Selective Modulation of the Keratoconic Stromal Microenvironment by FSH and LH.

Keratoconus (KC) affects the corneal structure, with thinning and bulging outward into a conelike shape. Irregular astigmatism and decreased visual acuity appear during puberty and progress into the mid-30s, with unpredictable disease severity. The cause of KC is recognized as multifactorial, but remains poorly understood. Hormone imbalances are a significant modulator of the onset of KC. This study sought to investigate the role of gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in KC, using a three-dimensional, self-assembled matrix in vitro model. Healthy corneal fibroblasts and human KC cells in the corneal stroma were isolated, cultured, and stimulated with stable vitamin C to promote extracellular matrix assembly. Cultures were further stimulated with 2.5 or 10 mIU/mL FSH and 5 or 35 mIU/mL LH. Samples were evaluated for cell proliferation and morphology via BrdU assay and imaging; protein expression was assessed via Western blot analysis. Proliferation was significantly greater in human KC cells compared to healthy corneal fibroblasts with LH stimulation, but no changes were found with FSH stimulation. Additionally, in sex hormone receptors, fibrotic markers, proteoglycans, and members of the gonadotropin signaling pathway were significantly changed, largely driven by exogenous LH. The impact of exogenous FSH/LH in the KC stromal microenvironment was demonstrated. These results highlight the need to further examine the role of FSH/LH in KC and in human corneal homeostasis.

Liquid biopsy-based circulating tumour (ct)DNA analysis of a spectrum of myeloid and lymphoid malignancies yields clinically actionable results.

AIMS: Liquid biopsy (LBx)-based next-generation sequencing (NGS) of circulating tumour DNA (ctDNA) can facilitate molecular profiling of haematopoietic neoplasms (HNs), particularly when tissue-based NGS is infeasible. METHODS AND RESULTS: We studied HN LBx samples tested with FoundationOne Liquid CDx, FoundationOne Liquid, or FoundationACT between July 2016 and March 2022. We identified 271 samples: 89 non-Hodgkin lymphoma (NHL), 43 plasma-cell neoplasm (PCN), 41 histiocytoses, 27 myelodysplastic syndrome (MDS), 25 diffuse large B-cell lymphoma (DLBCL), 22 myeloproliferative neoplasm (MPN), 14 Hodgkin lymphoma (HL), and 10 acute myeloid leukaemia (AML). Among 73.4% with detectable pathogenic alterations, median maximum somatic allele frequency (MSAF) was 16.6%, with AML (36.2%), MDS (19.7%), and MPN (44.5%) having higher MSAFs than DLBCL (3.9%), NHL (8.4%), HL (1.5%), PCN (2.8%), and histiocytoses (1.8%) (P = 0.001). LBx detected characteristic alterations across HNs, including in TP53, KRAS, MYD88, and BTK in NHLs; TP53, KRAS, NRAS, and BRAF in PCNs; IGH in DLBCL; TP53, ATM, and PDCD1LG2 in HL; BRAF and MAP2K1 in histiocytoses; TP53, SF3B1, DNMT3A, TET2, and ASXL1 in MDS; JAK2 in MPNs; and FLT3, IDH2, and NPM1 in AML. Among 24 samples, the positive percent agreement by LBx was 75.7% for variants present in paired buffy coat, marrow, or tissues. Also, 75.0% of pairs exhibited alterations only present on LBx. These were predominantly subclonal (clonal fraction of 3.8%), reflecting the analytical sensitivity of LBx. CONCLUSION: These data demonstrate that LBx can detect relevant genomic alterations across HNs, including at low clonal fractions, suggesting a potential clinical utility for identifying residual or emerging therapy-resistant clones that may be undetectable in site-specific tissue biopsies.

Temperature-dependent dielectric relaxations and transport properties of Sm3+ & La3+ doped Bi-oxide nanoparticles.

