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Purpose: To describe a unique case of Purtscher-like retinopathy after a severe, complicated COVID-19 course which included development of disseminated intravascular coagulation (DIC). Observations: A 58-year-old male developed blurry vision in the left eye one week after being discharged from the hospital for severe COVID-19 pneumonia and DIC. He had been intubated and ventilated for 5 days. Fundus examination revealed optic nerve hyperemia in the right eye, optic nerve pallor in the left eye, arteriolar attenuation, multiple cotton wool spots and ill-defined areas of retinal whitening in the posterior pole in both eyes. His exam findings were most consistent with Purtscher-like retinopathy in both eyes. Conclusions and Importance: While several cases of central retinal artery and vein occlusion have been described in COVID-19 patients thus far, there has not been any reported cases of Purtscher-like retinopathy. To the best of our knowledge, this is the first case of Purtscher-like retinopathy in a patient who developed DIC during a severe COVID-19 infection.

Epigenetics is a rapidly developing field focused on deciphering chemical fingerprints that accumulate on human genomes over time. As the nascent idea of precision medicine expands to encompass epigenetic signatures of diagnostic and prognostic relevance, there is a need for methodologies that provide high-throughput DNA methylation profiling measurements. Here we report a novel quantification methodology for computationally reconstructing site-specific CpG methylation status from next generation sequencing (NGS) data using methyl-sensitive restriction endonucleases (MSRE). An integrated pipeline efficiently incorporates raw NGS metrics into a statistical discrimination platform to identify functional linkages between shifts in epigenetic DNA methylation and disease phenotypes in samples being analyzed. In this pilot proof-of-concept study we quantify and compare DNA methylation in blood serum of individuals with Parkinson's Disease relative to matched healthy blood profiles. Even with a small study of only six samples, a high degree of statistical discrimination was achieved based on CpG methylation profiles between groups, with 1,008 statistically different CpG sites (p textless 0.0025, after false discovery rate correction). A methylation load calculation was used to assess higher order impacts of methylation shifts on genes and pathways and most notably identified FGF3, FGF8, HTT, KMTA5, MIR8073, and YWHAG as differentially methylated genes with high relevance to Parkinson's Disease and neurodegeneration (based on PubMed literature citations). Of these, KMTA5 is a histone methyl-transferase gene and HTT is Huntington Disease Protein or Huntingtin, for which there are well established neurodegenerative impacts. The future need for precision diagnostics now requires more tools for exploring epigenetic processes that may be linked to cellular dysfunction and subsequent disease progression.

Pyrroindomycins A and B were isolated from fermentations of culture LL-42D005, a strain of Streptomyces rugosporus. Pyrroindomycins possess potent antimicrobial activities against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci. Their structures have been determined by using 1- and 2-D NMR, mass spectroscopy and chemical degradations. Pyrroindomycins are the first natural products that contain the highly unsaturated pyrroloindole moiety.

A new antitumor antibiotic, LL-C10037 alpha was isolated from the fermentation filtrate of a Streptomyces by adsorption, partition and reverse phase column chromatography. Its chemical structure was determined by 1H NMR, 13C NMR, UV, IR and mass spectral data. LL-C10037 alpha is a gamma-aminoepoxysemiquinone and is related to the epoxyguinone class of antibiotics.

The biosynthesis of maduramicin alpha and beta in a culture of Actinomadura yumaensis has been studied using 13C, 14C and 18O labeled precursors. The alpha component of this recently discovered polyether antibiotic, containing forty-seven carbon atoms in a seven-ring system, is derived from eight acetate, seven propionate and four methionine molecules. The beta component which is missing one methoxy group incorporates three methionine methyl groups. The carbohydrate moiety was enriched by methionine, but not significantly by acetate or propionate. Studies of the incorporation of 13C labeled precursors permit the 13C NMR assignment of maduramicin. The origin of oxygen atoms of maduramicin has been examined by feeding [1-13C, 18O2]acetate and [1-13C, 18O2]propionate separately in the fermentation culture and the resulting doubly labeled maduramicin samples were analyzed by the isotopic shifts in the 13C NMR spectra. These results are consistent with the initial formation of a triene, which is converted to maduramicin by cyclization of the triepoxide.

The behavior of the free acid and ammonium salt of maduramicin towards heat and alcohols is examined. In refluxing lower alcohols the free acid material is decarboxylated. In addition a bisketal decarboxylated compound as well as an A-ring monoketal decarboxylated derivative are formed. Heating the ammonium salt of the ionophores in suspension in water, or dissolved in inert solvents such as heptane or xylene can cause decarboxylation as well as concomitant dehydration of the F-ring. Reaction of dansyl chloride with the free acid of maduramicin can cause dehydration of the B-ring under very mild conditions.

A new family of antiparasitic macrolides has been isolated from Streptomyces cyaneogriseus sp. noncyanogenus. The compounds, designated LL-F28249 alpha, beta, gamma and lambda, possess potent antiparasitic activity. The isolation, purification and structure determination by spectroscopic methods are presented.

The formation of monovalent and divalent salt complexes of maduramicin is described and the 13C NMR chemical shift assignments of these materials are tabulated and discussed. In the spectrum of the thallium salt, 20 of the 47 signals are split due to the thallium-carbon coupling. Similarly the preparation of both the free acid and the sodium salt complexes of the normal methyl and ethyl ketal derivatives of maduramicin are outlined. Their 13C NMR spectra are fully assigned together with discussion of displacements observed due to this derivatization.

The isolation and characterization of many of the components of the avoparcin complex are described. A number of mild degradations products from this complex are similarly treated. Conditions for the analytical and preparative HPLC resolution of these materials are outlined.