Decoding the mechanism governing the structural stability of wheat germ agglutinin and its isolated domains: A combined calorimetric, NMR, and MD simulation study.

Wheat germ agglutinin (WGA) demonstrates potential as an oral delivery agent owing to its selective binding to carbohydrates and its capacity to traverse biological membranes. In this study, we employed differential scanning calorimetry and molecular dynamics simulations to comprehensively characterize the thermal unfolding process of both the complete lectin and its four isolated domains. Furthermore, we present the nuclear magnetic resonance structures of three domains that were previously lacking experimental structures in their isolated forms. Our results provide a collective understanding of the energetic and structural factors governing the intricate unfolding mechanism of the complete agglutinin, shedding light on the specific role played by each domain in this process. The analysis revealed negligible interdomain cooperativity, highlighting instead significant coupling between dimer dissociation and the unfolding of the more labile domains. By comparing the dominant interactions, we rationalized the stability differences among the domains. Understanding the structural stability of WGA opens avenues for enhanced drug delivery strategies, underscoring its potential as a promising carrier throughout the gastrointestinal environment.

Neurotrophic keratopathy: General features and new therapies.

Neurotrophic keratopathy is an uncommon degenerative corneal disorder characterized by compromised corneal sensory innervation, resulting in the formation of epithelial defects and nonhealing corneal ulcers. Various treatment modalities are available to stabilize disease progression, improve patient well-being, and prevent vision loss. For eligible patients, medical and surgical reinnervation have emerged as pioneering therapies, holding promise for better management. This article presents a comprehensive review of the disease, providing an update relevant to ophthalmologists on pathogenesis, diagnosis, treatment options, and novel therapies targeting pathophysiological pathways.

Adaptation and learning as strategies to maximize reward in neurofeedback tasks.

Introduction: Adaptation and learning have been observed to contribute to the acquisition of new motor skills and are used as strategies to cope with changing environments. However, it is hard to determine the relative contribution of each when executing goal directed motor tasks. This study explores the dynamics of neural activity during a center-out reaching task with continuous visual feedback under the influence of rotational perturbations. Methods: Results for a brain-computer interface (BCI) task performed by two non-human primate (NHP) subjects are compared to simulations from a reinforcement learning agent performing an analogous task. We characterized baseline activity and compared it to the activity after rotational perturbations of different magnitudes were introduced. We employed principal component analysis (PCA) to analyze the spiking activity driving the cursor in the NHP BCI task as well as the activation of the neural network of the reinforcement learning agent. Results and discussion: Our analyses reveal that both for the NHPs and the reinforcement learning agent, the task-relevant neural manifold is isomorphic with the task. However, for the NHPs the manifold is largely preserved for all rotational perturbations explored and adaptation of neural activity occurs within this manifold as rotations are compensated by reassignment of regions of the neural space in an angular pattern that cancels said rotations. In contrast, retraining the reinforcement learning agent to reach the targets after rotation results in substantial modifications of the underlying neural manifold. Our findings demonstrate that NHPs adapt their existing neural dynamic repertoire in a quantitatively precise manner to account for perturbations of different magnitudes and they do so in a way that obviates the need for extensive learning.

Oral administration of a recombinant modified RBD antigen of SARS-CoV-2 as a possible immunostimulant for the care of COVID-19.

BACKGROUND: Developing effective vaccines against SARS-CoV-2 that consider manufacturing limitations, equitable access, and acceptance is necessary for developing platforms to produce antigens that can be efficiently presented for generating neutralizing antibodies and as a model for new vaccines. RESULTS: This work presents the development of an applicable technology through the oral administration of the SARS-CoV-2 RBD antigen fused with a peptide to improve its antigenic presentation. We focused on the development and production of the recombinant receptor binding domain (RBD) produced in E. coli modified with the addition of amino acids extension designed to improve antigen presentation. The production was carried out in shake flask and bioreactor cultures, obtaining around 200 mg/L of the antigen. The peptide-fused RBD and peptide-free RBD proteins were characterized and compared using SDS-PAGE gel, high-performance chromatography, and circular dichroism. The peptide-fused RBD was formulated in an oil-in-water emulsion for oral mice immunization. The peptide-fused RBD, compared to RBD, induced robust IgG production in mice, capable of recognizing the recombinant RBD in Enzyme-linked immunosorbent assays. In addition, the peptide-fused RBD generated neutralizing antibodies in the sera of the dosed mice. The formulation showed no reactive episodes and no changes in temperature or vomiting. CONCLUSIONS: Our study demonstrated the effectiveness of the designed peptide added to the RBD to improve antigen immunostimulation by oral administration.