The suggested novel rare-earth doped bismuth calcium cobaltites Bi2Ca2-2xSmxLaxCoO6 (x = 0.000-0.075) were synthesized by a co-precipitation route. XRD was utilized for structural information. SEM and EDX were used for microstructural and elemental analysis. AC conductivities (σac) were measured at temperatures of 100-500 °C. The σac of all synthesized samples increased as the temperature increased, indicating that they are semi-conductive. The conduction process of all the synthesized samples was examined using Jonscher's power law. The spreading factor and relaxation time of all the synthesized samples were studied using nonlinear Debye fitting. At a high temperature of 500 °C, the dielectric curve showed anomalous behaviour that was related to the negative values of the dielectric constant at 500 kHz-3 MHz. The studied (Sm-La)-doped samples showed higher values of the dielectric constant (1.03 × 108). The Cole-Cole plot used in the impedance investigation reveals that as the temperature rises, the diameter of the arcs decreases, implying a drop in impedance and rises in conductivity. The growing trend of DC electrical conductivity with temperature depicts the semi-conductive nature of the synthesized materials.

Current trends in the management of corneal neovascularization.

PURPOSE OF REVIEW: The aim of this study was to highlight recent developments in the medical and surgical management of corneal neovascularization (NV). RECENT FINDINGS: Improved understanding and diagnostic criteria among clinicians have led to advancements in the characterization of corneal NV and objective assessment of treatment response through ancillary imaging devices. Developments in corneal NV treatments, such as antivascular endothelial growth factor, fine needle diathermy, and photodynamic therapy, have improved treatment success rates and visual outcomes. More recent surgical treatment advancements include corneal cross-linking, endothelial keratoplasty, and mitomycin intravascular chemoembolization. Finally, a greater appreciation of the molecular pathogenesis and angiogenic factors involved in corneal NV has identified numerous potential targeted therapies in the future. SUMMARY: The management of corneal NV has evolved to include several standalone and combination medical and surgical options. Additionally, improvements in quantifying corneal NV and understanding its molecular basis have contributed to new management strategies with improved outcomes.

DIAGNOSTIC PATTERNS OF AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To characterize prevalence estimates by race, age, sex, and comorbidity (diabetes and hypertension) within the Medicare beneficiary demographic. METHODS: In this US population-based retrospective cohort analysis, the Vision and Eye Health Surveillance System was analyzed for a 100% sample of Medicare Fee-For-Service beneficiary populations of Asians and non-Hispanic Whites between 2014 and 2018. Exclusionary criteria included beneficiaries younger than 40 years. Prevalence rate ratios, defined as prevalence rate for Asians divided by prevalence rate for non-Hispanic Whites, were calculated using multivariate negative binomial regression or Pearson-scaled Poisson regression, stratified by age, sex, and comorbidity. RESULTS: A total of 21,892,200 Medicare beneficiaries fulfilled the inclusionary criteria in 2018. Of the entire cohort, 3.2% of the beneficiaries (N = 714,500) were Asian. For beneficiaries aged 40 to 64 years, Asian male (prevalence rate ratios 1.73, 95% confidence interval 1.64-1.83, P < 0.0001) and female (prevalence rate ratios 1.34, 95% confidence interval 1.28-1.41, P < 0.0001) beneficiaries had an increased prevalence rate of all age-related macular degeneration relative to non-Hispanic Whites. Significant time-wise increases in prevalence rate ratios were observed within several age groups, sexes, and comorbidities (race-time interaction coefficients P < 0.05 ). CONCLUSION: This analysis highlights increased age-related macular degeneration prevalence estimates within the Asian American demographic relative to non-Hispanic Whites. Furthermore, specific Asian subpopulations are experiencing accelerated prevalence rates over time.

Optic Nerve Sheath Meningiomas: A National Surveillance, Epidemiology, and End Results (SEER) Database Analysis.

