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Pollinators represent one of the main agents of selection on floral traits. Here, we estimated phenotypic selection on floral morphology and phenology in a sympatric population of two orchid species, Platanthera bifolia and P. chlorantha, including enigmatic individuals with intermediate column morphology (as reflected by the distance between viscidia and caudicle length, two traits involved in assortative mating and reproductive isolation among Platanthera species), but genetically indistinguishable from P. bifolia. Our aim was to clarify whether the occurrence of intermediate phenotypes could be explained by the presence of selective pressures exerted by pollinators. Simple linear and quadratic regressions together with univariate and multivariate analyses were used to evaluate the strength of directional, disruptive and stabilizing selection. We found that selection on phenotypic traits varied between groups and sex functions. Contrary to our hypothesis, selection on the viscidia distance and caudicle length appeared to be consistent in the two P. bifolia groups. Interestingly, the viscidia distance was under significant stabilizing selection through female reproductive success in intermediate individuals. Based on these results, we conclude that, despite a significant selective pressure on some phenotypic traits, the presence of individuals with intermediate phenotype is not due to selection. Stabilizing selection on distance between viscidia in intermediate individuals may suggest that assortative mating play a role in the maintenance of this phenotypic polymorphism. [ABSTRACT FROM AUTHOR]

The small Ras-related GTPase Rab-28 is highly expressed in photoreceptor cells, where it possibly participates in membrane trafficking. To date, six alterations in the RAB28 gene have been associated with autosomal recessive cone-rod dystrophies. Confirmed variants include splicing variants, missense and nonsense mutations. Here, we present a thorough phenotypical and genotypical characterization of five individuals belonging to four Italian families, constituting the largest cohort of RAB28 patients reported in literature to date. All probands displayed similar clinical phenotype consisting of photophobia, decreased visual acuity, central outer retinal thinning, and impaired color vision. By sequencing the four probands, we identified: a novel homozygous splicing variant; two novel nonsense variants in homozygosis; a novel missense variant in compound heterozygous state with a previously reported nonsense variant. Exhaustive molecular dynamics simulations of the missense variant p.(Thr26Asn) in both its active and inactive states revealed an allosteric structural mechanism that impairs the binding of Mg2+, thus decreasing the affinity for GTP. The impaired GTP-GDP exchange ultimately locks Rab-28 in a GDP-bound inactive state. The loss-of-function mutation p.(Thr26Asn) was present in a compound heterozygosis with the nonsense variant p.(Arg137*), which does not cause mRNA-mediated decay, but is rather likely degraded due to its incomplete folding. The frameshift p.(Thr26Valfs4*) and nonsense p.(Leu13*) and p.(Trp107*) variants, if translated, would lack several key structural components necessary for the correct functioning of the encoded protein. [ABSTRACT FROM AUTHOR]

Background: Blepharoconjunctivitis poses a diagnostic challenge due to its diverse etiology, including viral infections. Blepharoconjunctivits can be acute or chronic, self-limiting, or needing medical therapy., Aim: To review possible viral agents crucial for accurate differential diagnosis in cases of blepharoconjunctivitis., Methods: The PubMed database was searched for records relating to viral blepharoconjunctivitis. The search string generated was "("virally"[All Fields] OR "virals"[All Fields] OR "virology"[MeSH Terms] OR "virology"[All Fields] OR "viral"[All Fields]) AND "Blepharoconjunctivitis"[All Fields]"., Results: A total of 24 publications were generated from the search string. Reference lists from each relevant article were also searched for more information and included in this review. Viral etiologies such as adenovirus, herpes simplex virus (HSV), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV) are frequently implicated. Adenoviral infections manifest with follicular conjunctivitis and preauricular lymphadenopathy, often presenting as epidemic keratoconjunctivitis. HSV and VZV infections can result in herpetic keratitis and may exhibit characteristic dendritic corneal ulcers. EBV, although less common, can cause unilateral or bilateral follicular conjunctivitis, particularly in immunocompromised individuals. Other potential viral agents, such as enteroviruses and molluscum contagiosum virus, should also be considered, especially in pediatric cases., Conclusion: Prompt recognition of these viral etiologies is essential for appropriate management and prevention of complications. Thus, a thorough understanding of the clinical presentation, epidemiology, and diagnostic modalities is crucial for accurate identification and management of viral blepharoconjunctivitis., Competing Interests: Conflict-of-interest statement: All authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Autologous blood therapy has emerged as a promising modality in managing ocular surface disorders. This review provides a comprehensive overview of the current literature regarding the use of autologous blood in ocular surface disorders, encompassing its physiological basis, clinical applications, techniques, challenges, and