Risk Factors Associated with Diabetic Retinopathy with and without Macular Edema in Recently Diagnosed Patients with Type 2 Diabetes.

Purpose: To evaluate the risk factors associated with diabetic macular edema (DME) in patients with a recent type 2 diabetes mellitus (T2DM) diagnosis. Patients and Methods: We conducted a case-control study at a third-level hospital in Mexico City. We enrolled patients ≥18 years old, with T2DM less than five years of diagnosis, without disabling complications, and non-smokers. The control group was patients with diabetic retinopathy and without macular edema (DR-DME). Cases were patients with DR+DME. We measured fasting glucose, creatinine, lipid profile, urinary albumin/creatinine ratio (ACR), and HbA1c. An ophthalmological examination consisted of visual acuity measurement, digital three-field fundus photography with an automatic non-mydriatic camera, slit lamp, and Optical coherence tomography (OCT) examination. Results: 183 and 61 patients with DR-DME and DR+DME, respectively, were included in the analysis. The prevalence of mild DR was higher in the DR-DME group, but the frequencies of moderate and severe retinopathy were higher in the DR+DME group. Patients in the DR-DME group had better vision than those in the DR+DME group. Logistic regression analysis revealed that age (OR, 1.07), HbA1c (OR, 1.19), and Albumin-to-Creatinine Ratio (ACR) > 30 mg/g (OR, 3.37) were associated with an increased possibility of DME compared to DR-DME. Conclusion: Our study provides insights into the association between risk factors and DME. We found a statistically strong association between HbA1c levels, age, and ACR. Patients with poor metabolic control should undergo an extensive medical examination to screen for DME, which may be related to the chronicity of DM and renal damage.

Attitudes About the Human Papillomavirus Vaccine Among Patients With and Without Cervical Dysplasia.

OBJECTIVES: The aims of the study are to examine the perception of the human papillomavirus (HPV) vaccine among those with and without a history of cervical dysplasia and to examine perceptions of the vaccine for their children. MATERIALS AND METHODS: Patients were recruited to complete a survey about the HPV vaccine for both themselves and their children. Patients in a colposcopy clinic with a history of abnormal cervical cytology and patients in a benign gynecology clinic without a history of abnormal cervical cytology were recruited. Participants' medical records were reviewed. Demographics and survey answers were described, and Fisher exact test was used to compare the groups. RESULTS: One hundred eighty-three patients participated: 73 in colposcopy clinic and 110 in benign clinic. The majority self-identified as Black (74% colposcopy, 71% benign, p = .588) and reported an income less than $39,000 a year (77% colposcopy, 65% benign, p = .089). Fifty-six percent in benign clinic agreed the HPV vaccine is a good way to protect oneself from disease compared with 48% in colposcopy clinic ( p = .022). When examining results based on cytology, fewer patients in the highest-grade cytology group agreed the vaccine was effective (30% high-grade, 48% normal, 57% low-grade, p = .027) or a good way to protect themselves from disease (29% high-grade, 53% normal, 62% low-grade, p = .002). There was otherwise no statistically significant difference between the groups on questions regarding self or child vaccination. CONCLUSIONS: In a majority Black, low-income population, patients without a history of abnormal cervical cytology have more favorable perceptions of the HPV vaccine's effectiveness in preventing disease. Those with the highest-grade cytology had more negative perceptions of the vaccine's effectiveness and protectability.

Perceived importance of weight loss and exercise among endometrial cancer survivors with overweight or obesity: Implications for lifestyle modification interventions.

