Advantages of Early Surgical Management of Periorbital Infantile Hemangiomas.

Background: Early evaluation and treatment of periorbital infantile hemangiomas (POIH) were associated with lower rates of ophthalmological complications. Objective: To evaluate age and characteristics associated with improved anisometropic astigmatism (anisoastigmatism) and eye symmetry measured by diopters and a 5-point scale, respectively, in patients with POIH treated with surgical excision. Methods: A retrospective study was performed on patients with POIH. Patient characteristics and eye symmetry were analyzed between patients with resolved and unresolved anisoastigmatism after surgery. Statistical analyses included the Mann-Whitney U tests, chi-square tests, and linear regression models. Results: In total, 54 patients were included (male: 20, female: 34). Upper medial eyelid was the most commonly affected site (resolved: 45%, unresolved: 43%), followed by upper lateral and upper central. Fifty-six percent (31/55) had postoperative resolution of anisoastigmatism, whereas 44% (24/55) did not. Earlier surgical evaluation (median: 4.5 vs. 6.0 months, p = 0.047) and excision (median: 5.0 vs. 12.0 months, p = 0.005) were associated with reversible anisoastigmatism. Good and suboptimal eye symmetry were not associated with earlier surgical excision (median: 6 vs. 6.5 months, p = 0.87). Follow-up ranged from 1 month to 12 years. Conclusion: Earlier surgical excision was associated with reversing anisoastigmatism but was not significant for improving eye symmetry.

Evaluation of TrpM and PsiD substrate promiscuity reveals new biocatalytic capabilities.

N-methylated tryptamines, such as the hallucinogenic natural products, psilocybin and N,N-dimethyltryptamine (DMT), are gaining interest from the medical community due to their potential as next generation treatments for mental health disorders. The clinical relevance of these compounds has driven scientists to develop biosynthetic production routes to a number of tryptamine drug candidates, and efforts are ongoing to expand and further develop these biosynthetic capabilities. To that end, we have further characterized the substrate preferences of two enzymes involved in tryptamine biosynthesis: TrpM, a tryptophan N-methyltransferase from Psilocybe serbica, and PsiD, the gateway decarboxylase of the psilocybin biosynthesis pathway. Here, we show that TrpM can N-methylate the non-native amino acid substrate, 4-hydroxytryptophan, a key intermediate in the Escherichia coli-based recombinant psilocybin biosynthesis pathway. However, the ability to incorporate TrpM into a functional psilocybin biosynthesis pathway was thwarted by PsiD's inability to use N,N-dimethyl-4-hydroxytryptophan as substrate, under the culturing conditions tested, despite demonstrating activity on N-methylated and 4-hydroxylated tryptophan derivatives individually. Taken together, this work expands upon the known substrates for TrpM and PsiD, further increasing the diversity of tryptamine biosynthetic products.

"Biosynthesis of psilocybin and its nonnatural derivatives by a promiscuous psilocybin synthesis pathway in Escherichia coli".

Traditional psychedelics are undergoing a transformation from recreational drugs, to promising pharmaceutical drug candidates with the potential to provide an alternative treatment option for individuals struggling with mental illness. Sustainable and economic production methods are thus needed to facilitate enhanced study of these drug candidates to support future clinical efforts. Here, we expand upon current bacterial psilocybin biosynthesis by incorporating the cytochrome P450 monooxygenase, PsiH, to enable the de novo production of psilocybin as well as the biosynthesis of 13 psilocybin derivatives. The substrate promiscuity of the psilocybin biosynthesis pathway was comprehensively probed by using a library of 49 single-substituted indole derivatives, providing biophysical insights to this understudied metabolic pathway and opening the door to the in vivo biological synthesis of a library of previously unstudied pharmaceutical drug candidates.

Distribution and Clinical Characteristics of Periorbital Infantile Hemangiomas.

Background: Periorbital infantile hemangiomas (POIHs) are associated with a high incidence of visual complications. Objective(s): To analyze the sites of predilection of POIHs and to determine whether certain sites require earlier intervention due to their higher rate of visual complications. Methods: A retrospective case series study was conducted on patients from two tertiary care centers for 25 years. The location of POIHs was determined from clinical photographs, medical records, and radiological studies. The presence or absence of anisometropic astigmatism (anisoastigmatism) and amblyopia was recorded. Data were analyzed using a chi-square test. Results: There were 486 patients, of which 302 patients had ophthalmology evaluations and 245 patients had refractive error data. At presentation, 10% of patients already had amblyopia and 44% had anisoastigmatism. Medial eyelid lesions had the highest risk of developing anisoastigmatism (anisoastigmatism correlates with eyelid position, p = 0.0001). Segmental and upper medial lesions had the highest risk of amblyopia at initial evaluation. Conclusion: The site of POIH is an important indicator for developing clinically significant anisoastigmatism and amblyopia, underlining the need for early ophthalmologic assessment and management.