, TUB, and TEF-1α genes (Jayawardena et al. 2019) were partially amplified by PCR, Sanger sequenced, and deposited in Genbank: ITS (OM102511 to OM102520), TUB (OR062087 to OR062094 and OR062095), and TEF-1α (OP536826 to OP536835). Blastn analysis of the partial sequences ITS (519bp), TUB (388bp), and TEF-1α (315bp) showed 100% nucleotide similarity of the isolates with sequences of L. brasiliensis and L. theobromae from the GenBank. A phylogenetic tree was constructed using the Maximum Parsimony Analysis method. All nine isolates were grouped into the L. brasiliensis clade with 71% bootstrap support, confirming the isolates's identity. Pathogenicity assays were conducted in a greenhouse using the wooden toothpick inoculation method (Nogueira et al. 2019). "Goldex" Yellow melon seedlings were used in a completely randomized experimental design, with 10 treatments (9 isolates + Mock) and six replicates, with one plant per pot. Plants were inoculated 15 days after sowing, and disease severity was evaluated 50 days after inoculation. All nine isolates caused symptoms in the assessed melon plants. The fungus was reisolated from the lesions and looked morphologically identical to the inoculated fungus, fulfilling Koch's postulates. The pathogenicity test was repeated and yielded similar results. All samples in this study were provided by melon growers who were concerned about the high incidence of root rot disease in their plantations. More research needs to be conducted to determine the epidemiology and the extension of the economic impact caused by this pathogen to melons to develop strategies for disease control to properly assist the growers's concerns. This pathogen has been reported to cause disease in other crops in Brazil, e.g., watermelon (Alves et al. 2023) and apples (Martins et al. 2018). However, to the best of our knowledge, this is the first report of L. brasiliensis causing root rot in melons in Brazil.

Severe chemical eye injuries - clinical outcomes and associated socio-economic factors.

Aims: To describe clinical outcomes, management, and socio-economic impact of severe acute chemical eye injuries in a tertiary hospital. Methods: 37 patients required emergency admission to the Royal Victoria Infirmary eye ward between April 2013 and September 2015. Demographics, best corrected distance visual acuity (BCDVA), causative agent, degree of limbal stem cell deficiency (LSCD), management and socio-economic data were evaluated. Results: Mean age on admission was 34.5 years (SD 16.3; range 16-82); 30 males (81.1%); 22 bilateral (59.5%). Causative agent: alkali in 30 cases (81.1%); acid in three cases (8.1%); and unknown in four cases (10.8%). Fifteen cases (40.5%) were assaults, 12 (32.5%) work-related accidents, nine (24.3%) domestic accidents and one (2.7%) undetermined. Eleven patients (29.7%) were unemployed, 18 (48.6%) were labourers, three (8.1%) were students, three (8.1%) were retired and two (5.4%) were professionals. Mean admission time was five days (SD 3.2; range 1-12). Mean follow-up time was 170.5 days (range 1-946). Mean cost of admission was £2478 (range £274-5785). Five patients (13%; seven eyes) developed total or partial limbal stem cell deficiency, all being assaults. Conclusions: Main causative agent in our study was alkali, with young men in the working age being most frequently involved. Many patients required prolonged hospital admission and costly follow-up. The majority of cases were assaults, mostly occurring in unemployed patients. All the limbal stem cell deficiency cases were due to assaults. We believe that socio-economic factors play an important role in the cause, severity and cost of chemical eye injuries. Lay Summary: Acute chemical eye injuries have a significant and extensive impact on patients' visual function outcomes and vision-related quality of life, with consequent enormous burden to affected individuals, their families and society. We believe that by understanding the socio-economic environment, we may not only be able to enforce safety measures to tackle the increasing rate of severe chemical eye injuries in our community, but also to develop collaborative programmes with the community, educating the population on the seriousness of chemical eye injuries, and with the local authorities, trying to understand the clustering of assaults in areas and tackling the associated socio-economic risk factors, such as unemployment. Given the increasing rate of assaults using chemicals in recent times, it is also important to assess availability of adequate victim support programmes and develop good interaction with relevant local, regional and national authorities to ensure all aspects of community security service are in place to be able to address any potential deficiencies in line with police and home office guidelines. Keeping in mind that the best action plan is always prevention. However, when an ocular injury does occur it is evident that significant morbidity and visual sequelae can result and affect the socio-economic status of the victims despite our best current medical and surgical care.

