Review of Cutaneous Blastomycosis Seen in Wisconsin.

INTRODUCTION: Blastomycosis is a fungal infection caused by Blastomyces dermatitidis that is hyperendemic in Wisconsin. It commonly presents as a pulmonary infection and frequently disseminates to the skin. Studies evaluating the presentation and diagnosis of blastomycosis with skin as a presenting sign have not been thoroughly evaluated, and understanding the most accurate way to diagnose this infection is important for earlier therapeutic intervention. METHODS: This is a retrospective chart review study of a single institution. Subjects were identified through a search of ICD-9 (International Classification of Diseases, Ninth Revision) and ICD-10 (International Classification of Diseases, Tenth Revision) codes for blastomycosis in the clinical record and pathology database. Patients were included if diagnosed with cutaneous blastomycosis infection or involvement of the skin from systemic infection from January 1, 2009, to June 1, 2021. RESULTS: Twenty patients with a diagnosis of cutaneous involvement of blastomycosis were identified; 65% (n = 13) were male. Median age of diagnosis was 55.5 years. Fifty-five percent of patients were White, 35% were Black or African American. In addition to residence in an endemic area, 50% (n = 10) had exposure risk factors. Fifty percent of patients (n = 10) initially presented with a skin concerns; 65% (n = 13) had extracutaneous involvement. Diagnosis was made by histopathology alone in 55% (n = 11), culture plus histopathology in 35% (n = 7), and culture alone in 5% (n = 1) of cases. CONCLUSIONS: Our study highlighted similarities to those previously performed. Half of the patients (n = 10) who had cutaneous involvement of blastomycosis did not demonstrate clinically significant pulmonary involvement. Histopathology and culture remain critical in diagnosing cutaneous blastomycosis.

10-Alkoxy-anthracenyl-isoxazole analogs have sub-micromolar activity against a Glioblastoma multiforme cell line.

A series of 10-alkoxy-Anthryl-isoxazole-pyrrole-doubletails (RO-AIMs) were synthesized using a crown ether assisted nucleophilic aromatic substitution followed by a modified Schotten-Baumann reaction. The novel RO-AIMs described here exhibit robust growth inhibition for the human SNB19 CNS glioblastoma cell line, and biphenyl analog 8c had activity in the nanomolar regime, which represents the most efficacious compound in the AIM series to date. Computational modeling for RO-AIMs binding in a ternary complex with c-myc quadruplex DNA and its helicase DHX36 is presented which represents our current working hypothesis.

Identifiable Risk Factors to Minimize Postoperative Urinary Retention in Modern Outpatient Rapid Recovery Total Joint Arthroplasty.

BACKGROUND: Postoperative urinary retention (POUR) following total joint arthroplasty (TJA) presents a significant barrier to outpatient and early discharge TJA. This study examined the incidence and risk factors for acute POUR in a modern, evidence-based, outpatient, and early discharge TJA program. METHODS: Prospectively recorded data on 685 consecutive primary unilateral TJAs discharged the day of or day after surgery were retrospectively reviewed. POUR was diagnosed by a perioperative internal medicine specialist. Univariate analysis of potential predictors was performed, followed by binary logistic regression (BLR) testing of predictors with P ≤ .25. RESULTS: After exclusions for confounds, the final analysis sample consisted of 633 procedures. The overall incidence of POUR was 5.5% (3.9% for same day discharges). Male gender, history of urinary retention, use of rocuronium, use of glycopryrrolate, use of neostigmine, fentanyl spinals, and the absence of an indwelling urethral catheter were associated with acute POUR and met criteria for entry into multivariate BLR. Seventeen additional predictors, including kidney disease and outpatient surgery were unrelated to POUR. In the final BLR model (P = .001), male patients who received glycopyrrolate with neostigmine had a 34% probability of developing POUR, which declined to 2.8% in the absence of these risk factors. CONCLUSION: Despite a relatively low incidence of 5.5%, avoidance of anticholinergics and cholinesterase inhibitors during anesthesia should be carefully considered in outpatient TJA, particularly in stand-alone ambulatory surgery centers.

