A Rare Devastating Complication of Lasik: Bilateral Fungal Keratitis

Purpose. To report an unusual case of severe bilateral fungal keratitis following laser in situ keratomileusis (LASIK). Method. A 48-year-old man developed bilateral diffuse corneal infiltration two weeks after LASIK. The corneal scrapings revealed fungal filaments but cultures were negative. Results. The corneal ulceration was improved on the left eye whereas spontaneous perforation occurred and finally evisceration was needed on the right eye despite topical and systemic antifungal treatment. Conclusions. Fungal keratitis, especially with bilateral involvement, is a very rare and serious complication of LASIK surgery. Clinical suspicion is crucial because most of fungal keratitis are misdiagnosed as bacterial keratitis and can lead serious visual results, even eye loss

International Undiagnosed Diseases Programs (UDPs): components and outcomes

Over the last 15 years, Undiagnosed Diseases Programs have emerged to address the significant number of individuals with suspected but undiagnosed rare genetic diseases, integrating research and clinical care to optimize diagnostic outcomes. This narrative review summarizes the published literature surrounding Undiagnosed Diseases Programs worldwide, including thirteen studies that evaluate outcomes and two commentary papers. Commonalities in the diagnostic and research process of Undiagnosed Diseases Programs are explored through an appraisal of available literature. This exploration allowed for an assessment of the strengths and limitations of each of the six common steps, namely enrollment, comprehensive clinical phenotyping, research diagnostics, data sharing and matchmaking, results, and follow-up. Current literature highlights the potential utility of Undiagnosed Diseases Programs in research diagnostics. Since participants have often had extensive previous genetic studies, research pipelines allow for diagnostic approaches beyond exome or whole genome sequencing, through reanalysis using research-grade bioinformatics tools and multi-omics technologies. The overall diagnostic yield is presented by study, since different selection criteria at enrollment and reporting processes make comparisons challenging and not particularly informative. Nonetheless, diagnostic yield in an undiagnosed cohort reflects the potential of an Undiagnosed Diseases Program. Further comparisons and exploration of the outcomes of Undiagnosed Diseases Programs worldwide will allow for the development and improvement of the diagnostic and research process and in turn improve the value and utility of an Undiagnosed Diseases Program

Effects of honey addition on antioxidative properties of different herbal teas

Tea and herbal infusions are among the major contributors of phenolic compounds, specifically flavonoids, in our daily diet. Honey is another antioxidant-rich food that is widely used as a natural sweetener. In this work, the effects of honey addition on antioxidant properties of different herbal teas were investigated. For this purpose, 2 different types of honey (flower and pine honey) were added into 9 different herbal teas (melissa, green tea, rosehip, sage, echinacea, fennel, linden, daisy, and ginger) at 4 different temperatures (55°C, 65°C, 75°C, and 85°C), and the changes in the content of total pheolics, total flavonoids, and total antioxidant capacity were determined. The total phenolic content and the total antioxidant capacity of the honey-added-tea samples were found to be increased (up to 57% for both), especially with pine honey and at higher temperatures of honey addition. The findings of this study supported the use of honey as a natural sweetener in tea in order to be able to benefit from the health-enhancing antioxidative properties of these two promising food products

A temporal approach for morphological indices of the common sole (Solea solea Linnaeus 1758) from the coast of the Aegean Sea, Turkey