future perspectives. The ocular surface, comprising the cornea, conjunctiva, and tear film, plays a critical role in maintaining visual function, and its disruption can lead to various pathological conditions. With its rich composition of growth factors, cytokines, and other bioactive molecules, autologous blood offers therapeutic potential in promoting corneal wound healing, reducing inflammation, and improving tear film stability. Clinical studies have demonstrated the efficacy and safety of autologous blood therapy in diverse ocular surface disorders, including persistent epithelial defects, neurotrophic keratopathy, and dry eye disease. However, challenges such as variability in treatment response, adverse effects, and optimal patient selection remain areas of concern. Further research is needed to elucidate the underlying mechanisms of action, refine treatment protocols, and explore synergistic approaches with other therapeutic modalities. Despite these challenges, autologous blood therapy holds promise as a valuable adjunctive treatment option for ocular surface disorders, offering new avenues for improving patient outcomes and quality of life. This review examines the mechanisms underlying ocular surface disorders while discussing existing autologous blood-based therapies for managing these disorders. Current clinical trials are also summarized, and a comparison between autologous blood therapy and conventional eyedrops is attempted. Finally, safe techniques and protocols for autologous blood medicine are elucidated, and adverse effects and future perspectives of this novel therapy are reviewed., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Corneal injuries, which make up 3% of emergency room visits, can vary from small scratches to exposure or trauma-related damage that might be fatal to vision. Mechanical trauma, diseases of the eyelids, neurotrophic abnormalities, and chemical burns are common causes. A thorough examination is necessary for an accurate diagnosis and treatment plan. The goal of this study is to review corneal damage from both functional and traumatic causes associated with eyelid problems and surgical therapy. Based on a comprehensive analysis of the literature, it focuses on identifying important eyelid diseases that can compromise the integrity of the corneal epithelium, including entropion, ectropion, trichiasis, distichiasis, epiblepharon, and lagophthalmos. To find research on surgical care of eyelid disorders resulting in corneal injury, the MEDLINE and Reference Citation Analysis databases were searched (from 2008 to the present). At least two impartial reviewers examined every article to guarantee that all pertinent articles were found. Relevant publications were found using a literature search. Each pertinent paper's reference list was manually checked to include relevant documents the original search missed. There were 28 papers about surgical management of eyelid abnormalities that could jeopardize the integrity of the corneal epithelium: entropion, ectropion, trichiasis, distichiasis, epiblepharon, and lagophthalmos. Entropion treatment was the subject of the majority of these studies. The review strongly emphasizes determining the precise anatomical source of corneal injury in disorders of the eyelids and customizing surgical techniques accordingly. Cooperation between plastic surgeons and ophthalmologists is crucial to manage complicated situations and guarantee stable, long-term results., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Chronic wounds and non-healing tissue defects pose significant clinical challenges, necessitating innovative therapeutic approaches. A comprehensive literature review of amniotic membrane transplantation for wound healing and tissue repair evaluates the efficacy and safety of amniotic membrane transplantation in enhancing wound healing and tissue repair. Amniotic membranes promote wound closure and reduce inflammation and scarring via abundant growth factors, cytokines, and extracellular matrix components, which foster conducive environments for tissue regeneration. Amniotic membrane transplantation is effective in various medical disciplines, including ophthalmology, dermatology, and orthopedics. Low immunogenicity and anti-microbial properties ensure their safe application. Amniotic membrane transplantation offers a promising therapeutic approach for wound healing and tissue repair, and further research is warranted to explore its regenerative potential fully., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Age-related macular degeneration (AMD) is one of the leading causes of visual loss in older patients. No effective drug is available for this pathology, but studies about therapy with stem cells replacing the damaged retinal cells with retinal pigment epithelium (RPE) were described. The documentation of AMD progression and the response to stem cell therapy have been performed by optical coherence tomography, microperimetry, and other diagnostic technologies.This chapter reports a clinical review of the most important clinical trials and protocols regarding the use of stem cells in AMD., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background and Aims: Intestinal fibrosis, a frequent complication of inflammatory bowel disease, is characterized by stricture formation with no pharmacological treatment to date. N-acylethanolamine acid amidase (NAAA) is responsible of acylethanolamides (AEs, e.g., palmitoylethanolamide and oleoylethanolamide) hydrolysis. Here, we investigated NAAA and AEs signalling