MicroRNA-135b Regulates Leucine Zipper Tumor Suppressor 1 in Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and it presents a therapeutic challenge in organ transplant recipient patients. Despite the need, there are only a few targeted drug treatment options. Recent studies have revealed a pivotal role played by microRNAs (miRNAs) in multiple cancers, but only a few studies tested their function in cSCC. Here, we analyzed differential expression of 88 cancer related miRNAs in 43 study participants with cSCC; 32 immunocompetent, 11 OTR patients, and 15 non-lesional skin samples by microarray analysis. Of the examined miRNAs, miR-135b was the most upregulated (13.3-fold, 21.5-fold; p=0.0001) in both patient groups. Similarly, the miR-135b expression was also upregulated in three cSCC cell lines when evaluated by quantitative real-time PCR. In functional studies, inhibition of miR-135b by specific anti-miR oligonucleotides resulted in upregulation of its target gene LZTS1 mRNA and protein levels and led to decreased cell motility and invasion of both primary and metastatic cSCC cell lines. In contrast, miR-135b overexpression by synthetic miR-135b mimic induced further down-regulation of LZTS1 mRNA in vitro and increased cancer cell motility and invasiveness. Immunohistochemical evaluation of 67 cSCC tumor tissues demonstrated that miR-135b expression inversely correlated with LZTS1 staining intensity and the tumor grade. These results indicate that miR-135b functions as an oncogene in cSCC and provide new understanding into its pathological role in cSCC progression and invasiveness.

Ethyl 3-(9-chloro-10-oxo-9,10-di-hydro-anthracen-9-yl)-5-methyl-isoxazole-4-carboxyl-ate.

The asymmetric unit of the title compound, C21H16ClNO4, contains two independent mol-ecules (A and B), each adopting a conformation wherein the isoxazole ring is roughly orthogonal to the anthrone ring. The dihedral angle between the mean plane of the isoxazole (all atoms) and the mean plane of the anthrone (all atoms) is 88.48 (3)° in one mol-ecule and 89.92 (4)° in the other. The ester is almost coplanar with the isoxazole ring, with mean-plane dihedral angles of 2.48 (15) and 8.62 (5)°. In both mol-ecules, the distance between the ester carbonyl O atom and the anthrone ketone C atom is about 3.3 Å. The anthrone ring is virtually planar (r.m.s. deviations of 0.070 and 0.065 Å) and adopts a shallow boat conformation in each mol-ecule, as evidenced by the sum of the six intra-B-ring torsion angles [41.43 (15) and 34.38 (15)° for molecules A and B, respectively]. The closest separation between the benzene moieties of anthrones A and B is 5.1162 (7) Å, with an angle of 57.98 (5)°, consistent with an edge-to-face π-stacking inter-action. In the crystal, weak C-H⋯O and C-H⋯N inter-actions link the mol-ecules, forming a three-dimensional network.

Synthesis of new quinolinequinone derivatives and preliminary exploration of their cytotoxic properties.

A series of 7-amino- and 7-acetamidoquinoline-5,8-diones with aryl substituents at the 2-position were synthesized, characterized, and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1) -directed antitumor agents. The synthesis of lavendamycin analogues is illustrated. Metabolism studies demonstrated that 7-amino analogues were generally better substrates for NQO1 than 7-amido analogues, as were compounds with smaller heteroaromatic substituents at the C-2 position. Surprisingly, only two compounds, 7-acetamido-2-(8'-quinolinyl)quinoline-5,8-dione (11) and 7-amino-2-(2-pyridinyl)quinoline-5,8-dione (23), showed selective cytotoxicity toward the NQO1-expressing MDA468-NQ16 breast cancer cells versus the NQO1-null MDA468-WT cells. For all other compounds, NQO1 protected against quinoline-5,8-dione cytotoxicity. Compound 22 showed potent activity against human breast cancer cells expressing or not expressing NQO1, with respective IC50 values of 190 nM and 140 nM and a low NQO1-mediated reduction rate, which suggests that the mode of action of 22 differs from that of lavendamycin and involves an unidentified target(s).