810-818Temporal changes of the morphological indices (Relative Gut Length (RGL), Fullness Index (FI), Hepatosomatic Index (HSI), Visceral Index (VSI), Gonadosomatic Index (GSI) and Fulton condition)) in 122 (♀: 94, ♂: 19, immature: 9) common sole were evaluated. Total length-weight relationships were calculated as W = 0.085TL3.01 and W = 0.0547TL2.40 in females and males, respectively, whereby isometric growth was observed in females and negative allometric growth was observed in males. While there was no statistically significant difference was observed between the FI, HSI, Viscerosomatic Index (VSI), RGL and GSI values of both sexes, however, there was a statistically significant difference in terms of Fulton K values (P < 0.05). In addition, there are statistical differences between the sexes total lengths and the values of RGL, FI, HSI, VSI, and Fulton-K (P < 0.05), as it is discernible in their HSI and VSI index values according to the month the specimens were obtained (P < 0.05). According to the results of the analysis, it has been determined that the female common sole along the Aegean coast adjust their energy temporally and store the energy they obtain from vegetative and carnivorous feeding. Contrary to the situation seen in females, the male individuals invest in energy through omnivorous feeding, according to the diet in the active process. Based on the results, it can be stated that the VSI and HSI are both important indicators of fish condition status. The results found here may be useful in both fishery research and fishery management

A temporal approach for morphological indices of the common sole (Solea solea Linnaeus 1758) from the coast of the Aegean Sea, Turkey

Temporal changes of the morphological indices (Relative Gut Length (RGL), Fullness Index (FI), Hepatosomatic Index (HSI), Visceral Index (VSI), Gonadosomatic Index (GSI) and Fulton condition)) in 122 (♀: 94, ♂: 19, immature: 9) common sole were evaluated. Total length-weight relationships were calculated as W = 0.085TL3.01 and W = 0.0547TL2.40 in females and males, respectively, whereby isometric growth was observed in females and negative allometric growth was observed in males. While there was no statistically significant difference was observed between the FI, HSI, Viscerosomatic Index (VSI), RGL and GSI values of both sexes, however, there was a statistically significant difference in terms of Fulton K values (P &lt; 0.05). In addition, there are statistical differences between the sexes total lengths and the values of RGL, FI, HSI, VSI, and Fulton-K (P &lt; 0.05), as it is discernible in their HSI and VSI index values according to the month the specimens were obtained (P &lt; 0.05). According to the results of the analysis, it has been determined that the female common sole along the Aegean coast adjust their energy temporally and store the energy they obtain from vegetative and carnivorous feeding. Contrary to the situation seen in females, the male individuals invest in energy through omnivorous feeding, according to the diet in the active process. Based on the results, it can be stated that the VSI and HSI are both important indicators of fish condition status. The results found here may be useful in both fishery research and fishery management

Rare Copy Number Variants in Array-Based Comparative Genomic Hybridization in Early-Onset Skeletal Fragility

Early-onset osteoporosis is characterized by low bone mineral density (BMD) and fractures since childhood or young adulthood. Several monogenic forms have been identified but the contributing genes remain inadequately characterized. In search for novel variants and novel candidate loci, we screened a cohort of 70 young subjects with mild to severe skeletal fragility for rare copy-number variants (CNVs). Our study cohort included 15 subjects with primary osteoporosis before age 30 years and 55 subjects with a pathological fracture history and low or normal BMD before age 16 years. A custom-made high-resolution comparative genomic hybridization array with enriched probe density in >1,150 genes important for bone metabolism and ciliary function was used to search for CNVs. We identified altogether 14 rare CNVs. Seven intronic aberrations were classified as likely benign. Five CNVs of unknown clinical significance affected coding regions of genes not previously associated with skeletal fragility (ETV1-DGKB, AGBL2, ATM, RPS6KL1-PGF, and SCN4A). Finally, two CNVs were pathogenic and likely pathogenic, respectively: a 4 kb deletion involving exons 1-4 of COL1A2 (NM_000089.3) and a 12.5 kb duplication of exon 3 in PLS3 (NM_005032.6). Although both genes have been linked to monogenic forms of osteoporosis, COL1A2 deletions are rare and PLS3 duplications have not been described previously. Both CNVs were identified in subjects with significant osteoporosis and segregated with osteoporosis within the families. Our study expands the number of pathogenic CNVs in monogenic skeletal fragility and shows the validity of targeted CNV screening to potentially pinpoint novel candidate loci in early-onset osteoporosis.Peer reviewe