in gut fibrosis., Methods: NAAA and AEs signalling were evaluated in human intestinal specimens from stenotic Crohn's diseases (CD) patients. Gut fibrosis was induced by TNBS, monitored by colonoscopy and unascertained by qRT-PCR, histological analyses, and confocal microscopy. Immune cells were analysed in mesenteric lymph nodes by FACS. Colonic fibroblasts were cultured in conditioned media derived from polarized or not bone marrow-derived macrophages (BMDM). IL-23 signalling was evaluated by qRT-PCR, ELISA, FACS, and western blot in BMDM and in lamina propria CX3CR1+ cells., Results: In ileocolonic human CD strictures, increased transcript expression of NAAA was observed with a decrease of its substrates OEA and PEA. NAAA inhibition reduced intestinal fibrosis in vivo, as revealed by decrease in inflammatory parameters, collagen deposition and fibrosis genes, including epithelial to mesenchymal transition. More in-depth studies revealed modulation of the immune response related to IL-23 following NAAA inhibition. The antifibrotic actions of NAAA inhibition are mediated by Mφ and M2 macrophages that indirectly affect fibroblast collagenogenesis. NAAA inhibitor AM9053 normalized IL-23 signalling in BMDM and in lamina propria CX3CR1+ cells., Conclusions: Our findings provide new insights into the pathophysiological mechanism of intestinal fibrosis and identify NAAA as a promising target for the development of therapeutic treatments to alleviate CD fibrosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This review explores the connection between the ocular surface microbiome and glaucoma, highlighting its impact on disease progression. Beginning with an overview of global glaucoma significance, it emphasizes the importance of understanding the cellular characteristics and microbiology of the ocular microbiome. A search was conducted on the PubMed and Cochrane Library databases using the phrase "ocular microbiome glaucoma". 0 records were returned from the Cochrane Library while 21 were returned from PubMed. A total of 21 results were retrieved from 2017 to 2024. This comprised one opinion paper, four original research articles, and 16 reviews. This review covered the anatomy of the ocular surface, advanced analysis methods, and the ocular microbiome. It also delved into dysbiosis in glaucoma, addressing altered microbial communities and their potential role in disease progression. The intricate interplay between the ocular microbiome and the host's immune system is explored, emphasizing crosstalk and inflammatory responses. The review concludes by discussing therapeutic implications, including modulating ocular microbiota and potential future treatment strategies. Understanding the microbiome in healthy and glaucomatous eyes can help researchers and clinicians in innovative approaches to ocular health., Competing Interests: The authors declare no conflict of interest. Dario Rusciano worked for Fidia Ophthalmics before retirement and declares no conflict of interest. Given his role as Guest Editor and Editorial Board member, Dario Rusciano had no involvement in the peer-review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Adrian Gericke., (© 2024 The Author(s). Published by IMR Press.)

Background: Identification of latent tuberculosis infection (LTBI) is a critical step of tuberculosis surveillance, especially in low-incidence countries. However, it is limited to situations with a higher probability of developing active disease, e.g., patients with hematological malignancies. According to guidelines, in TB non-endemic countries, no clear screening program is established at diagnosis for patients with acute leukemia (AL). The primary endpoint of this study was to establish the prevalence of LTBI in patients with a diagnosis of AL using QuantiFERON (QFT)-TB. Secondarily, radiological and clinical features driving the increased risk of LTBI were evaluated., Methods: QFT-TB screening was performed before induction or consolidation in all patients with AL (myeloid and lymphoid) treated at our Institution between October 2019 and August 2023., Results: We accrued 62 patients, of whom 7 (11,3%) tested positive, without any symptoms or signs of active TB, and 2 (3,2%) resulted as indeterminate. All positive patients started prophylaxis with isoniazid 300 mg daily, while patients whose test was indeterminate did not receive any prophylaxis. Active TB was excluded by imaging, as well as microscopic, cultural, and molecular examination on bronchoalveolar lavage if signs of any infection were detected. During the 46 months of observation, no patients developed TB reactivation., Conclusions: Despite the low sample size, 1/10 of our patients had prior TB exposure, hinting that LTBI could be more common than expected in Italy. This finding suggests implementing TB screening in the pre-treatment setting, particularly at a time when more active treatments are becoming available also for patients ineligible for intensive chemotherapy., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Introduction: The purpose of this project was to explore the current standards of clinical care genetic testing and counseling for patients with inherited retinal diseases (IRDs) from the perspective of leading experts in selected European countries. Also, to gather opinions on current bottlenecks and future solutions to improve patient care., Methods: On the initiative of the European Vision Institute, a survey questionnaire with 41 questions was designed and sent to experts in the field from ten European countries. Each participant