BACKGROUND: Optic nerve sheath meningioma (ONSM) is a rare optic nerve cancer with considerable morbidity. This national analysis validates previously known ONSM concepts while providing insight into novel risk factors. METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program was queried from 2000 to 2019 for all histologic subtypes of meningioma primary to the optic nerve. Relevant clinical and demographic variables were analyzed. Asymptotic one-sample test for binomial proportions and Cox proportional hazards modeling evaluated the significance of factor associations. RESULTS: A total of 51 ONSM cases were extracted. A greater proportion of cases were observed in females (N = 37, 73% , P < 0.001) and individuals with age 50 years or more (N = 29, 57% , P < 0.001); the mean number of months from diagnosis to treatment was 4.6 months (SD 4.1, range 13). Psychosocial epidemiologic parameter analysis demonstrated a greater proportion of patients with married status on diagnosis (N = 31, 61% , P < 0.001), listed total family income between $55,000 and $74,999 (N = 24, 47% , P < 0.001). Relative to cases diagnosed clinically only, cases diagnosed radiologically without microscopic confirmation experienced decreased all-cause mortality (HR = 0.041, P = 0.050). CONCLUSIONS: Our SEER national analysis affirms previously characterized ONSM concepts. Upon ONSM diagnosis and if needed, treatment protocols are not significantly delayed. Novel psychosocial factors for ONSM were identified, including marital status, total family income, and non-Hispanic white race. Additional ONSM diagnostics may reduce longitudinal mortality burden.

Type I interferon receptor signalling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice.

SARS-CoV-2 is a newly emerged coronavirus, causing the global pandemic of respiratory coronavirus disease (COVID-19). The type I interferon (IFN) pathway is of particular importance for anti-viral defense and recent studies identified that type I IFNs drive early inflammatory responses to SARS-CoV-2. Here, we use a mouse model of SARS-CoV-2 infection, facilitating viral entry by intranasal recombinant Adeno-Associated Virus (rAAV) transduction of hACE2 in wildtype (WT) and type I IFN receptor-1 deficient (Ifnar1-/- ) mice, to study the role of type I IFN signalling and innate immune responses during SARS-CoV-2 infection. Our data show that type I IFN signalling is essential for inducing anti-viral effector responses to SARS-CoV-2, control of virus replication, and to prevent enhanced disease. Furthermore, hACE2-Ifnar1-/- mice had increased gene expression of the chemokine Cxcl1 and airway infiltration of neutrophils as well as reduced and delayed production of monocyte-recruiting chemokine CCL2. hACE2-Ifnar1-/- mice showed altered recruitment of inflammatory myeloid cells to the lung upon SARS-CoV-2 infection, with a shift from Ly6C+ to Ly6C- expressing cells. Together, our findings suggest that type I IFN signalling deficiency results in a dysregulated innate immune response to SARS-CoV-2 infection.

Dry eye in the upper blepharoplasty patient: a study comparing orbicularis-sparing versus orbicularis-excising techniques.

PURPOSE: To compare subjective and objective dry eye syndrome (DES) metrics preoperatively and postoperatively in patients undergoing bilateral upper eyelid blepharoplasty (ULB) using orbicularis-sparing versus orbicularis-excising techniques. METHODS: A double-blind, randomized clinical trial was conducted on patients without prior DES or other severe conditions who presented to our institution between 2017 and 2019 for routine functional ULB. Patients were randomized into two treatment arms: bilateral ULB using the orbicularis-sparing technique or bilateral ULB using the orbicularis-excising technique. One subjective and seven objective DES assessments were performed on all patients preoperatively and 1 month and 1 year after surgery. RESULTS: A total of 63 patients were recruited for the study. Standard Patient Evaluation of Eye Dryness (SPEED) scores decreased in both treatment groups at 1 month and 1 year postoperatively. This change did not significantly vary based on surgical technique. Objective DES assessments were not significantly changed at both postoperative time points for either group. There was a correlation between the severity of preoperative DES symptoms and the subjective improvement of DES symptoms postoperatively in both groups. CONCLUSIONS: ULB with an orbicularis-sparing or orbicularis-excising technique does not worsen subjective or objective DES metrics and so, surgeons may confidently use either surgical technique. These findings may impact postoperative expectations for surgeons and patients alike.

Critical role of pathology and laboratory medicine in the conversation surrounding access to healthcare.