Objective: Type 1 endometrial cancer (EC) survivors who are overweight or obese are at increased risk of comorbidities and reduced quality of life. Lifestyle modification interventions (e.g., healthy eating, exercise) may help these women reduce excess weight and improve their quality of life. However, existing interventions have shown limited success. Guided by Self-Determination Theory, the proposed study sought to identify factors associated with perceived importance of weight loss and exercise as well as interest in lifestyle modification interventions (components of extrinsic and intrinsic motivation) among EC survivors with overweight or obesity to inform future intervention development. Methods: One hundred type 1 EC survivors [body mass index (BMI) ≥ 25 kg/m2] completed a cross-sectional survey assessing sociodemographics, medical factors, exercise, risk perceptions and provider communication, quality of life, barriers to dieting and exercise, perceived importance of healthy lifestyles, and desired intervention content. Results: EC survivors who were aware obesity is a risk factor for EC were significantly more likely to perceive weight loss as important and were interested in weight loss programs and receiving information about exercise (ps < 0.05). Additionally, EC survivors who reported their provider discussed the importance of a healthy weight after their diagnosis were significantly more likely to perceive exercise as important and were interested in receiving dieting information. Conclusions: EC survivors expressed interest in lifestyle modification interventions. Increasing awareness about the risk of obesity and provider discussions about healthy weight during routine appointments may motivate EC survivors to engage in lifestyle modification interventions.

Importance and use of corneal biomechanics and its diagnostic utility.

The study of corneal biomechanics has become relevant in recent years due to its possible applications in the diagnosis, management, and treatment of various diseases such as glaucoma, keratorefractive surgery and different corneal diseases. The clinical biomechanical investigation has become of great importance in the setting of refractive surgery to identify patients at higher risk of developing iatrogenic ectasia. This review focuses on two of the technologies available for clinical use, the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, NY, USA) and the Corvis ST (Oculus Optikgergäte GmbH, Wetzlar, Germany). Both are non-contact tonometers that provided a clinical evaluation of corneal biomechanics. The fundamentals and main parameters of each device are described, as well as their use in eye surgery and the corneal biomechanical behavior in eye diseases. Finally, we will discuss the more recent Brillouin microscopy biomechanical analysis, and the integration Scheimpflug-based corneal tomography and biomechanical data with artificial intelligence to increase accuracy to detect risk of ectasia.

El estudio de la biomecánica corneal ha cobrado relevancia en los últimos años debido a sus posibles aplicaciones en el diagnóstico, el manejo y el tratamiento de diversas enfermedades, como glaucoma, cirugía queratorrefractiva y diferentes enfermedades corneales. La investigación de la biomecánica corneal es de mucha importancia en el contexto de cirugía refractiva, pues podría identificar pacientes en riesgo de desarrollar una ectasia corneal iatrogénica. Esta revisión se centra en dos de las tecnologías disponibles para uso clínico: el Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, NY, EE. UU.) y el Corvis ST (Oculus Optikgergäte GmbH, Wetzlar, Alemania). Ambos son tonómetros de no contacto que proporcionan una evaluación clínica de la biomecánica corneal. Se describen los fundamentos y los principales parámetros de cada dispositivo, así como su uso en cirugía ocular y el comportamiento biomecánico corneal en las enfermedades oculares. Finalmente, se mencionan los dispositivos más recientes de análisis biomecánico, como la microscopía de Brillouin, así como la integración de los datos biomecánicos y topográficos basados en Scheimpflug con la inteligencia artificial para aumentar la precisión en la detección del riesgo de ectasias.

Cogan syndrome: a case report and review of the literature.

Cogan syndrome is a rare disease whose etiology is still undetermined. It typically affects men and women between the second and fourth decade of life. We report a case of Cogan syndrome with ocular and audio-vestibular involvement as a systemic manifestation in a 31-year-old woman.

Use of Amniotic Membrane Transplant and Deep Anterior Keratoplasty in a Patient with Bilateral Acanthamoeba Infectious Keratitis: A Case Report.