A synthetic superoxide dismutase/catalase mimetic EUK-207 mitigates radiation dermatitis and promotes wound healing in irradiated rat skin.

In the event of a radionuclear attack or nuclear accident, the skin would be the first barrier exposed to radiation, though skin injury can progress over days to years following exposure. Chronic oxidative stress has been implicated as being a potential contributor to the progression of delayed radiation-induced injury to skin and other organs. To examine the causative role of oxidative stress in delayed radiation-induced skin injury, including impaired wound healing, we tested a synthetic superoxide dismutase (SOD)/catalase mimetic, EUK-207, in a rat model of combined skin irradiation and wound injury. Administered systemically, beginning 48 hours after irradiation, EUK-207 mitigated radiation dermatitis, suppressed indicators of tissue oxidative stress, and enhanced wound healing. Evaluation of gene expression in irradiated skin at 30 days after exposure revealed a significant upregulation of several key genes involved in detoxication of reactive oxygen and nitrogen species. This gene expression pattern was primarily reversed by EUK-207 therapy. These results demonstrate that oxidative stress has a critical role in the progression of radiation-induced skin injury, and that the injury can be mitigated by appropriate antioxidant compounds administered 48 hours after exposure.

Ethyl 3-(10-bromo-anthracen-9-yl)-5-methyl-1,2-oxazole-4-carboxyl-ate.

In the title compound, C21H16BrNO3, the mean planes of the anthracene tricycle and isoxazole ring are inclined to each other at a dihedral angle of 72.12 (7)°. The carb-oxy group is slightly out of the isoxazole mean plane, with a maximum deviation of 0.070 (5) Šfor the carbonyl O atom. In the crystal, pairs of weak C-H⋯O hydrogen bonds link the mol-ecules into dimers, and weak C-H⋯N inter-actions further link these dimers into corrugated layers parallel to the bc plane.

Ion-pair triple helicates and mesocates self-assembled from ditopic 2,2'-bipyridine-bis(urea) ligands and Ni(II) or Fe(II) sulfate salts.

NiSO(4) and FeSO(4) self-assemble with heteroditopic ligands (L) comprising 2,2'-bipyridine and o-phenylene-(bis)urea cation- and anion-binding sites, respectively, into [ML(3)SO(4)] (M = Ni(2+), Fe(2+)) triple-stranded ion-pair helicates and mesocates.

Urea-functionalized M4L6 cage receptors: anion-templated self-assembly and selective guest exchange in aqueous solutions.

We present an extensive study of a novel class of de novo designed tetrahedral M(4)L(6) (M = Ni, Zn) cage receptors, wherein internal decoration of the cage cavities with urea anion-binding groups, via functionalization of the organic components L, led to selective encapsulation of tetrahedral oxoanions EO(4)(n-) (E = S, Se, Cr, Mo, W, n = 2; E = P, n = 3) from aqueous solutions, based on shape, size, and charge recognition. External functionalization with tBu groups led to enhanced solubility of the cages in aqueous methanol solutions, thereby allowing for their thorough characterization by multinuclear ((1)H, (13)C, (77)Se) and diffusion NMR spectroscopies. Additional experimental characterization by electrospray ionization mass spectrometry, UV-vis spectroscopy, and single-crystal X-ray diffraction, as well as theoretical calculations, led to a detailed understanding of the cage structures, self-assembly, and anion encapsulation. We found that the cage self-assembly is templated by EO(4)(n-) oxoanions (n ≥ 2), and upon removal of the templating anion the tetrahedral M(4)L(6) cages rearrange into different coordination assemblies. The exchange selectivity among EO(4)(n-) oxoanions has been investigated with (77)Se NMR spectroscopy using (77)SeO(4)(2-) as an anionic probe, which found the following selectivity trend: PO(4)(3-) ≫ CrO(4)(2-) > SO(4)(2-) > SeO(4)(2-) > MoO(4)(2-) > WO(4)(2-). In addition to the complementarity and flexibility of the cage receptor, a combination of factors have been found to contribute to the observed anion selectivity, including the anions' charge, size, hydration, basicity, and hydrogen-bond acceptor abilities.