Search

Human clinical isolates of the Mycobacterium avium complex, from hospitals in Bogotá, were studied using a wide range of molecular tests including PCR restriction-enzyme analysis (PRA) of the hsp65 gene. Up to 21 of the isolates were identified as M. avium PRA variant III (Mav III), a variant obtained only from isolates on the American continent. In contrast to previous reports, restriction fragment length polymorphism analysis using IS 1245 and IS 1311 showed a single copy for each insertion sequence (IS) in the majority (19/21) of the Colombian Mav III isolates under study. In order to analyse whether the ISs were inserted in a relevant genomic region, experimental conditions were established to determine the insertion loci of each single copy of both ISs in the genome. Analysis of genomic insertion loci indicated that both IS 1245 and IS 1311 were present in areas containing putatively truncated integrases and/or transposases, which may have an influence on the mobility of the inserted IS. In addition, a conserved genomic region was identified for the insertion of IS 1311; this region could be part of the IS 1311 itself. [ABSTRACT FROM AUTHOR]

In vitro studies have suggested that proteoglycans facilitate signaling by mammalian growth factors, but genetic evidence supporting this role has been lacking. Here, we characterize the ENU-induced mutation lazy mesoderm (lzme), which disrupts the single mouse gene encoding UDP-glucose dehydrogenase (Ugdh), an enzyme required for the synthesis of the glycosaminoglycan (GAG) side chains of proteoglycans. lzme mutants arrest during gastrulation with defects in migration of mesoderm and endoderm, a phenotype similar to that of mutants in the fibroblast growth factor (Fgf) pathway. Analysis of the expression of molecular markers indicates that Fgf signaling is blocked in lzme mutant embryos. In contrast, signaling by the growth factors Nodal and Wnt3, which are also essential during mouse gastrulation, appears to be normal in lzme embryos. The results demonstrate that proteoglycans are required during mouse gastrulation specifically to promote Fgf signaling. [Copyright &y& Elsevier]

Simple Summary: BRCA2 is an essential gene for DNA repair by homologous recombination and is often mutated in families at risk of breast and ovarian cancer. In this study we identified CDK5RAP3 tumor suppressor as a new BRCA2-interacting protein. CDK5RAP3 negatively regulates DNA repair of double-strand breaks, providing a new mechanism of DNA damage resistance. Consistently, gene expression data analysis showed CDK5RAP3 overexpression in breast cancer is associated with poorer survival. Finally, we identified common genetic variations in the CDK5RAP3 locus as potentially associated with breast and ovarian cancer risk in a large cohort of BRCA1 and BRCA2 mutation carriers. BRCA2 is essential for homologous recombination DNA repair. BRCA2 mutations lead to genome instability and increased risk of breast and ovarian cancer. Similarly, mutations in BRCA2-interacting proteins are also known to modulate sensitivity to DNA damage agents and are established cancer risk factors. Here we identify the tumor suppressor CDK5RAP3 as a novel BRCA2 helical domain-interacting protein. CDK5RAP3 depletion induced DNA damage resistance, homologous recombination and single-strand annealing upregulation, and reduced spontaneous and DNA damage-induced genomic instability, suggesting that CDK5RAP3 negatively regulates double-strand break repair in the S-phase. Consistent with this cellular phenotype, analysis of transcriptomic data revealed an association between low CDK5RAP3 tumor expression and poor survival of breast cancer patients. Finally, we identified common genetic variations in the CDK5RAP3 locus as potentially associated with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Our results uncover CDK5RAP3 as a critical player in DNA repair and breast cancer outcomes. [ABSTRACT FROM AUTHOR]

Neuropathic dry eye is one of the most frequently seen complications after corneal refractive surgery, however, its incidence decreases in a significant manner along the first six months postoperative, reaching between 10 and 45% incidence. However, little is known on the inflammatory status of the ocular surface during this recovery process. We aim to analyze the clinical and tear molecule concentration changes along six months after advanced surface ablation for myopia correction, in a prospective study including 18 eyes of 18 subjects who bilaterally underwent advanced surface ablation corneal refractive surgery. Clinical variables (uncorrected distance visual acuity, symptoms, conjunctival hyperemia, tear osmolarity, tear stability, corneal fluorescein staining, conjunctival lissamine staining, Schirmer test, and corneal esthesiometry) and a panel of 23 pro and anti-inflammatory cytokines/chemokines concentration in tears preoperatively and at 1, 3 and 6 months postoperatively were evaluated. We found that uncorrected distance visual acuity improved significantly from baseline at 1-month visit, symptoms improved and tear osmolarity decreased significantly from baseline at 3-month visit and there was a decrease in mechanical corneal threshold between 1-month and 3- and 6-month visits. Regarding tear molecules, IL-4, IL-5, IL-6, IL-13, IL-17A, and IFN-γ tear levels were significantly increased at all the three visits, compared to preoperative levels at V0; IL-2 and VEGF were also significantly increased at 1-month and 6-month visits, but not at 3-month visit, whereas IL-9 IL-10 and IL-12 were only significantly increased at 6-month visit. Although we found that there is a recovery in clinical variables at 6 months postoperatively (i.e. neuropathic dry eye was not developed in the sample), ocular surface homeostasis is not completely restored, as it can be seen by the changes in concentration of some pro and anti-inflammatory molecules measured in tears. • Clinical variables completely restore after 6 months of ASA refractive surgery. • Some tear pro-inflammatory cytokines/chemokines do not recover their basal values. • Ocular surface homeostasis is not completely restored after 6 months of ASA surgery. [ABSTRACT FROM AUTHOR]