The aim of this study was to report a case with the use of amniotic membrane transplant and deep anterior keratoplasty in a patient with bilateral Acanthamoeba infectious keratitis as a treatment. A 20-year-old male presented with bilateral Acanthamoeba keratitis (AK) who was initially diagnosed with herpetic keratitis receiving full antiviral and corticosteroid topical treatment without any improvement. Corneal biopsy was performed to confirm the suspected diagnosis, and Acanthamoeba stromal cysts were identified in the sample. Treatment was initiated with 0.02% chlorhexidine, 0.1% propamidine isethionate, neomycin, and tropicamide/phenylephrine. Symptoms and clinical improvement were achieved between the 8th and 10th weeks, so corticosteroids were initiated. Treatment was continued until we observed a poor response in the left eye; therefore, an epithelial scraping and amniotic membrane placement were performed. Lately, the right eye underwent a deep anterior lamellar keratoplasty. A challenging case of bilateral AK managed with topical medications, amniotic membrane, and corneal keratoplasty. The earlier the disease is diagnosed, the better the outcome. If the diagnosis is delayed, the amoebas have penetrated deep into the corneal stroma, and successful therapy becomes difficult. A surgical option can be an early solution with a good prognosis for these cases.

Comparison of mini-simple limbal epithelial transplantation and conjunctival-limbal autograft for the treatment of primary pterygium: a randomised controlled trial.

PURPOSE: The purpose of this double-masked, parallel randomised controlled trial was to compare the recurrence rate and other outcomes between conjunctival-limbal autograft (CLAu) and mini-simple limbal epithelial transplantation (mini-SLET) after excision of pterygium. METHODS: Eligibility criteria for participants was the presence of a primary nasal pterygium extending equally to or greater than two millimetres on the cornea on its horizontal axis from the nasal limbus. The participants were allocated into two groups (CLAu and mini-SLET) using simple randomisation with a table of random numbers. Participants and the outcome assessor were masked to the intervention. The study protocol is listed and available on https://clinicaltrials.gov (Identifier: NCT03363282). RESULTS: A total of 61 eyes were enrolled in the study, 33 underwent CLAu (group 1) and 28 mini-SLET (group 2), all eyes were analysed in each group. At 2, 3, 6 and 12 months the CLAu group exhibited a recurrence of 0%, 6.1%, 8.1% and 8.1%, while the mini-SLET exhibited a recurrence of 0%, 17.9%, 50% and 53.5% (p<0.05). There were no intraoperative or postoperative complications in either of the two groups. CONCLUSION: The findings of this study suggest that mini-SLET has a higher recurrence rate and provides no advantage over CLAu in the treatment of primary pterygium.

Ophthalmic findings in patients with autosomal recessive lamellar ichthyosis due to TGM1 mutations in an isolated population.

PURPOSE: To describe the ocular clinical characteristics of a group of Mexican patients with lamellar ichthyosis (LI) arising from TGM1 pathogenic variants. METHODS: Ophthalmological exploration, pedigree analysis and genetic screening were performed in patients with an established clinical diagnosis of lamellar ichthyosis from families located in a small community in the Southeast of Mexico. RESULTS: Nine patients with LI in five families were identified. There were six affected females. All patients (9/9) demonstrated eye lid abnormalities with eight patients showing lid margin abnormalities. Madarosis was present in only three individuals and corneal scarring was documented in two. All nine individuals carried biallelic TGM1 variants, either homozygously or as compound heterozygous. CONCLUSION: Ocular anomalies are common in individuals with TGM1-related LI. The occurrence of a variety of private or rare mutations hampers the identification of a genotype-phenotype correlation for ocular anomalies in this disorder.

Energy-saving pretreatments affect pelagic Sargassum composition and DNA metabarcoding reveals the microbial community involved in methane yield.

Sargassum spp. flood the Caribbean coastline, causing damage to the local economy and environment. Anaerobic digestion (AD) has been proposed as an attractive option for turning macroalgae into valuable resources. Sargassum spp. has a complex composition that affects the microbial composition involved in AD which generates a low methane yield. This study aimed to improve the methane yield of pelagic Sargassum, using different energy-saving pretreatments and identifying the microbial community associated with methane production. We applied different energy-saving pretreatments to algal biomass and assessed the methane yield using a biomethane potential (BMP) test. The microbial communities involved in the AD of the best- and worst-performing methanogenic systems were analyzed by high-throughput sequencing. The results showed that pretreatment modified the content of inorganic compounds, fibers, and the C:N ratio, which had a strong positive correlation with BMP. The water washing pretreatment resulted in the best methane yield, with an increase of 38%. DNA metabarcoding analysis revealed that the bacterial genera Marinilabiliaceae_uncultured, DMER64, Treponema, and Hydrogenispora, as well as the archaea genera Methanosarcina, RumEn_M2, Bathyarchaeia, and Methanomassiliicocus, dominated the microbial community with a high methane yield. This study is the first to demonstrate the microbial community structure involved in the AD of Sargassum spp. The pretreatments presented in this study can help overcome the limitations associated with methane yield.