Pathology and laboratory medicine are a key component of a patient's healthcare. From academic care centres, community hospitals, to clinics across the country, pathology data are a crucial component of patient care. But for much of the modern era, pathology and laboratory medicine have been absent from health policy conversations. Though select members in the field have advocated for an enhanced presence of these specialists in policy conversations, little work has been done to thoroughly evaluate the moral and ethical obligations of the pathologist and the role they play in healthcare justice and access to care. In order to make any substantive improvements in access to care, pathology and laboratory medicine must have a seat at the table. Specifically, pathologists and laboratorians can assist in bringing about change through improving clinician test choice, continuing laboratory improvement programmes, promoting just advanced diagnostic distribution, triage testing and be good stewards of healthcare dollars, and recruiting a more robust laboratory workforce. In order to get to that point, much work has to be done in pathology education and the laboratory personnel training pipeline but there also needs to be adjustments at the system level to better involve this invaluable group of specialists in these policy conversations.

Phenotypic clues that predict underlying cytogenetic/genetic abnormalities in myeloid malignancies: A contemporary review.

Precise subclassification of myeloid malignancies per the World Health Organization (WHO) classification system and the International Consensus Classification of Myeloid Neoplasms and Acute Leukaemias (ICC) requires investigation and documentation of the presence of cytogenetic and/or molecular genetic changes. These ancillary studies not only help in diagnosis, but also the prognosis of disease; however, they take time to be completed. In contrast, morphological evaluation of material from the blood and bone marrow specimens of cases where myeloid malignancies are suspected is usually completed quickly. Cytomorphological assessment may predict genetic changes and can be helpful in triaging acuity. This is especially true in haematological emergencies such as acute promyelocytic leukaemia (APL), where prompt APL-specific therapy can be life changing. Similarly, some morphological clues may help identify core binding factor leukaemias where a diagnosis of acute myeloid leukaemia (AML) could be rendered without reaching the 20% blast cutoff with immediate treatment-decision implications, or even a subset of cases of AML with FLT3 ITD/NPM1 mutation(s) which show characteristic features. Even though FISH/cytogenetics and/or PCR are still required for establishing the final diagnosis, evaluation for the presence of specific cytomorphological features that help predict genetic changes can be a useful tool to help guide early therapy.

Exploring the anthelmintic activity of Olea europaea L (Olive) leaves extract and oleuropein in mice naturally infected with Aspiculuris tetraptera.

Oxyuriasis, caused by the nematode Enterobius vermicularis, is one of the cosmopolitan intestinal infections of humans. Aspiculuris tetraptera commonly infects mice and it is morphologically similar to E. vermicularis. Parasitic resistance reduces the efficiency of synthetic drugs and poses economic impacts on the dairy sector, thus necessitating novel anthelmintic agents. Olea europaea L. (Olive) is a bioactive plant with potent pharmacological activities. However, its effects on oxyurids are poorly known, and no studies are currently exploring olives' anthelmintic potential. In this study, we investigated the pharmacokinetic behaviors of O. europaea leaves extract (OLE) and its phenolic compound oleuropein in mice infected with A. tetraptera, in comparison with Albendazole (ABZ), a standard drug used to treat parasitic worms. Fecal flotation method was used to identify the infestation with A. tetraptera eggs by examining the stool samples from mice. Infected animals were divided into 7 groups. 250 mg/kg, 500 mg/kg, and 1000 mg/kg doses of OLE, 5 mg/kg and 20 mg/kg doses of oleuropein, 10 mg/kg of ABZ and tap water were orally administered by gavage for 7 days during treatments. Drug efficacies and statistical differences between the treatments and controls were evaluated. Our results revealed 92.43 % efficacy of ABZ, similar to 92.19 % efficacy of 1000 mg/kg of OLE. At the same time, 250 mg/kg and 500 mg/kg concentrations of OLE remained 70.03 % and 63.18 % effective in reducing worm counts. Efficacy percentages of 5 mg/kg and 20 mg/kg of oleuropein were 9.27 % and 70.56 %, respectively. Statistical analysis of ABZ was significant compared to 1000 mg/kg of OLE, which was almost equal but insignificant. In general, our results confirm the anthelmintic potential of OLE and oleuropein against mice pinworms and open the way for targeted extraction of bioactive compounds from plants to optimize its use in human and veterinary medicine.

Lung directed antibody gene transfer confers protection against SARS-CoV-2 infection.