was asked to answer with reference to the situation in their own country., Results: Sixteen questionnaires were collected by November 2023. IRD genetic tests are performed in clinical care settings for 80% or more of tested patients in 9 countries, and the costs of genetic tests in clinical care are covered by the public health service to the extent of 90% or more in 8 countries. The median proportion of patients who are genetically tested, the median rate of genetically solved patients among those who are tested, and the median proportion of patients receiving counseling are 51-70%, 61-80%, and 61-80%, respectively. Improving the education of healthcare professionals who facilitate patient referrals to specialized centers, improving access of patients to more thorough genotyping, and increasing the number of available counselors were the most advocated solutions., Conclusion: There is a significant proportion of IRD patients who are not genetically tested, whose genetic testing is inconclusive, or who do not receive counseling. Educational programs, greater availability of state-of-the-art genotyping and genetic counselors could improve healthcare for IRD patients., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Sulfated glycosaminoglycans (GAGs) are fundamental constituents of both the cell surface and extracellular matrix. By playing a key role in cell-cell and cell-matrix interactions, GAGs are involved in many physiological and pathological processes. To design GAG mimetics with similar therapeutic potential as the natural ones, the specific structural features, among them sulfate content, sulfation pattern, and chain length, should be considered. In the present study, we describe a sulfation method based on microwave radiation to obtain highly sulfated derivatives as GAG mimetics. The starting low-molecular-weight (LMW) derivative was prepared from the infernan exopolysaccharide, a highly branched naturally slightly sulfated heteropolysaccharide synthesized by the deep-sea hydrothermal vent bacterium Alteromonas infernus . LMW highly sulfated infernan derivatives obtained by conventional heating sulfation have already been shown to display GAG-mimetic properties. Here, the potential of microwave-assisted sulfation versus that of the conventional method to obtain GAG mimetics was explored. Structural analysis by NMR revealed that highly sulfated derivatives from the two methods shared similar structural features, emphasizing that microwave-assisted sulfation with a 12-fold shorter reaction time is as efficient as the classical one.

Platanthera bifolia and P. chlorantha are terrestrial and rewarding orchids with a wide Eurasian distribution. Although genetically closely related, they exhibit significant morphological, phenological and ecological differences that maintain reproductive isolation between the species. However, where both species co-occur, individuals with intermediate phenotypic traits, often considered as hybrids, are frequently observed. Here, we combined neutral genetic markers (AFLPs), morphometrics and floral scent analysis (GC-MS) to investigate two mixed Platanthera populations where morphologically intermediate plants were found. Self-pollination experiments revealed a low level of autogamy and artificial crossings combined with assessments of fruit set and seed viability, showed compatibility between the two species. The results of the genetic analyses showed that morphologically intermediate plants had similar genetic patterns as the P. bifolia group. These results are corroborated also by floral scent analyses, which confirmed a strong similarity in floral scent composition between intermediate morphotypes and P. bifolia . Therefore, this study provided a much more detailed picture of the genetic structure of a sympatric zone between two closely allied species and supports the hypothesis that intermediate morphotypes in sympatry could reflect an adaptive evolution in response to local pollinator-mediated selection., Competing Interests: The authors declare there are no competing interests.

Background: Congenital fibiosis of the extraocular muscles (CFEOMI) refers to a group of congenital eye movement disorders that are characterized by non-progressive restrictive ophthalmoplegia. We present clinical and surgical data on affected members of a classic CFEOMI family., Methods: Ten members of a fifteen-member, three-generation Italian family affected by classic CFEOM participated in this study. Each affected family member underwent ophthalmologic (corrected visual acuity, pupillary function, anterior segment and fundus examination), orthoptic (cover test, cover-uncover test, prism alternate cover test), and preoperative examinations. Eight of the ten affected members had surgery and underwent postoperative examinations. Surgical procedures are listed., Results: All affected members were born with varying degrees of bilateral ptosis and ophthalmoplegia with both eyes fixed in a hypotropic position (classic CFEOM). The affected members clinical data prior to surgery, surgery procedures and postoperative outcomes are presented. On 14 operated eyes to correct ptosis there was an improvement in 12 eyes. In addition, the head position improved in all patients., Conclusions: Surgery is effective at improving ptosis in the majority of patients with classic CFEOM. However, the surgical approach should be individualized to each patient, as inherited CFEOM exhibits variable expressivity and the clinical features may differ markedly between affected individuals, even within the same family.