Adjuvant Topical Interferon Alpha 2b for the Treatment of Monkeypox Ocular Manifestations.

PURPOSE: The aim of this study was to report a case of ocular Mpox that responded favorably to treatment with topical interferon and oral doxycycline. METHODS: This is a case report of a previously healthy 24-year-old woman who developed a pustular rash, headache, fever, arthralgia, sore throat, and asthenia 3 weeks before attending to our clinic. Her main complaint at the moment of the visit was pain, photophobia, foreign body sensation, blurred vision, red eye, and discharge on the left eye. The slit-lamp examination of the left eye showed severe conjunctival hyperemia associated with tarsal follicles, 360 degrees ciliary injection, diffuse corneal epithelial edema with white linear epithelial infiltrates, pigmented and nonpigmented keratic precipitates, and two 1-mm peripheral corneal ulcers with white infiltrates, associated with positive fluorescein staining. Anterior chamber cellularity and flare were mildly present. RESULTS: Mpox with ocular manifestations diagnosis was confirmed by real-time quantitative reverse transcription polymerase chain reaction assay (qRT-PCR) testing; samples were taken from corneal, conjunctival, and nasopharynx swab as well as a skin scab. Topical interferon alpha 2b 1 MIU/mL every 6 hours for 1 month and oral doxycycline 100 mg BID were administered along with other medications with consequent decrease of inflammation and malaise symptoms 1 week later, associated with uncorrected visual acuity improvement. CONCLUSIONS: Alternative and efficacious treatment options for Mpox ocular manifestations are needed to prevent further disease progression and sequelae in countries with no access to the gold-standard therapy. Topical interferon alpha 2b and oral doxycycline have shown adequate response as shown with this patient.

Visual impairment associated with diabetic retinopathy and macular edema: a hospital-based study.

BACKGROUND: Data on visual impairment (VI) in patients with diabetes are necessary in order to guide economic and human resources for reducing its prevalence. OBJECTIVE: To estimate the prevalence of diabetic retinopathy-related VI in patients with type 2 diabetes in a hospital-based setting. MATERIAL AND METHODS: Cross-sectional study carried out from 2014 to 2019 in an ophthalmology outpatient clinic. Any VI was defined as corrected pin-hole visual acuity in the better eye of ≥ 0.24 logMAR. The presence of diabetic retinopathy (DR), diabetic macular edema (DME) and cataract was evaluated. RESULTS: A total of 840 patients were included; median diabetes duration was 15 years. The prevalence of VI was 30%. DR was found in 62% of patients (30% had sight-threatening DR [STDR]), 17% had referable DME, and 3%, cataracts. The odds ratio for moderate or worse VI was 9.02 for STDR (p < 0.001), 5.89 for referable DME (p = 0.001), and 2.51 for cataract (p = 0.006). CONCLUSION: Thirty percent of participants had some degree of VI. Moderate or worse VI showed a strong association with STDR and referable DME.

ANTECEDENTES: Los datos sobre discapacidad visual (DV) en pacientes con diabetes son necesarios para orientar los recursos económicos y humanos que disminuyan su prevalencia. OBJETIVO: Estimar la prevalencia de DV relacionada con retinopatía diabética en pacientes con diabetes tipo 2 en un entorno hospitalario. MATERIAL Y MÉTODOS: Estudio transversal realizado de 2014 a 2019 en una consulta externa de oftalmología. Cualquier DV se definió como agudeza visual corregida con agujero estenopeico en el ojo con mejor visión (≥ 0.24 logMAR). Se evaluó la presencia de retinopatía diabética, edema macular diabético (EMD) y cataratas. RESULTADOS: Se incluyeron 840 pacientes; la mediana de duración de la diabetes fue de 15 años. La prevalencia de DV fue de 30 %. Se encontró retinopatía diabética en 62 % (30 % tenía retinopatía diabética que amenazaba la visión [RDAV]); 17 %, EMD y 3 %, cataratas. La razón de momios para DV moderada o de mayor gravedad fue de 9.02 para RDAV (p < 0.001), 5.89 para EMD referible (p = 0.001) y 2.51 para catarata (p = 0.006). CONCLUSIÓN: Treinta por ciento de los participantes tenía algún grado de DV. La DV moderada o de mayor gravedad mostró una fuerte asociación con RDAV y EMD referible.