Dupilumab induced ocular surface disease: A prospective case series.

PURPOSE: To identify the incidence, risk factors, demographics, and clinical profile of dupilumab-induced ocular surface disease (DIOSD) in patients with atopic dermatitis (AD), propose a standardised treatment protocol (STP) and evaluate the response. METHODS: Prospective case series of AD patients treated in the Dermatology Department, Royal Victoria Infirmary, Newcastle upon Tyne, UK developing ocular symptoms after commencing Dupilumab between September 2018 and February 2020. A standard history and examination protocol were used including subjective symptom severity grading and Ocular Surface Disease Index (OSDI) questionnaire on each visit. Standard treatment was prescribed, and response evaluated. RESULTS: 32 of 113 included patients (28.31%) developed DIOSD, of which 20 (62.5%) were referred to the Cornea Service. Median age was 38.0 years (IQR 26.8; range 19-74). Male to female ratio was 1:1. Average time to onset of ocular symptoms from starting dupilumab was 9.2 weeks (IQR 8.8; range 0.1-40). 90% patients had bilateral conjunctival inflammation and blepharitis at presentation. Significant improvement in the subjective severity scale and the median OSDI score (from 34.0 to 10.2) was noted in response to topical eye treatment. Dupilumab was discontinued in none. CONCLUSIONS: DIOSD is not uncommon although, with timely referral and appropriate topical treatment better clinical outcome and patient satisfaction can be achieved without the need to discontinue Dupilumab. Prior allergic conjunctivitis did not affect the incidence or severity of DIOSD. Further prospective studies with longer follow-up and more focus on possible disease mechanism such as goblet cell related changes and immune response are needed.

Outcomes of N-butyl-2-Cyanoacrylate Tissue Adhesive Application in Corneal Perforation Disorders: Consecutive Case Series.

INTRODUCTION: The purpose of this study was to report the success and long-term outcomes of cyanoacrylate tissue adhesive (CTA) application in the management of corneal perforation disorders. METHODS: This retrospective case series describes the profile and outcomes of eyes that underwent CTA for corneal perforation over an 11-year period from January 2009 until January 2020 at a tertiary eye centre in the United Kingdom. RESULTS: In total, 25 eyes underwent CTA application during the study period. Non-traumatic sterile corneal melt was responsible in more than half of the cases (56.0%; n = 14) followed by infection (32.0%; n = 8) and trauma (12.0%; n = 3). Median size of perforation was 2.0 mm (interquartile range, IQR 1.0-3.0). The most common anatomical location of corneal perforation was central (56.0%; n = 14). Ocular surface disease was seen in almost all eyes except two (92.0%; n = 23) with dry eye disease being the most common (48.0%; n = 12). Amongst 23 eyes that completed follow-up (median 27 months; IQR 9.5-46.5), single CTA application was successful in achieving intact globe in 13 (56.5%) eyes and repeat gluing sealed total of 20 (86.9%) eyes. Survival analysis showed cumulative success of 71.0% and 51.2% at 90 and 250 days, respectively. The CTA was retained in the eyes for median of 94.0 days (IQR 30.0-140.5). A total of five patients developed adverse events, including endophthalmitis (n = 2), following CTA application. CONCLUSIONS: CTA was highly effective in sealing corneal perforations in acute setting and showed moderate long-term success. However, multiple applications are often required.

Drug repurposing of dopaminergic drugs to inhibit ataxin-3 aggregation.