The aims of this work were (a) to select the minimum concentrations of two bacteriocin‐producing lactobacilli strains to reduce Listeria monocytogenes growth in whole milk, (b) to evaluate the individual and combined application of these chosen lactobacilli concentrations as protective culture in this food and, (c) to estimate if lactobacilli growth caused undesirable changes in the visible characteristics of milk. The selected minimum lactobacilli concentration with antilisterial activity was 106 CFU ml−1 for both lactobacilli. Although a high initial concentration of L. monocytogenes (104 CFU ml−1) was added to milk, a notable reduction on listerial counts (2–4 log CFU ml−1) was achieved in comparison to the control. These lactobacilli showed a good adaptability in milk reaching optimal counts and not causing undesirable visible changes. In conclusion, the use of these lactobacilli could be considered as a bio‐strategy potentially effective to limit the contamination by L. monocytogenes in certain milk‐derived products. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the short-term efficacy of cyclosporine A (CsA)-0.1% cationic emulsion (CE) in patients with dry eye disease (DED) and mitigation of the inflammatory flares triggered by desiccating stress environments. Methods: A single-center non-randomized clinical trial was performed at a tertiary care setting. Twenty patients with DED treated with CsA 0.1% CE were exposed to a normal controlled environment (NCE) (23 °C, 50% relative humidity) and an adverse controlled environment (ACE) (23 °C, 10% relative humidity, 0.43 m/s localized airflow) during baseline and the 1- and 3-month visits. Patients underwent the following evaluations: conjunctival hyperemia and staining, corneal fluorescein staining (CFS) using the Oxford and Cornea and Contact Lens Research Unit (CCLRU) scale, meibomian gland (MG) secretion quality, Dry Eye Questionnaire-5, Symptom Assessment in Dry Eye (SANDE II), and Change in Dry Eye Symptoms Questionnaire. Multivariate models were adjusted for statistical analysis. Results: Nineteen women and one man (mean age, 58.9 ± 12.3 years) completed the study. All symptom questionnaires, CFS, conjunctival hyperemia and staining, and MG secretion quality improved (p ≤ 0.003) with 1 month of treatment; improvements were maintained after 3 months (p ≤ 0.02), except for SANDE II (p ≥ 0.07). The CFS worsening (total CCLRU) after baseline ACE exposure (from 8.6 to 10.1) was higher, although not significant (p = 0.64), compared with 1 month (from 5.4 to 5.8) and 3 months (from 5.0 to 5.9) after treatment. Conclusion: Topical CsA-0.1% CE improved DED signs and symptoms after 1 month of treatment under controlled environmental conditions. Future studies should confirm the benefit of CsA-0.1% CE in desiccating stress environments. Trial Registration: ClinicalTrials.gov identifier, NCT04492878. [ABSTRACT FROM AUTHOR]

Purpose To assess the efficacy of topical 0.1% fluorometholone in dry eye disease (DED) patients for ameliorating the worsening of the ocular surface when exposed to adverse environments. Design Single-center, double-masked, randomized, vehicle-controlled clinical trial. Participants Forty-one patients showing moderate to severe DED. Methods Patients randomly received 1 drop 4 times daily of either topical 0.1% fluorometholone (FML group) or topical polyvinyl alcohol (PA group) for 22 days. Corneal and conjunctival staining, conjunctival hyperemia, tear film breakup time (TBUT), tear osmolarity, and the Symptom Assessment in Dry Eye (SANDE) questionnaire scores were determined at baseline. Variables were reassessed on day 21 before and after undergoing a 2-hour controlled adverse environment exposure and again on day 22. Main Outcomes Measures Percentage of patients showing an increase 1 point or more in corneal staining and a reduction of 2 points or more (0–10 scale) in SANDE score, after the controlled adverse environment exposure and 24 hours later. Results After 21 days of treatment, the FML group showed greater improvements in corneal and conjunctival staining, hyperemia, and TBUT than the PA group ( P ≤0.03). After the adverse exposure, the percentage of patients having a 1-grade or more increase in corneal staining was significantly ( P = 0.03) higher in the PA group (63.1% vs. 23.8%, respectively). Additionally, the FML group showed no significant changes in corneal staining (mean, 0.86; 95% confidence interval [CI], 0.47–1.25; vs. mean, 1.05; 95% CI, 0.59–1.51, for visit 2 and 3, respectively), conjunctival staining (mean, 0.95; 95% CI, 0.54–1.37 vs. mean, 1.19; 95% CI, 0.75–1.63), and hyperemia (mean, 0.71; 95% CI, 0.41–1.02 vs. 1.14; 95% CI, 0.71–1.58) after the exposure, whereas for the PA group, there was significant worsening ( P ≤0.009) in these variables (corneal staining: mean, 1.95; 95% CI, 1.57–2.33 vs. mean, 2.58; 95% CI, 2.17–2.98; conjunctival staining: mean, 1.68; 95% CI, 1.29–2.08 vs. mean, 2.47; 95% CI, 2.07–2.88; hyperemia: mean, 1.95; 95% CI, 1.63–2.26 vs. mean, 2.84; 95% CI, 2.62–3.07). Conclusions Three-week topical 0.1% fluorometholone therapy is effective not only in reducing ocular surface signs in DED patients, but also especially in preventing exacerbation caused by exposure to a desiccating stress. [ABSTRACT FROM AUTHOR]

To assess the prophylactic effect of LipiFlow treatment in Meibomian gland dysfunction (MGD) patients exposed to an adverse environmental humidity. MGD patients were exposed to normal (23 °C; 50% relative humidity; 30 min) and adverse (23 °C; 10% relative humidity; 2 h) controlled environments consecutively during baseline and follow-up visits (3, 6, and 12 months) after a single LipiFlow treatment. Ocular Surface Disease Index (OSDI), lipid layer thickness (LLT), fluorescein tear break-up time (TBUT), corneal and conjunctival staining, change in dry eye symptoms questionnaire (CDES-Q), and Meibomian gland yielding liquid secretion (MGYLS), were assessed. Linear mixed-effects and cumulative logit mixed models were fitted to assess the effect of the LipiFlow treatment over time and within the controlled environments. Seventeen females and 4 males (59.6 ± 9.4 years) completed the study. LLT and TBUT did not vary significantly (p > 0.05) after LipiFlow treatment. OSDI, corneal and conjunctival staining, and MGYLS scores were improved (p ≤ 0.01) 12 months after treatment. After the adverse exposure, corneal staining increased at all visits (p = 0.01), and there was no significant improvement in CDES-Q scores after LipiFlow treatment (p ≥ 0.07). One LipiFlow treatment improved objective and subjective outcomes in MGD disease for at least one year. Further studies are needed to support that LipiFlow might also help as an adjuvant to avoid acute flares against an adverse environmental humidity. [ABSTRACT FROM AUTHOR]