BACKGROUND: The COVID-19 pandemic continues to be a worldwide threat and effective antiviral drugs and vaccines are being developed in a joint global effort. However, some elderly and immune-compromised populations are unable to raise an effective immune response against traditional vaccines. AIMS: We hypothesised that passive immunity engineered by the in vivo expression of anti-SARS-CoV-2 monoclonal antibodies (mAbs), an approach termed vectored-immunoprophylaxis (VIP), could offer sustained protection against COVID-19 in all populations irrespective of their immune status or age. METHODS: We developed three key reagents to evaluate VIP for SARS-CoV-2: (i) we engineered standard laboratory mice to express human ACE2 via rAAV9 in vivo gene transfer, to allow in vivo assessment of SARS-CoV-2 infection, (ii) to simplify in vivo challenge studies, we generated SARS-CoV-2 Spike protein pseudotyped lentiviral vectors as a simple mimic of authentic SARS-CoV-2 that could be used under standard laboratory containment conditions and (iii) we developed in vivo gene transfer vectors to express anti-SARS-CoV-2 mAbs. CONCLUSIONS: A single intranasal dose of rAAV9 or rSIV.F/HN vectors expressing anti-SARS-CoV-2 mAbs significantly reduced SARS-CoV-2 mimic infection in the lower respiratory tract of hACE2-expressing mice. If translated, the VIP approach could potentially offer a highly effective, long-term protection against COVID-19 for highly vulnerable populations; especially immune-deficient/senescent individuals, who fail to respond to conventional SARS-CoV-2 vaccines. The in vivo expression of multiple anti-SARS-CoV-2 mAbs could enhance protection and prevent rapid mutational escape.

Revealing the presence of tear extracellular vesicles in Keratoconus.

Extracellular vesicles (EVs) are lipid-bound vesicles that originate from the endosomal system or budded off from the plasma membrane. EVs are involved in cell-cell communication via transporting DNA, RNA, and proteins from one cell to another. Tear EVs (tEVs) have been reported in dry eye, SjÓ§gren's Syndrome, and primary open-angle glaucoma. In this study, we sought to investigate the presence of tEVs in relation to keratoconus (KC). Tears were passively collected from the lateral meniscus from 10 healthy (5 males and 5 females) and 9 KC (4 males and 5 females) subjects. Tear samples were processed and analyzed using the ExoView™ R100. Statistical analysis was performed using a Mann-Whitney U non-parametric Student's t-test. All tEVs, in both Healthy and KC subjects, showed a CD9+ dominant tEV cohort independent of sex. A significant decrease in CD63+/CD9+ and CD63+/CD81+/CD9+ was found in the male KC tEVs (p < 0.05), but not in females compared to their healthy counterparts. Neither Healthy nor KC tEVs showed differences in the total number of tEVs, however significant differences were identified between the sexes (p < 0.05), with males having a higher number of tEVs. tEVs diameters ranged from 50 to 200 nm, in both Healthy and KC cohorts, with the majority in the 50-80 nm range suggesting exosome-dominant cohorts. To our knowledge, this is the first time, to date, that tEVs have been isolated and characterized in KCs. While further studies are warranted, the tEVs differences between KC and Healthy subjects suggest a potential role for tEVs in KC pathogenesis.

Toward a More Just System of Care in Molecular Pathology.

Policy Points American health care policy must be critically assessed to establish the role it plays in sustaining and alleviating the health disparities that currently exist in molecular genetic testing. It is critical to understand the economic and sociocultural influences that drive patients to undergo or forgo molecular testing, especially in marginalized patient populations. A multipronged solution with actions necessary from multiple stakeholders is required to reduce the cost of health care, rebalance regional disparities, encourage physician engagement, reduce data bias, and earn patients' trust. CONTEXT: The health status of a population is greatly influenced by both biological processes and external factors. For years, minority and low socioeconomic patient populations have faced worse outcomes and poorer health in the United States. Experts have worked extensively to understand the issues and find solutions to alleviate this disproportionate burden of disease. As a result, there have been some improvements and successes, but wide gaps still exist. Diagnostic molecular genetic testing and so-called personalized medicine are just now being integrated into the current American health care system. The way in which these tests are integrated can either exacerbate or reduce health disparities. METHODS: We provide case scenarios-loosely based on real-life patients-so that nonexperts can see the impacts of complex policy decisions and unintentional biases in technology without needing to understand all the intricacies. We use data to explain these findings from an extensive literature search examining both peer-reviewed and gray literature. FINDINGS: Access to diagnostic molecular genetic testing is not equitable or sufficient, owing to at least five major factors: (1) cost to the patient, (2) location, (3) lack of provider buy-in, (4) data-set bias, and (5) lack of public trust. CONCLUSIONS: Molecular genetic pathology can be made more equitable with the concerted efforts of multiple stakeholders. Confronting the five major factors identified here may help us usher in a new era of precision medicine without its discriminatory counterpart.