The accumulation of mutant ataxin-3 (Atx3) in neuronal nuclear inclusions is a pathological hallmark of Machado-Joseph disease (MJD), also known as Spinocerebellar Ataxia Type 3. Decreasing the protein aggregation burden is a possible disease-modifying strategy to tackle MJD and other neurodegenerative disorders for which only symptomatic treatments are currently available. We performed a drug repurposing screening to identify inhibitors of Atx3 aggregation with known toxicological and pharmacokinetic profiles. Interestingly, dopamine hydrochloride and other catecholamines are among the most potent inhibitors of Atx3 aggregation in vitro. Our results indicate that low micromolar concentrations of dopamine markedly delay the formation of mature amyloid fibrils of mutant Atx3 through the inhibition of the earlier oligomerization steps. Although dopamine itself does not cross the blood-brain barrier, dopamine levels in the brain can be increased by low doses of dopamine precursors and dopamine agonists commonly used to treat Parkinsonian symptoms. In agreement, treatment with levodopa ameliorated motor symptoms in a C. elegans model of MJD. These findings suggest a possible application of dopaminergic drugs to halt or reduce Atx3 accumulation in the brains of MJD patients.

Night eating syndrome among university students: are aspects of academic life associated with eating disorders? / Síndrome do comer noturno entre estudantes universitários: aspectos da vida acadêmica estariam associados ao distúrbio alimentar?

Introduction: the critical period in the lives of college adults implies lifestyle changes such as reducing physical activity and adopting unhealthy eating habits that can result in increased body fat. Thus, college students may represent a population at increased risk for Night Eating Syndrome. Objective: to analyze aspects of university students' academic life, work and housing that could be associated with Night Eating Syndrome. Methods: cross-sectional study carried out with 900 students from Architecture, Engineering, Medicine and Psychology courses at a higher education institution located in Cajazeiras, Paraíba, Brazil. Self-administered questionnaires were used for data collection: the Night Eating instrument Questionnaire (NEQ) to quantify Night Eating Syndrome (NCS) behaviors and a form for variables on demographic, health, academic life, work and housing aspects. Results: the prevalence of NES determined by the NEQ≥25 score was 16.8%. In the Engineering course, the prevalence of SCN was higher in women than in men, and in the Psychology course, it was higher in men than in women. Among students with a job and who lived at home, the prevalence of the syndrome was higher for those who worked in the afternoon and lower for those who worked at night. Conclusion: the prevalence of NES found among Brazilian university students was high (16.8%), particularly in two situations: (1) being enrolled in an undergraduate course with a predominance of students of the other sex; and (2) live with parents and work in the afternoon. These observations may be helpful in identifying subpopulations of students at increased risk for eating disorders.

Introdução: o período crítico da vida de adultos universitários implica mudanças do estilo de vida como a diminuição da atividade física e a adoção de hábitos alimentares pouco saudáveis que podem resultar em aumento da gordura corporal. Assim, estudantes universitários podem representar uma população com risco aumentado para a Síndrome do Comer Noturno. Objetivo: analisar aspectos da vida acadêmica, do trabalho e da moradia de estudantes universitários que poderiam se associar à Síndrome do Comer Noturno. Método: estudo transversal realizado com 900 estudantes dos cursos de Arquitetura, Engenharia, Medicina e Psicologia de uma instituição de ensino superior localizada em Cajazeiras, Paraíba, Brasil. Para a coleta de dados foram usados questionários autoaplicados: o instrumento Night Eating Questionnaire (NEQ) para quantificar comportamentos da Síndrome do Comer Noturno (SCN) e um formulário para variáveis sobre aspectos demográficos, de saúde, vida acadêmica, trabalho e moradia. Resultados: a prevalência da SCN determinada pelo escore NEQ≥25 foi 16,8%. No curso de Engenharia a prevalência da SCN foi maior nas mulheres em relação aos homens, e no curso de Psicologia, foi maior nos homens em relação as mulheres. Entre os estudantes com emprego e que moravam na casa dos pais, a prevalência da síndrome foi maior para aqueles que trabalham no período da tarde e menor para aqueles que trabalham à noite. Conclusão: a prevalência da SCN encontrada entre os estudantes universitários brasileiros foi alta (16,8%), particularmente em duas situações: (1) estar matriculado um curso de graduação com predominância de estudantes do outro sexo; e (2) morar com os pais e trabalhar no período da tarde. Estas observações podem ser úteis na identificação de subpopulações de estudantes com risco aumentado de distúrbios de alimentação

International survey on dry eye diagnosis by experts.