Discapacidad visual asociada a retinopatía diabética y edema macular: un estudio de base hospitalaria / Visual impairment associated with diabetic retinopathy and macular edema: a hospital-based study

Resumen Antecedentes: Los datos sobre discapacidad visual (DV) en pacientes con diabetes son necesarios para orientar los recursos económicos y humanos que disminuyan su prevalencia. Objetivo: Estimar la prevalencia de DV relacionada con retinopatía diabética en pacientes con diabetes tipo 2 en un entorno hospitalario. Material y métodos: Estudio transversal realizado de 2014 a 2019 en una consulta externa de oftalmología. Cualquier DV se definió como agudeza visual corregida con agujero estenopeico en el ojo con mejor visión (≥ 0.24 logMAR). Se evaluó la presencia de retinopatía diabética, edema macular diabético (EMD) y cataratas. Resultados: Se incluyeron 840 pacientes; la mediana de duración de la diabetes fue de 15 años. La prevalencia de DV fue de 30 %. Se encontró retinopatía diabética en 62 % (30 % tenía retinopatía diabética que amenazaba la visión [RDAV]); 17 %, EMD y 3 %, cataratas. La razón de momios para DV moderada o de mayor gravedad fue de 9.02 para RDAV (p < 0.001), 5.89 para EMD referible (p = 0.001) y 2.51 para catarata (p = 0.006). Conclusión: Treinta por ciento de los participantes tenía algún grado de DV. La DV moderada o de mayor gravedad mostró una fuerte asociación con RDAV y EMD referible.

Abstract Background: Data on visual impairment (VI) in patients with diabetes are necessary in order to guide economic and human resources for reducing its prevalence. Objective: To estimate the prevalence of diabetic retinopathy-related VI in patients with type 2 diabetes in a hospital-based setting. Material and methods: Cross-sectional study carried out from 2014 to 2019 in an ophthalmology outpatient clinic. Any VI was defined as corrected pin-hole visual acuity in the better eye of ≥ 0.24 logMAR. The presence of diabetic retinopathy (DR), diabetic macular edema (DME) and cataract was evaluated. Results: A total of 840 patients were included; median diabetes duration was 15 years. The prevalence of VI was 30 %. DR was found in 62 % of patients (30 % had sight-threatening DR [STDR]), 17 % had referable DME, and 3 %, cataracts. The odds ratio for moderate or worse VI was 9.02 for STDR (p < 0.001), 5.89 for referable DME (p = 0.001), and 2.51 for cataract (p = 0.006). Conclusion: Thirty percent of participants had some degree of VI. Moderate or worse VI showed a strong association with STDR and referable DME.

Don't Miss Me: Midfoot Sprains, A Point-of-Care Review.

Athletes practicing high-contact sports are exposed to an increased risk of midfoot injuries, namely midtarsal sprains. The complexity of reaching an accurate diagnosis is clearly depicted in the reported incidence of midtarsal sprains, ranging from 5% to 33% of ankle inversion injuries. Because the focus of the treating physician and physical therapist is on lateral stabilizing structures, midtarsal sprains are missed at initial evaluation in up to 41% of patients, with delayed treatment as a result.Detecting acute midtarsal sprains requires a high degree of clinical awareness. Radiologists must become familiar with the characteristic imaging findings of normal and pathologic midfoot anatomy to avoid adverse outcomes such as pain and instability. In this article we describe Chopart joint anatomy, mechanisms of midtarsal sprains, clinical importance, and key imaging findings with a focus on magnetic resonance imaging. A team effort is essential to provide optimal care for the injured athlete.