A Case of Primary Myelofibrosis With Transformation to Leukemia Cutis.

ABSTRACT: We report an extraordinary case of primary myelofibrosis with transformation to leukemia cutis. A 64-year-old Caucasian man with a history of JAK2-positive primary myelofibrosis presented with erythematous papulonodules on his right lower extremity. A punch biopsy revealed a normal epidermis with an underlying diffuse dermal infiltrate composed of medium-to-large-sized myeloid cells and leukocytes. Neoplastic cells were immunoreactive for LCA, CD34, CD61, CD117, and CD68 and negative for lysozyme, CD20, CD3, myeloperoxidase, and TdT. These findings were consistent with a diagnosis of leukemia cutis. A concurrent bone marrow biopsy demonstrated a markedly fibrotic, hypercellular marrow without a significant increase in blasts. With no morphologic evidence of bone marrow involvement by acute myeloid leukemia, our case suggests that the patient's primary myelofibrosis transformed to leukemia cutis. Our patient died 2 months after the onset of his skin nodules. Our case demonstrates that leukemia cutis should be included in the differential diagnosis for cutaneous nodular lesions in patients with a history of an advanced-stage hematological malignancy.

Frugal Method of Notch Modification of Scleral Contact Lenses in the Setting of Complex Ocular Surface Anatomy.

ABSTRACT: Scleral contact lenses (ScCLs) have gained popularity as a treatment of refractive errors in patients with complex anterior segment pathology. Patients with mechanical abnormalities of the ocular surface may be unsuccessful with traditional ScCL fitting. Scleral contact lens modifications, such as notching and microvaulting, typically incur additional financial costs and require the services of professional laboratories. We describe a frugal method of ScCL notch modification that can be performed by a practitioner using readily available tools in a single office visit. Two patients with abnormal ocular surface anatomy were fit with the practitioner-modified ScCL and achieved successful visual rehabilitation. We offer this method as a potentially economical and effective technique to achieve successful ScCL fitting in this challenging patient population with pathologies that may preclude standard ScCL usage.

Hyperparameter Optimization of Bayesian Neural Network Using Bayesian Optimization and Intelligent Feature Engineering for Load Forecasting.

This paper proposes a new hybrid framework for short-term load forecasting (STLF) by combining the Feature Engineering (FE) and Bayesian Optimization (BO) algorithms with a Bayesian Neural Network (BNN). The FE module comprises feature selection and extraction phases. Firstly, by merging the Random Forest (RaF) and Relief-F (ReF) algorithms, we developed a hybrid feature selector based on grey correlation analysis (GCA) to eliminate feature redundancy. Secondly, a radial basis Kernel function and principal component analysis (KPCA) are integrated into the feature-extraction module for dimensional reduction. Thirdly, the Bayesian Optimization (BO) algorithm is used to fine-tune the control parameters of a BNN and provides more accurate results by avoiding the optimal local trapping. The proposed FE-BNN-BO framework works in such a way to ensure stability, convergence, and accuracy. The proposed FE-BNN-BO model is tested on the hourly load data obtained from the PJM, USA, electricity market. In addition, the simulation results are also compared with other benchmark models such as Bi-Level, long short-term memory (LSTM), an accurate and fast convergence-based ANN (ANN-AFC), and a mutual-information-based ANN (ANN-MI). The results show that the proposed model has significantly improved the accuracy with a fast convergence rate and reduced the mean absolute percent error (MAPE).

Unravelling Novel Roles of Salivary Exosomes in the Regulation of Human Corneal Stromal Cell Migration and Wound Healing.