Aims: Potassium (K+) and iron (Fe) deficiency impeded plant growth and development. Because of the increase in soil salinization, plant challenged with nutrient availability were arisen. Thus, understanding the effect of salinity on the mechanisms involved in macro and microelement uptake is crucial.Two kinds of experiments were used to study the interactive effect of salinity with K+ or Fe deficiency. In the first one, Cakile maritima was subjected to the treatments for a longer period while in the second one, C. maritima and Arabidopsis thaliana were subjected to similar treatments but for a shorter period.Long-term responses to salinity and their interaction with K+ or Fe deficiency reduced shoot and root growth, chlorophyll content, generated an imbalance in nutrient status. Both deficiencies increased root ethylene production. A stimulation of root ferric chelate reductase (FCR) activity was only recorded in Fe deficient plants. Salinity increased Na+ concentration notably in shoots, disturbed plant nutrient homeostasis, inhibited root hair proliferation and abolished the induction of FCR activity and ethylene synthesis either by K+ or Fe shortage. Similar results were obtained in C. maritima and A. thaliana once treatments were imposed during a shorter period with the halophyte being more tolerant. In A. thaliana, the mechanisms involved in K+ and Fe uptake were inhibited by high salinity.Salinity inhibited the induction of several physiological and biochemical responses either by K+ or Fe deficiency by abolishing the main mechanisms involved in the uptake of both elements.Methods: Potassium (K+) and iron (Fe) deficiency impeded plant growth and development. Because of the increase in soil salinization, plant challenged with nutrient availability were arisen. Thus, understanding the effect of salinity on the mechanisms involved in macro and microelement uptake is crucial.Two kinds of experiments were used to study the interactive effect of salinity with K+ or Fe deficiency. In the first one, Cakile maritima was subjected to the treatments for a longer period while in the second one, C. maritima and Arabidopsis thaliana were subjected to similar treatments but for a shorter period.Long-term responses to salinity and their interaction with K+ or Fe deficiency reduced shoot and root growth, chlorophyll content, generated an imbalance in nutrient status. Both deficiencies increased root ethylene production. A stimulation of root ferric chelate reductase (FCR) activity was only recorded in Fe deficient plants. Salinity increased Na+ concentration notably in shoots, disturbed plant nutrient homeostasis, inhibited root hair proliferation and abolished the induction of FCR activity and ethylene synthesis either by K+ or Fe shortage. Similar results were obtained in C. maritima and A. thaliana once treatments were imposed during a shorter period with the halophyte being more tolerant. In A. thaliana, the mechanisms involved in K+ and Fe uptake were inhibited by high salinity.Salinity inhibited the induction of several physiological and biochemical responses either by K+ or Fe deficiency by abolishing the main mechanisms involved in the uptake of both elements.Results: Potassium (K+) and iron (Fe) deficiency impeded plant growth and development. Because of the increase in soil salinization, plant challenged with nutrient availability were arisen. Thus, understanding the effect of salinity on the mechanisms involved in macro and microelement uptake is crucial.Two kinds of experiments were used to study the interactive effect of salinity with K+ or Fe deficiency. In the first one, Cakile maritima was subjected to the treatments for a longer period while in the second one, C. maritima and Arabidopsis thaliana were subjected to similar treatments but for a shorter period.Long-term responses to salinity and their interaction with K+ or Fe deficiency reduced shoot and root growth, chlorophyll content, generated an imbalance in nutrient status. Both deficiencies increased root ethylene production. A stimulation of root ferric chelate reductase (FCR) activity was only recorded in Fe deficient plants. Salinity increased Na+ concentration notably in shoots, disturbed plant nutrient homeostasis, inhibited root hair proliferation and abolished the induction of FCR activity and ethylene synthesis either by K+ or Fe shortage. Similar results were obtained in C. maritima and A. thaliana once treatments were imposed during a shorter period with the halophyte being more tolerant. In A. thaliana, the mechanisms involved in K+ and Fe uptake were inhibited by high salinity.Salinity inhibited the induction of several physiological and biochemical responses either by K+ or Fe deficiency by abolishing the main mechanisms involved in the uptake of both elements.Conclusion: Potassium (K+) and iron (Fe) deficiency impeded plant growth and development. Because of the increase in soil salinization, plant challenged with nutrient availability were arisen. Thus, understanding the effect of salinity on the mechanisms involved in macro and microelement uptake is crucial.Two kinds of experiments were used to study the interactive effect of salinity with K+ or Fe deficiency. In the first one, Cakile maritima was subjected to the treatments for a longer period while in the second one, C. maritima and Arabidopsis thaliana were subjected to similar treatments but for a shorter period.Long-term responses to salinity and their interaction with K+ or Fe deficiency reduced shoot and root growth, chlorophyll content, generated an imbalance in nutrient status. Both deficiencies increased root ethylene production. A stimulation of root ferric chelate reductase (FCR) activity was only recorded in Fe deficient plants. Salinity increased Na+ concentration notably in shoots, disturbed plant nutrient homeostasis, inhibited root hair proliferation and abolished the induction of FCR activity and ethylene synthesis either by K+ or Fe shortage. Similar results were obtained in C. maritima and A. thaliana once treatments were imposed during a shorter period with the halophyte being more tolerant. In A. thaliana, the mechanisms involved in K+ and Fe uptake were inhibited by high salinity.Salinity inhibited the induction of several physiological and biochemical responses either by K+ or Fe deficiency by abolishing the main mechanisms involved in the uptake of both elements. [ABSTRACT FROM AUTHOR]