Purpose: To evaluate patterns and opinion from international experts with respect to dry eye disease (DED) diagnosis in clinical practice. Methods: An online survey was distributed to worldwide DED experts. The use of diagnosis tests was evaluated including: symptoms questionnaires, functional tests, tear stability, tear volume, tear composition, surface damage and inflammation, and eyelid assessment. After the subjective importance of symptoms, tear break up time (TBUT), non-invasive TBUT, Schirmer's test, tear meniscus height, tear osmolarity, tear metalloproteinase 9, blepharitis assessment and non-contact meibography was evaluated according to likert scale. Results: The survey was sent to 109 experts, and 77 completed the questionnaire (rate of response = 70.6%). Most of the participants were from North America (27%) and Europe (40%). A majority of respondents (73%) diagnose DED using clinical signs and symptoms, but not fulfilling a specific criteria. Seventy-six participants (98.7%) use symptoms questionnaires. All participants evaluate damage to ocular surface, and fluorescein staining is the most frequent method used (92%). Also, all the respondents perform meibomian gland and blepharitis assessment. On the other hand, only 69.8% evaluate tear composition, being osmolarity the most common test used (66.2%). Regarding to the importance of tests, TBUT (p = 0.002) and Schirmer's (p = 0.021) were found to be more important to experts from Europe than North America. No differences were found in any other test (p > 0.05). Conclusions: This survey offers updated and day-to-day diagnostic clinical practice by DED worldwide experts. The results highlight the importance of symptoms and clinical signs, but not necessarily following a strict criteria.

Differences in minimal disease knowledge of keratoconus patients: results from an international survey.

BACKGROUND/AIMS: The objective of this multicentre, multinational, prospective study was to assess the level of basic understanding that individuals with keratoconus possessed about their condition. METHODS: We recruited 200 active keratoconus patients who were under regular review, and cornea specialists established a standard of 'minimal keratoconus knowledge' (MKK) that included an understanding of the definition, risk factors, symptoms and treatment options for the condition. We collected data from each participant regarding their clinical characteristics, highest level of education, (para)medical background and experiences with keratoconus within their social circle, and calculated the percentage of MKK attained by each patient. RESULTS: Our findings revealed that none of the participants met the MKK standard, with the average MKK score being 34.6% and ranging from 0.0% to 94.4%. Furthermore, our study showed that patients with a university degree, previous surgical intervention for keratoconus or affected parents had a higher MKK. However, age, gender, disease severity, paramedical knowledge, disease duration and best-corrected visual acuity did not significantly affect the MKK score. CONCLUSIONS: Our study demonstrates a concerning lack of basic disease knowledge among keratoconus patients in three different countries. The level of knowledge exhibited by our sample was only one-third of what cornea specialists would typically anticipate from patients. This highlights the need for greater education and awareness campaigns surrounding keratoconus. Further research is needed to determine the most efficient approaches for enhancing MKK and subsequently improving the management and treatment of keratoconus.

Future directions in managing aniridia-associated keratopathy.

Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive loss of corneal transparency and thereby loss of vision. Currently, there is no approved therapy to delay or prevent its progression, and clinical management is challenging because of phenotypic variability and high risk of complications after interventions; however, new insights into the molecular pathogenesis of AAK may help improve its management. Here, we review the current understanding about the pathogenesis and management of AAK. We highlight the biological mechanisms involved in AAK development with the aim to develop future treatment options, including surgical, pharmacological, cell therapies, and gene therapies.