Metagenomic profiling of ticks: Identification of novel rickettsial genomes and detection of tick-borne canine parvovirus

Background: Across the world, ticks act as vectors of human and animal pathogens. Ticks rely on bacterial endosymbionts, which often share close and complex evolutionary links with tick-borne pathogens. As the prevalence, diversity and virulence potential of tick-borne agents remain poorly understood, there is a pressing need for microbial surveillance of ticks as potential disease vectors. Methodology/Principal Findings: We developed a two-stage protocol that includes 16S-amplicon screening of pooled samples of hard ticks collected from dogs, sheep and camels in Palestine, followed by shotgun metagenomics on individual ticks to detect and characterise tick-borne pathogens and endosymbionts. Two ticks isolated from sheep yielded an abundance of reads from the genus Rickettsia, which were assembled into draft genomes. One of the resulting genomes was highly similar to Rickettsia massiliae strain MTU5. Analysis of signature genes showed that the other represents the first genome sequence of the potential pathogen Candidatus Rickettsia barbariae. Ticks from a dog and a sheep yielded draft genome sequences of Coxiella strains. A sheep tick yielded sequences from the sheep pathogen Anaplasma ovis, while Hyalomma ticks from camels yielded sequences belonging to Francisella-like endosymbionts. From the metagenome of a dog tick from Jericho, we generated a genome sequence of a canine parvovirus. Significance: Here, we have shown how a cost-effective two-stage protocol can be used to detect and characterise tick-borne pathogens and endosymbionts. In recovering genome sequences from an unexpected pathogen (canine parvovirus) and a previously unsequenced pathogen (Candidatus Rickettsia barbariae), we demonstrate the open-ended nature of metagenomics. We also provide evidence that ticks can carry canine parvovirus, raising the possibility that ticks might contribute to the spread of this troublesome virus

PLS3 sequencing in childhood-onset primary osteoporosis identifies two novel disease-causing variants

The Summary Altogether 95 children with primary bone fragility were screened for variants in PLS3, the gene underlying X-linked osteoporosis. Two children with multiple peripheral and spinal fractures and low BMD had novel disease-causing PLS3 variants. Children with milder phenotypes had no pathogenic variants. PLS3 screening is indicated in childhood-onset primary osteoporosis. Introduction The study aimed to determine the role of pathogenic PLS3 variants in children's bone fragility and to elucidate the associated phenotypic features. Methods Two cohorts of children with bone fragility were screened for variants in PLS3, the gene underlying X-linked osteoporosis. Cohort I comprised 31 patients with childhood-onset primary osteoporosis of unknown etiology. Cohort II comprised 64 children who had sustained multiple fractures but were otherwise healthy. Clinical and radiological data were reviewed. Peripheral blood DNA was Sanger sequenced for coding exons and flanking intronic regions of PLS3. Results In two patients of cohort I, where other common genetic causes had been excluded, we identified two novel disease-causing PLS3 variants. Patient 1 was a male with bilateral femoral fractures at 10 years, low BMD (Z-score -4.1; 18 years), and multiple vertebral compression fractures. He had a novel nonsense variant in PLS3. Patient 2 was a girl with multiple long bone and vertebral fractures and low BMD (Z-score -6.6 at 6 years). She had a de novo missense variant in PLS3; whole exome sequencing and array-CGH identified no other genetic causes. Iliac crest bone biopsies confirmed low-turnover osteoporosis in both patients. In cohort II, no pathogenic PLS3 variants were identified in any of the subjects. Conclusion Two novel disease-causing variants in PLS3 were identified in a boy and a girl with multiple peripheral and spinal fractures and very low BMD while no pathogenic variants were identified in children with less severe skeletal fragility. PLS3 screening is warranted in male and female patients with childhood-onset primary osteoporosis.Peer reviewe