Dry eye (DED) is a prevalent disease with immune-mediated inflammation as the principal pathophysiological etiology. Olive pomace, the major by-product of the olive oil industry, is rich in high-value polyphenols. Their anti-inflammatory and immunomodulatory activities were determined on human CD4+ T cells (hTCD4+) and in a DED animal model. The viability of hTCD4+ cells isolated from peripheral blood and activated with phytohemagglutinin-M was evaluated after treatment for 48 h with an olive pomace extract (OPT3, 0.10–0.40 mg/mL) and its major compound, hydroxytyrosol (25–100 μM). Regarding the DED animal model, 100 μM hydroxytyrosol, 0.20 mg/mL OPT3, or vehicle (borate buffer) were topically administered to 14 days-desiccating stress-exposed (constant airflow/scopolamine administration) C57BL/6 mice. Tear volume, corneal fluorescein staining (CFS), CD4+, and CD8+ T cell count in lymph nodes (flow cytometry), and IP-10 and TNF-α gene expression (qRT-PCR) in the cornea, conjunctiva, and lacrimal glands were evaluated. OPT3 (0.2–0.4 mg/mL) and hydroxytyrosol (100 μM) significantly reduced hTCD4+ proliferation. In mice, both treatments reduced lacrimal gland IP-10 gene expression. OPT3 also decreased CFS, and conjunctival IP-10 and corneal TNF-α gene expression. In lymph nodes, hydroxytyrosol reduced CD3+, OPT3, and CD8+ count. Thus, a high-value application as a promising DED protection was proposed for olive pomace. [ABSTRACT FROM AUTHOR]

Mucosal chemokines have antimicrobial properties and play an important role in mucosal immunity. However, little is known about their expression on the ocular surface. This study aimed to analyze the expression of the mucosal chemokines CCL28, CXCL14 and CXCL17 in corneal and conjunctival epithelial cells under in vitro dry eye (DE) conditions, and in conjunctival samples from healthy subjects and DE patients. Human corneal epithelial cells (HCE) and immortalized human conjunctival epithelial cells (IM-HConEpiC) were incubated under hyperosmolar (400–500 mOsM) or inflammatory (TNF-α 25 ng/mL) conditions for 6 h and 24 h to measure CCL28 , CXCL14 , and CXCL17 gene expression by RT-PCR and their secretion by immunobead-based analysis (CCL28, CXCL14) and ELISA (CXCL17). Additionally, twenty-seven DE patients and 13 healthy subjects were included in this study. DE-related questionnaires (OSDI, mSIDEQ and NRS) evaluated symptomatology. Ocular surface integrity was assessed using vital staining. Tactile sensitivity was measured with Cochet-Bonnet esthesiometer, and mechanic and thermal (heat and cold) sensitivity using Belmonte's non-contact esthesiometer. Subbasal nerve plexus and dendritic cell density were analyzed by in vivo confocal microscopy. Conjunctival cells from participants were collected by impression cytology to measure mucosal chemokines gene expression by RT-PCR. Our results showed that HCE and IM-HConEpiC cells increased CCL28, CXCL14, and CXCL17 secretion under hyperosmolar conditions. The gene expression of CCL28 was significantly upregulated in conjunctival samples from DE patients. CCL28 expression correlated positively with symptomatology, corneal staining, heat sensitivity threshold, and dendritic cell density. CXCL14 expression correlated positively with age, ocular pain, conjunctival staining, tactile sensitivity, and image reflectivity. CXCL17 expression correlated positively with corneal staining. These results suggest that corneal and conjunctival epithelial cells could be a source of CCL28, CXCL14, and CXCL17 on the ocular surface and that CCL28 might be involved in DE pathogenesis. • Hyperosmolarity increases CCL28, CXCL14 and CXCL17 secretion in vitro. • First report on CCL28 , CXCL14 and CXCL17 gene expression in healthy human conjunctiva. • Dry eye patients have increased CCL28 gene expression in conjunctival cells. • CCL28 , CXCL14 and CXCL17 levels correlate with clinical severity in dry eye patients. [ABSTRACT FROM AUTHOR]

Purpose: To study whether some ocular surface alterations could be associated with contact lens (CL) wearers suffering from CL discomfort (CLD) detected using the Contact Lens Dry Eye Questionnaire (CLDEQ)-8.Methods: Forty-one soft CL wearers further classified into symptomatic CL wearers (SCLW) and asymptomatic CL wearers (ACLW) by the CLDEQ-8, and 20 non CL wearers (NCLW) were included. Tear osmolarity, slit-lamp biomicroscopy findings, tear film break-up time, corneal and conjunctival staining, and Schirmer test were performed 24 h after CL removal. Data were compared among groups using the analysis of variance and the Student t-test or the Kruskal-Wallis H and the Mann-Whitney U tests, applying the Bonferroni correction. Correlations between the CLDEQ-8 and the clinical signs were performed using the Spearman correlation coefficient.Results: Twenty-four SCLW, 17 ACLW and 20 NCLW were recruited. There were significant differences among groups for tear osmolarity (p < 0.001), limbal hyperaemia (p = 0.014), and tarsal hyperaemia (p = 0.031). Pairwise comparisons revealed that SCLW and ACLW had higher tear osmolarity (p < 0.003, both comparisons) and limbal hyperaemia (p = 0.027 and p = 0.048, respectively) than NCLW. Moreover, SCLW had higher tarsal hyperaemia (p = 0.030) than NCLW. No significant correlations were found (p > 0.05).Conclusion: The CLDEQ-8 was ineffective to detect clinical alterations between SCLW and ACLW; therefore, the use of questionnaires alone remains being the best approach to detect CLD. The role of the tarsal conjunctiva in the development of CLD should be analyzed in future studies. [ABSTRACT FROM AUTHOR]