Effects of consumption of mauritia flexuosa fruits on renal and hepatic functions in growing rats

INTRODUCTION: Previous studies have reported that buriti (Mauritia flexuosa L. f.) is a typical fruit from the Brazilian cerrado ecosystem and an important food source for low-income populations. Its composition is rich in carotenoid polyphenols, monounsaturated fatty acids, and ascorbic acid. However, studies on the biological effects resulting from the consumption of this fruit are scarce. OBJECTIVE: To evaluate the effects of a diet supplemented with buriti (Mauritia flexuosa L. f.) on kidney and liver functions in growing rats. METHODS: Determination of centesimal composition, carotenoids, and fatty acids content for buriti pulp, standard chow, and butiti-supplemented chow were performed. Then, Wistar rats of both sexes were fed a standard diet or supplemented with buriti pulp. Blood samples were collected at the end of the experiment to determine biochemical parameters. The unpaired t-test was applied, and differences were considered significant when p<0.05. RESULTS: A diet enriched with buriti pulp did not interfere with kidney function and most markers of liver function in animals. Alkaline phosphatase showed significantly higher plasma concentration in female rats, and albumin and uric acid showed lower concentrations in male rats in both experimental groups. CONCLUSION: The changes observed in biochemical markers did not provide evidence of adverse effects of buriti pulp supplementation on liver function. Thus, the intake of buriti pulp can be encouraged as it is a low-cost food source for the general population.

Minimally invasive corneal neurotization for neurotrophic keratopathy: The potential effect of age, denervation chronicity and lesion location.

Purpose: Neurotrophic keratopathy (NK) is an uncommon but challenging clinical condition characterized by altered corneal nerves and sensation leading to corneal damage. Corneal neurotization, a surgical technique that aims to "re-innervate" the cornea, has gained increasing popularity in view of the potential to permanently improve or even restore the normal corneal sensation. In this study, we aimed to report the outcomes of two cases of NK that underwent indirect minimally invasive corneal neurotization (MICN) with a sural nerve autograft, and to provide plausible explanations for the observed clinical outcomes. Observations: This was an interventional case series of two patients who underwent MICN for severe unilateral NK. The MICN technique was adapted from the technique originally described by Elbaz et al., in 2014. Clinical severity of NK was graded according to Mackie's grading system. Corneal sensation was measured using the Cochet-Bonnet esthesiometer (0-60mm) and corneal nerves were examined using in vivo confocal microscopy (IVCM) with Heidelberg HRT3 Rostock Corneal Module. Patient 1 was a 70-year-old man with a right grade III NK following trigeminal nerve decompression for trigeminal neuralgia. Patient 2 was a 62-year-old man with a left grade II NK following a left-sided acoustic neuroma resection. The denervation time was 23 years for both patients. Following the MICN surgery, none of the patients achieved sustained improvement in the corneal sensation (though patient 1 achieved a transient improvement in central corneal sensation to 20mm at 4 months' postoperative before returning to 0mm at 6 months' postoperative). IVCM did not reveal any changes in the corneal nerve density and morphology post-MICN. Conclusions and Importance: Based on our observations and the literature, we postulate that long denervation time, proximal injury to the trigeminal nerve and older patient age may serve as poor prognostic factors for MICN. As CN is being increasingly adopted in clinical practice for treating NK, understanding of these potential factors will facilitate better risk-benefit stratification and patient counselling. Future larger studies are required to elucidate these findings.

Understanding Ocular Surface Inflammation in Tears Before and After Autologous Cultivated Limbal Epithelial Stem Cell Transplantation.