Salivary exosomes have demonstrated vast therapeutic and diagnostic potential in numerous diseases. This study pioneers previously unexplored roles of SE in the context of corneal wound healing by utilizing primary corneal stromal cells from healthy (HCFs), type I diabetes mellitus (T1DMs), type II DM (T2DMs), and keratoconus (HKCs) subjects. Purified, healthy human SEs carrying tetraspanins CD9+, CD63+, and CD81+ were utilized. Scratch and cell migration assays were performed after 0, 6, 12, 24, and 48 h following SE stimulation (5 and 25 µg/mL). Significantly slower wound closure was observed at 6 and 12 h in HCFs with 5 µg/mL SE and T1DMs with 5 and 25 µg/mL SE. All wounds were closed by 24-hour, post-wounding. HKCs, T1DMs, and T2DMs with 25µg/mL SE exhibited a significant upregulation of cleaved vimentin compared to controls. Thrombospondin 1 was significantly upregulated in HCFs, HKCs, and T2DMs with 25 µg/mL SE. Lastly, HKCs, T1DMs, and T2DMs exhibited a significant downregulation of fibronectin with 25 µg/mL SE. Whether SEs can be utilized to clinical settings in restoring corneal defects is unknown. This is the first-ever study exploring the role of SEs in corneal wound healing. While the sample size was small, results are highly novel and provide a strong foundation for future studies.

The Role of Estriol and Estrone in Keratoconic Stromal Sex Hormone Receptors.

Keratoconus (KC) is a progressive corneal thinning disease that manifests in puberty and worsens during pregnancy. KC onset and progression are attributed to diverse factors that include: environmental, genetics, and hormonal imbalances; however, the pathobiology remains elusive. This study aims to determine the role of corneal stroma sex hormone receptors in KC and their interplay with estrone (E1) and estriol (E3) using our established 3D in vitro model. Healthy cornea stromal cells (HCFs) and KC cornea stromal cells (HKCs), both male and female, were stimulated with various concentrations of E1 and E3. Significant changes were observed between cell types, as well as between males and females in the sex hormone receptors tested; androgen receptor (AR), progesterone receptor (PR), estrogen receptor alpha (ERα), and estrogen receptor beta (ERß) using Western blot analysis. E1 and E3 stimulations in HCF females showed AR, PR, and ERß were significantly upregulated compared to HCF males. In contrast, ERα and ERß had significantly higher expression in HKC's females than HKC's males. Our data suggest that the human cornea is a sex-dependent, hormone-responsive tissue that is significantly influenced by E1 and E3. Therefore, it is plausible that E1, E3, and sex hormone receptors are involved in the KC pathobiology, warranting further investigation.

Update on Biometry and Lens Calculation - A Review of the Basic Principles and New Developments. / Update Biometrie und Linsenberechnung ­ ein Review zu Grundlagen und neuen Entwicklungen.

These days, accurate calculation of artificial lenses is an important aspect of patient management. In addition to the classic theoretical optical formulae there are a number of new approaches, most of which are available as online calculators. This review aims to explain the background of artificial lens calculation and provide an update on study results based on the latest calculation approaches. Today, optical biometry provides the computational basis for theoretical optical formulae, ray tracing, and also empirical approaches using artificial intelligence. Manufacturer information on IOL design and IOL power recorded as part of quality control could improve calculations, especially for higher IOL powers. With modern measurement data, there is further potential for improvement in the determination of the axial length to the retinal pigment epithelium and by adopting a sum-of-segment approach. With the available data, the cornea can be assumed to be a thick lens. The Kane formula, the EVO 2.0 formula, the Castrop formula, the PEARL-DGS, formula and the OKULIX calculation software provide consistently good results for artificial lens calculations. Excellent refractive results can be achieved using these tools, with approximately 80% having an absolute prediction error within 0.50 dpt, at least in highly selected study populations. The Barrett Universal II formula also produces excellent results in the normal and long axial length range. For eyes with short axial lengths, the use of Barrett Universal II should be reconsidered; in this case, one of the methods mentioned above is preferable. Second Eye Refinement can also be considered in this patient population, in conjunction with established classic third generation formulae.