This study aimed to assess the subjective and objective differences among the steps of the contact lens discomfort (CLD) progression classification established by the Tear Film & Ocular Surface Society (TFOS) using questionnaires and clinical signs, and to propose a simplified classification. Contact lens (CL) wearers were evaluated in a single visit. The Contact Lens Dry Eye Questionnaire (CLDEQ)-8, the Contact Lens Discomfort Index, and Visual Analog Scales for discomfort and dryness were administered. The non-invasive break-up time, the tear film lipid layer thickness, conjunctival hyperaemia and papillae, lid-parallel conjunctival folds, the fluorescein tear film break-up time, corneal and conjunctival staining, lid wiper epitheliopathy, and the Schirmer test were assessed. Sign and symptom scores were compared among TFOS CLD progression steps using analysis of variance or the Kruskal–Wallis H test. Steps 1 and 2 (reduced comfort), and steps 3 and 4 (reduced wearing time) of the TFOS classification were combined to obtain a simplified classification, and the same comparison was performed. A p-value ≤ 0.05 was considered statistically significant. One hundred-fifty CL wearers (97 women and 53 men) aged 34.4 ± 12.6 years were included. In the TFOS classification, there were significant differences between step 0 (no CLD) and the rest of the severity steps for the scores obtained in all questionnaires (p ≤ 0.015). All steps were differentiated (p ≤ 0.032) based on the simplified classification for all questionnaires, except steps 1 and 2 for the CLDEQ-8 and dryness VAS (p = 0.089 and p = 0.051, respectively). There were no differences (all p ≥ 0.06) between the sign scores among the steps of either classification. CLD management is encouraged from its first appearance. Simplifying the phases of CLD severity may allow a more accurate classification and a better awareness of the problem by clinicians and CL wearers by using more straightforward simple messages. [ABSTRACT FROM AUTHOR]

Aims/Purpose: To characterize the Meibomian gland (MG) morphology in healthy subjects with an automatic software. Methods: An automatic software was developed for image analysis in R code, consisting of 4 stages: (1) selection of the region of interest, (2) image preprocessing to obtain a binary and a skeleton image, (3) modelling of each MG to fit each MG to a piecewise linear model, and (4) quantification of the following MG features: tortuosity, MG shortening, number of MGs, deviation from a vertical line, and MG area. Meibography images of the upper eyelid were acquired using the Easy Tear View+®. A group of 156 healthy subjects were included, with a mean age and confidence interval (CI) of 43.88 (95% CI: 41.38–46.37) years, range 16–76 years. Reference intervals (RI) were calculated for each MG feature to be used as a diagnostic tool to classify a specific value as normal or non‐normal. Generalized Additive Models for Location, Scale and Shape were used to estimate the percentile curve for each morphologic feature of MG, considering the influence of age and sex. Results: Age had an influence on tortuosity, mean = 0.3 (95% CI: 0.3–0.31), RI: 0.19–0.4 <20 years, and 0.24–0.39 at 50–60 years. Age and sex had an influence in the MG shortening, mean = 63% (95% CI: 62–64%), mean RI: 58–74% <20 years; 59–84% >75 years; women RI: 56–71% <20 years; 57–82% >75 years. The rest of the variables were not affected by age or sex: number of MGs = 16.05 (95% CI: 15.28–16.82), RI: 8–27; vertical deviation = 0.37 (95% CI: 0.36–0.38), RI: 0.29–0.45, and MG area = 14% (95% CI: 14–15%), RI: 8.17–19.81%. Conclusions: Tortuosity variability decreases between 45 and 60 years of age. The MG shortening increases with age and is higher in men. These values could be useful to classify a meibography image as normal or non‐normal, helping to diagnose MG alterations in an objective way. [ABSTRACT FROM AUTHOR]

Only in very special circumstances can new beaches develop due to natural processes in areas where they did not exist before. One such circumstance is related to volcanic eruptions, when a lava flow reaches the ocean. The sudden formation of new beaches is examined in this paper. Following the Tajogaite volcano eruption in September 2021, two lava deltas formed after the arrival of several lava flows to the coast. Attached to the flanks and front of these lava deltas, thirteen gravel beaches formed in just a few months. Detailed topographic and sedimentologic information was collected both on the beaches and adjacent submarine areas. The volume of sediments accumulated on these beaches was obtained after comparison of the actual topography with a previous one, yielding a total net accumulation of about 79,000 m3 of volcanoclastic pebbles and cobbles. This material comes from two major source areas: extensive offshore deposits of volcanic clasts within the depth of closure which are moved onshore by low steepness swell waves, and rock fragments derived from erosion of the lava delta front by high energy waves. Two types of beaches were identified. Beaches that already existed prior to the eruption showed significant increases in cross-shore length and height, with a net accumulation of 67,000 m3. In contrast, the dismantling of the lava delta front led to the formation of totally new beaches in certain locations, accounting for about 12,000 m3 of sediments. Several features, such as a steep foreshore slope, a well-developed storm berm and the presence of wood debris in many of these beaches at several meters height and tens of meters inland, are examined conjointly with the sediment characteristics, showing how textural maturity can change in response to the forcing agents acting in the different parts of the beach profile. The future evolution of these beaches is also considered. This study can enrich the knowledge regarding how new gravel beaches can form in volcanic settings. • Two lava-deltas with thirteen new beaches formed after the Tajogaite eruption. • Cobble-sized sediments and steep beachface slopes are dominant. • Strong spatial changes in textural maturity across the beach. • Low-steepness and storm waves play a major role in beaches formation. • Major source areas are volcanoclastic submerged deposits and lava-deltas erosion. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether variations in multipurpose disinfecting solution (MPDS) storage osmolarity from inappropriate contact lens (CL) case cleaning affect ocular surface integrity and wearer comfort.Methods: There were twenty contact lens cases (study CLCs) in the study group. Ten were filled with ReNu Multiplus(®) and 10 with SoloCare Aqua™ (MPDS-1 and -2, respectively) and kept closed for 8h; the cases were then emptied and kept open for air-drying for 16h. This procedure was carried out every day for two months. Storage solution osmolarity was measured on days 0, 15, 30, 45 and 60. Ten subjects were then fitted with both month-old lenses stored in the study CLCs and with new lenses stored in new cases with fresh solution for 24h (control CLCs). Symptoms, tear osmolarity and percentage of subjects whose conjunctival hyperaemia and ocular surface staining scores changed were determined after 1h of wear.Results: Study CLC osmolarity increased in both solutions after two months (p<0.05). For MPDS-1 there were differences in stinging between study CLCs and control CLCs after 10min of CL wear (p=0.04), and in comfort after 10 (p=0.035) and 60min wear (p=0.042). Significant (p<0.05) differences between study CLC and control CLC groups were also found for MPDS-2 in limbal hyperaemia (study: 50% change; control: 0% change) and bulbar and corneal staining (study: 80% change; control: 20% change).Conclusion: The stored-MPDS osmolarity increase caused by air-drying the CLCs could affect the ocular surface. This increase might reduce lens wear comfort. [ABSTRACT FROM AUTHOR]