INTRODUCTION: We aimed to determine the expression of inflammatory cytokines in the tears of patients with unilateral total limbal stem cell deficiency (TLSCD) caused by chemical burns before and after autologous cultivated limbal epithelial stem cell transplantation (CLET). METHODS: Tear samples were collected from both eyes of 23 patients with unilateral TLSCD and 11 healthy controls, at fixed timepoints before and after CLET. Dissolved molecules were extracted from Schirmer's strips using a standardised method and analysed on an array plate of ten inflammatory cytokines (V-Plex Proinflammatory Panel 1 Human Kit, MSD). RESULTS: IL1ß expression was significantly elevated in the TLSCD eye compared with the unaffected eye at baseline (p < 0.0001) but decreased to normal 3 months post-CLET (p = 0.22). IL6 and IL8 were unaffected at baseline but significantly elevated in the TLSCD eyes at 1 month post-CLET (p = 0.001 and p < 0.0001, respectively). IL6 returned to normal at 3 months and IL8 at 6 months post-CLET. There was a significant renewed increase in IL1ß, IL6 and IL8 expression at 12 months post-CLET (p < 0.0001, p = 0.0001 and p = 0.0003, respectively). IFNγ, IL10 and IL12p70 expression were significantly reduced in both eyes of patients with unilateral TLSCD at all timepoints. CONCLUSION: IL1ß is a specific marker of inflammation in TLSCD eyes that could be therapeutically targeted pre-CLET to improve stem cell engraftment. At 12 months post-CLET the spike in levels of IL1ß, IL6 and IL8 coincides with cessation of topical steroids, suggesting ongoing subclinical inflammation. We therefore recommend not discontinuing topical steroid treatment in cases where penetrating keratoplasty is indicated; however, further investigation is needed to ascertain this. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials Database (EuDRACT 2011-000608-16); ISRCTN (International Standard Randomised Controlled Trial Number (isrctn51772481).

Aggressivity of Different Fusarium Species Causing Fruit Rot in Melons in Brazil.

Brazil is one of the largest melon (Cucumis melo) producers in the world and most of the production is exported to international markets. Currently, over 15% of Brazilian melon shipments are lost during export transportation due to Fusarium fruit rot, which is jeopardizing the livelihood of Brazilian melon producers. We focused on understanding the aggressivity of five species of Fusarium causing fruit rot on the main types of melon produced in Brazil. We also investigated the correlation between pathogenicity and fruit quality. Experiments were performed under a completely randomized experimental design, in a 5 × 8 factorial scheme, using two methods for inoculation: deposition of discs of culture media containing fungal structures and deposition of spore suspensions in needle-punctured lesions. The fungal species used were Fusarium falciforme, F. sulawesiense, F. pernambucanum, F. kalimantanense, and Fusarium sp. Fruits of two hybrids from four types of melons, canary (Goldex and Gold Mine), piel de sapo (Grand Prix and Flecha Verde), galia (McLaren and DRG3228), and cantaloupe (SV1044MF and Bonsai), were used. Disease severity was assessed by measuring the lesions, disease severity index, fruit firmness, and degrees Brix of fruits. The five Fusarium species caused rot in the fruits of all melon hybrids studied and the aggressivity of those fungal species varied with the type and hybrid. Fruits of the hybrids McLaren and Bonsai presented the largest lesions among all melon hybrids, and hybrids of canary type (Gold Mine and Goldex) were the most tolerant to rot caused by the Fusarium species investigated. Furthermore, the greater the severity of Fusarium fruit rot, the lower the pulp firmness of the fruits, but degrees Brix did not correlate with the onset of the disease.

National survey of corneal cross-linking (CXL) practice patterns in the United Kingdom during 2019.

OBJECTIVE: To provide an insight into trends in corneal cross-linking (CXL) practice in the UK, including criteria for progression of corneal ectasia, identification of patients for CXL, the CXL procedure itself and post-operative management. METHODS: All ophthalmologist members of the UK Cross-linking (UK-CXL) Consortium were invited to complete an online survey about CXL practice for the year 2019. The data collected was anonymised by site and analysed with descriptive statistics. RESULTS: Responses were received from 16 individual CXL centres (16/38; 42% response rate) and the data represented ~2,000 CXL procedures performed in the UK in 2019. The commonest indication for CXL was progressive keratoconus. Between centres, there were variations in diagnostic evaluation, patient selection for CXL, the CXL procedure and the pre- and post-operative monitoring of patients. CONCLUSION: Consistent with the wide number of CXL treatment techniques described in the published literature world-wide, variations in the monitoring of corneal ectasia, indications for CXL, CXL practice and post-CXL follow-up were found to exist between UK-based CXL centres.