The impact of pre-fermentative cold soak, alone or in combination with dry ice addition, on colour, phenolic and volatile composition of Tempranillo wines at 12 months after bottling was studied. A control wine without cold soak was also evaluated. A sample set consisting of 66 wines was investigated. The results from ANOVA and PCA analysis showed significant treatment-related differences for a number of chemical measurements, as well as overlapping effects. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) of the data showed that the dry ice addition treatment had a major effect on the anthocyanin fraction and on the levels of ethyl decanoate, 2-phenylethyl acetate and decanoic acid. In comparison, the cold soak treatment only had a slight effect on the bisulphite bleaching anthocyanins and volatile composition. [ABSTRACT FROM AUTHOR]

Purpose: To examine the relationship between contact lens (CL) discomfort and meibomian gland (MG) morphology assessed by a semi-objective software in subjects without an alteration of MG function (meibum quality and expressibility).Methods: Nineteen symptomatic (CLDEQ-8 ≥ 12) CL wearers, 19 asymptomatic (CLDEQ-8 < 12) wearers, and 22 non-wearers were recruited. Upper and lower eyelid meibography images were taken and the following parameters were analysed using a semi-objective software in the central 2/3 of each eyelid: number of MG, number of partial MG, percentage of MG loss and percentage of tortuosity. One-way ANOVA or Kruskal-Wallis H test were used for comparisons among groups. The relationships between CLDEQ-8 and MG morphology parameters were analysed using the Spearman correlation coefficient and multivariable linear regression models.Results: No significant differences were found among groups in the MG morphology of the upper or lower eyelids. In all CL wearers, a significant correlation with CLDEQ-8 was found in the upper eyelid for the number of MG (rho = 0.47, p = 0.003). In symptomatic wearers, significant correlations with CLDEQ-8 were found in the lower eyelid for the number of partial MG (rho = 0.49, p = 0.03) and the percentage of partial MG (rho = 0.61, p = 0.005). In all CL wearers, multivariable models were fitted to explain CLDEQ-8 score including the number of MG, the number of partial MG and the percentage of MG loss from the lower eyelid (R2 = 0.19; p = 0.007), and the number of MG from the upper eyelid (R2 = 0.19; p = 0.001). In symptomatic wearers, a model was fitted including the percentage of MG loss from the lower eyelid (R2 = 0.30; p = 0.016).Conclusions: Alterations of MG morphology, without clinically apparent alteration of MG function, can be involved in causing CL discomfort and influence the degree of symptoms. The differences in findings between eyelids indicate the need to monitor both eyelids, especially the lower one, in CL wearers. [ABSTRACT FROM AUTHOR]

Purpose To study the relationship among the variables intensity of the end-of-day (EOD) dryness, corneal sensitivity and blink rate in soft contact lens (CL) wearers. Methods Thirty-eight soft CL wearers (25 women and 13 men; mean age 27.1 ± 7.2 years) were enrolled. EOD dryness was assessed using a scale of 0–5 (0, none to 5, very intense). Mechanical and thermal (heat and cold) sensitivity were measured using a Belmonte's gas esthesiometer. The blink rate was recorded using a video camera while subjects were wearing a hydrogel CL and watching a film for 90 min in a controlled environmental chamber. Results A significant inverse correlation was found between EOD dryness and mechanical sensitivity ( r : −0.39; p = 0.02); however, there were no significant correlations between EOD dryness and thermal sensitivity. A significant ( r : 0.56; p < 0.001) correlation also was observed between EOD dryness and blink rate, but no correlations were found between blink rate and mechanical or thermal sensitivity. Conclusions CL wearers with higher corneal sensitivity to mechanical stimulation reported more EOD dryness with habitual CL wear. Moreover, subjects reporting more EOD dryness had an increased blink rates during wear of a standard CL type. The increased blink rate could act to improve the ocular surface environment and relieve symptoms. [ABSTRACT FROM AUTHOR]

[Display omitted] The number of patients affected by Dry Eye Disease (DED) had notably increased worldwide, addressing the need of novel therapeutic approaches. Polyphenols, quercetin (QUE) and resveratrol (RSV) show necessary antioxidant and anti-inflammatory properties to manage DED, but their application as topical eyedrops is restricted by low aqueous solubility and low chemical stability. Cyclodextrins (CD) are widely used to improve physicochemical characteristics of drugs. Consequently, the aim of this study was to make a comparison between binary complexes with quercetin, resveratrol and cyclodextrins and tertiary complexes adding hyaluronic acid (HA). Both complexes were able to enhance solubility and stability of QUE and RSV. AFM imaging and DLS measurements disclose the formation of spherical nanoaggregates within tertiary complexes of both QUE and RSV with mean diameters of 103 and 82 nm. Neither complex demonstrated cytotoxic effect in in vitro studies in corneal (HCE) and conjunctival (IM-ConjEpi) cell lines. In HCE cells, complexes containing QUE or RSV at their highest concentrations were able to scavenge more than 95 % of the ROS that were produced intracellularly (p < 0.005). Similar response was observed with IM-ConjEpi cells. The antioxidant effect was maintained in the complexes with HA. This confirmed their potential as viable topical treatment for DED. [ABSTRACT FROM AUTHOR]

The purpose of this study was to analyze inflammation- and pain-related molecules in tears of patients suffering from chronic ocular pain associated with dry eye (DE) and/or a previous corneal refractive surgery (RS). Based on history, symptomatology, and clinical signs, the subjects (n = 180, 51.0 ± 14.7 years, 118 females, 62 males) in this cross-sectional study were assigned to one of five groups: DE and chronic ocular pain after RS (P/DE-RS, n = 52); asymptomatic subjects, i.e., without DE and chronic ocular pain, after RS (A-RS, n = 30); DE and chronic ocular pain without previous RS (P/DE-nonRS, n = 31); DE, no pain, and no previous RS (DE-nonRS, n = 35); and asymptomatic subjects with no previous RS (controls, n = 32). The tear concentrations of 20 cytokines and substance P (SP) were analyzed by immunobead-based assay and enzyme-linked immunosorbent assay, respectively. We found that tear levels of interleukin (IL)-10 and SP were increased in the RS groups. There were significant differences in IL-8/CXCL8 among the five groups. Nerve growth factor (NGF) tear levels were significantly higher in P/DE-RS than in DE-nonRS and controls. IL-9 had the highest percentage of detection in the P/DE-RS and P/DE-nonRS groups, while macrophage inflammatory protein (MIP)-1α, IL-2, and interferon (IFN)-γ were higher in the P/DE-RS, A-RS, and P/DE-nonRS groups. IL-17A was detected only in the A-RS group. Moderate correlations were observed in the A-RS, P/DE-nonRS, DE-nonRS and controls groups. A positive correlation was obtained between growth related oncogene concentration and tear break-up time (rho = 0.550; p = 0.012), while negative correlation was found between monocyte chemoattractant protein-3/CCL7 and conjunctival staining (rho = −0.560; p = 0.001), both in the A-RS group. IL-10 correlated positively with ocular pain intensity (rho = 0.513; p = 0.003) in the P/DE-nonRS group. Regulated on Activation Normal T Cell Expressed and Secreted/CCL5 correlated negatively with conjunctival staining (rho = −0.545; p = 0.001) in the DE-nonRS group. SP correlated negatively with corneal staining (rho = −0.559; p = 0.001) in the controls. In conclusion, chronic ocular pain was associated with higher IL-9 tear levels. IL-10, SP, MIP-1α/CCL3, IL-2, and IFN-γ were associated with previous RS. Higher levels of IL-8/CXCL8, MIP-1α/CCL3, IL-2, and IFN-γ were associated with DE-related inflammation, while NGF levels were related to chronic ocular pain and DE in RS patients. These findings suggest that improved knowledge of tear cytokines and neuromodulators will lead to a more nuanced understanding of how these molecules can serve as biomarkers of chronic ocular pain, leading to better therapeutic and disease management decisions. • Inflammation- and pain-related molecules in patients with ocular pain and dry eye. • Cytokines and neuromodulators in tears differ in subjects with chronic ocular pain. • Molecular differences in tears related to dry eye inflammation. • Different molecular profile associated with previous corneal refractive surgery. [ABSTRACT FROM AUTHOR]

Abstract: Hypercholesterolemia and low testosterone concentrations in men are associated with a high risk factor for atherosclerosis. It is known that cholesterol serves as the major precursor for the synthesis of the sex hormones. The bioactive peptides of the renin–angiotensin-system localized in the gonads play a key role in the relation between cholesterol and testosterone by modulating steroidogenesis and inhibiting testosterone production. In the present work, we evaluated the effects of diet-induced hypercholesterolemia on circulating testosterone levels and its relationship with the testicular RAS-regulating specific aminopeptidase activities in male mouse. A significant decrease in serum circulating levels of testosterone was observed after induced hypercholesterolemia. The changes found in aminopeptidase activities suggest a role of Ang III and Ang IV in the regulation of steroidogenesis. [Copyright &y& Elsevier]

In this work, the surface of porous titanium samples obtained by the space-holder technique was treated with a femtosecond laser to improve their osseointegration. Instrumented micro-indentation and scratch test were implemented to evaluate the tribo-mechanical behavior of the surface of the modified samples. A detailed study of micro-hardness, stiffness, scratch resistance and elastic recovery was performed. Also, in vitro analysis was carried out to evaluate the cellular behavior. Modified samples showed less ALP activity, which could indicate a greater differentiation of the cells. The cell culture was similar in all cases although more differentiated morphology, good cell adherence and biological response were observed on treated samples. Finally, the discs with a pore size between 100–200 μm present being potential candidates for the replacement of small portions of damaged cortical bone tissues. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: To assess morphological changes in the meibomian glands (MGs) pre- and post-hematopoietic stem cell transplantation (HSCT)., Methods: Participants yet to undergo HSCT were included in a pre-HSCT group. Meibography images of both lids were graded using Pult's meiboscale and analyzed using a semi-automatic software program. Meibography variables in the pre-HSCT group were compared with those in a control group of healthy participants. The follow-up group, a subset of the pre-HSCT group, comprised participants followed up for at least 6 months post-HSCT. Ocular Surface Disease Index (OSDI), tear break-up time, corneal fluorescein staining, and Schirmer test were performed. The differences in meibography variables and ocular surface tests pre- and post-HSCT were analyzed., Results: Pre-HSCT and control groups comprised 181 and 24 participants, respectively. The pre-HSCT group had a higher meiboscale in the lower lid (2 vs. 1, p = 0.011) than controls. The follow-up group comprised 20 patients followed up for 12.75 months post-HSCT. After HSCT, the meiboscale of the upper lid was higher (2 vs. 1, p = 0.011), the MG area was lower in both lids (upper lid = 16.14% vs. 21.49%, p = 0.001; lower lid = 11.92% vs. 17.59%, p = 0.011), and the OSDI increased (15.2 vs. 26.85, p = 0.018) in the second visit compared to the first visit., Conclusions: Alterations in meibography were observed in patients pre- and post-HSCT. This may be attributed to the effect of treatments administered pre-HSCT, although an additive effect of conditioning regimen in the long-term cannot be discarded., Competing Interests: Declaration of Competing Interest None., (Copyright © 2025. Published by Elsevier Inc.)

BACKGROUNDDespite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma (HGSC) survive 10 or more years after standard treatment.METHODSWe evaluated the tumor microenvironment of this exceptional, understudied group using a large international cohort enriched for long-term survivors (LTS; 10+ years; n = 374) compared with mid-term (MTS; 5-7.99 years; n = 433) and short-term survivors (STS; 2-4.99 years; n = 416). Primary tumor samples were immunostained and scored for intraepithelial and intrastromal densities of 10 immune-cell subsets (including T cells, B cells, plasma cells, myeloid cells, PD-1+ cells, and PD-L1+ cells) and epithelial content.RESULTSPositive associations with LTS compared with STS were seen for 9 of 10 immune-cell subsets. In particular, the combination of intraepithelial CD8+ T cells and intrastromal B cells showed near 5-fold increased odds of LTS compared with STS. All of these associations were stronger in tumors with high epithelial content and/or the C4/Differentiated molecular subtype, despite immune-cell densities generally being higher in tumors with low epithelial content and/or the C2/Immunoreactive molecular subtype.CONCLUSIONThe tumor microenvironment of HGSC LTS is distinguished by the intersection of T and B cell coinfiltration, high epithelial content, and C4/differentiated molecular subtype, features which may inspire new approaches to immunotherapy.FUNDINGOvarian Cancer Research Program (OCRP) of the Congressionally Directed Medical Research Program (CDMRP), U.S. Department of Defense (DOD); American Cancer Society; BC Cancer Foundation; Canada's Networks of Centres of Excellence; Canadian Cancer Society; Canadian Institutes of Health Research; Cancer Councils of New South Wales, Victoria, Queensland, South Australia, and Tasmania, Cancer Foundation of Western Australia; Cancer Institute NSW; Cancer Research UK; Deutsche Forschungsgesellschaft; ELAN Funds of the University of Erlangen-Nuremberg; Fred C. and Katherine B. Andersen Foundation; Genome BC; German Cancer Research Center; German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research; Instituto de Salud Carlos III; Mayo Foundation; Minnesota Ovarian Cancer Alliance; Ministerio de Economía y Competitividad; Medical Research Council (MRC); National Center for Advancing Translational Sciences; National Health and Medical Research Council of Australia (NHMRC); Ovarian Cancer Australia; Peter MacCallum Foundation; Sydney West Translational Cancer Research Centre; Terry Fox Research Institute; The Eve Appeal (The Oak Foundation); UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; University of Pittsburgh School of Medicine; U.S. National Cancer Institute of the National Institutes of Health; VGH & UBC Hospital Foundation; Victorian Cancer Agency.

Objectives: To evaluate the reliability and agreement of tear meniscus height (TMH) measurements performed with a corneal analyzer and optical coherence tomography (OCT) technology in contact lens (CL) wearers and its correlation with contact lens discomfort symptoms., Methods: Asymptomatic and symptomatic CL wearers classified through the Contact Lens Dry Eye Questionnaire-8 were evaluated with the Corneal Analyzer (Topcon CA-800) and OCT technology (Topcon 3D OCT-2000). The repeatability and intraclass correlation coefficient (ICC) were calculated. The agreement between devices was calculated using the Bland-Altman method. The relationship between TMH measurements and the Contact Lens Dry Eye Questionnaire-8 and Contact Lens Discomfort Index scores was assessed through the Spearman correlation coefficient., Results: Seventy-nine asymptomatic and 42 symptomatic CL wearers aged 34.24±12.50 years were enrolled. The repeatability values obtained for the CA-800 were 0.07 mm in all cases, and the ICC was 0.93 for the whole sample. The CA-800 provided significantly ( P <0.01) higher TMH values than the OCT for the whole sample (0.22±0.08 vs. 0.17±0.06 mm). A weak indirect correlation (ρ=-0.22) between the OCT TMH measurement and Contact Lens Discomfort Index scores was found ( P ≤0.04)., Conclusion: The CA-800 provides reliable TMH measurements during CL wear; however, they might not be interchangeable with OCT ones. Tear meniscus height measurements might be useful as a complementary sign to detect CL discomfort, but it cannot be used alone as a diagnostic tool., Competing Interests: L. Valencia-Nieto is currently receiving a Grant FPU19/01109 from the Ministry of Universities and European Social Fund. Funders had no role in the study. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Contact Lens Association of Ophthalmologists.)

Updating the mosquito fauna occurring in a specific area is crucial, given that certain species serve as vectors capable of transmitting zoonotic arboviruses. This scientific note presents the first records of mosquitoes of the tribe Orthopodomyiini in the Yucatan Peninsula. Immature mosquitoes were collected on 2 occasions inside a large tree hole in Felipe Carrillo Puerto, Quintana Roo, Mexico. Thirteen adult specimens, reared from the immatures, were obtained and identified as Orthopodomyia kummi based on external characteristics of females and males. This species has been recorded in Panama, Costa Rica, El Salvador, Guatemala, Mexico, and marginally in the United States, but its presence in the Yucatan Peninsula had gone unnoticed until now. The knowledge about mosquitoes of the genus Orthopodomyia is limited, and their epidemiological importance remains uncertain. Therefore, further studies could provide insights into the ecological and infection dynamics associated with this species., (Copyright © 2024 by The American Mosquito Control Association, Inc.)

Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10 -8 ). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC., (© 2024. The Author(s).)