Synthesis of substituted 2H-Chromenes via Pd-catalyzed C-H activation and thermal cyclization.

A proficient approach has been developed for the synthesis of substituted 2H-chromenes from C1-substituted glucal. The key step of our synthetic methodology was C-H activation in propylene carbonate solvent followed by 6π-electrocyclization aromatization in ethylene glycol as greener substitutes to toxic aprotic solvents, to obtain 2H-chromenes in a stepwise manner. The application of the developed methodology was further explored with the synthesis of a small library of substituted 2H-chromenes in good yields.

A Case Report of Squamous Cell Carcinoma Misdiagnosed as Cryptogenic Organizing Pneumonia.

After adenocarcinoma, squamous cell lung cancer is the most common type of non-small cell lung cancer (NSCLC) among non-smokers. A tissue biopsy followed by imaging (chest X-ray, computed tomography (CT) lung, and positron emission tomography (PET) scan) is the best modality for confirmation and staging of the disease. Sometimes, the histopathological appearance of squamous cell lung carcinoma (SCLC) can be confused with organizing pneumonia. Such findings can delay the diagnosis of SCLC, which can affect the treatment and course of the disease. Any lung mass that is highly suspicious for carcinoma should be closely monitored with imaging, and a repeat tissue biopsy should be done for a confirmation of the diagnosis to start appropriate therapy as soon as possible.

C-Glycopyranosyl aldehydes: emerging chiral synthons in organic synthesis.

Herein, we have summarized the vast array of synthetic processes that have been developed for the synthesis of C-glycopyranosyl aldehydes and diverse C-glycoconjugates derived from them by covering the literature reported from 1979 to 2023. Notwithstanding its challenging chemistry, C-glycosides are considered stable pharmacophores and are used as important bioactive molecules. The discussed synthetic methodologies to access C-glycopyranosyl aldehydes take advantage of seven key intermediates, viz. allene, thiazole, dithiane, cyanide, alkene, and nitromethane. Furthermore, the integration of complex C-glycoconjugates derived from varied C-glycopyranosyl aldehydes involves nucleophilic addition/substitution, reduction, condensation, oxidation, cyclo condensation, coupling, and Wittig reactions. In this review, we have categorized the synthesis of C-glycopyranosyl aldehydes and C-glycoconjugates on the basis of the methodology used for their synthesis and on types of C-glycoconjugates, respectively.

Dual-Action Heteromultivalent Glycopolymers Stringently Block and Arrest Influenza A Virus Infection In Vitro and Ex Vivo.

Here, we demonstrate the concerted inhibition of different influenza A virus (IAV) strains using a low-molecular-weight dual-action linear polymer. The 6'-sialyllactose and zanamivir conjugates of linear polyglycerol are optimized for simultaneous targeting of hemagglutinin and neuraminidase on the IAV surface. Independent of IAV subtypes, hemagglutination inhibition data suggest better adsorption of the heteromultivalent polymer than homomultivalent analogs onto the virus surface. Cryo-TEM images imply heteromultivalent compound-mediated virus aggregation. The optimized polymeric nanomaterial inhibits >99.9% propagation of various IAV strains 24 h postinfection in vitro at low nM concentrations and is up to 10000× more effective than the commercial zanamivir drug. In a human lung ex vivo multicyclic infection setup, the heteromultivalent polymer outperforms the commercial drug zanamivir and homomultivalent analogs or their physical mixtures. This study authenticates the translational potential of the dual-action targeting approach using small polymers for broad and high antiviral efficacy.

Role of point-of-care arterial blood potassium in diagnosing pseudohyperkalemia.

Hyperkalemia is a life-threatening emergency, but it needs to be differentiated from pseudohyperkalemia to avoid unnecessary treatment. We present a case of pseudohyperkalemia in a chronic lymphocytic leukemia patient with severe leukocytosis, highlighting the role of point-of-care potassium. Laboratory workup showed persistent hyperkalemia on analysis of venous blood samples even after treatment for hyperkalemia. Point-of-care potassium checks on whole arterial blood immediately after sampling were consistently in the normal range. Treatments for hyperkalemia were stopped to avoid life-threatening hypokalemia.

Gemcitabine-Induced Thrombotic Microangiopathy Managed Conservatively in a Patient of Breast Cancer.

Thrombotic microangiopathy (TMA) consists of a group of occlusive microvascular disorders, which include thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). TMA can be classified as primary or secondary based on the etiology. Gemcitabine-induced TMA is a rare side effect of the drug with varying clinical presentations. We present a case involving the classic triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and renal failure associated with gemcitabine. Gemcitabine was immediately stopped, and our patient's condition improved with conservative management.

Synthesis and Structural Characterization of 1-(E-1-Arylpropenon-3-yl)-3,4,6-tri-O-benzyl-d-glucals and Their Transformation into Pentasubstituted (2R,3S,4R)-Chromanes via Pd-Catalyzed Cross Dehydrogenative Coupling Reaction.

We have developed an efficient methodology for the synthesis of (2R,3S,4R)-2-hydroxymethyl-3,4-dihydroxy-6-aryl-7-aroylchromanes in which the chirality at the C-2, C-3, and C-4 positions is being drawn from C-glucopyranosyl aldehyde, which in turn can be efficiently synthesized from d-glucose. Thus, the synthesis starts with the transformation of sugar aldehyde into 1-(E-1-arylpropenon-3-yl)-3,4,6-tri-O-benzyl-d-glucals using Claisen-Schmidt type condensation reaction with different acetophenones and then to 1,2-disubstituted glucals via Pd(II)-catalyzed cross dehydrogenative coupling reaction, which in turn has been efficiently converted into (2R,3S,4R)-chromanes via 6π-electrocyclization and in situ dehydrogenative aromatization.

Clinical characteristics and outcomes of patients with Corona Virus Disease 2019 (COVID-19) at Mercy Health Hospitals, Toledo, Ohio.

IMPORTANCE: The ongoing pandemic of the novel Corona Virus Disease 2019 (COVID-19) is an unprecedented challenge to global health, never experienced before. OBJECTIVE: This study aims to describe the clinical characteristics and outcomes of patients with COVID-19 admitted to Mercy Hospitals. DESIGN AND METHODS: Retrospective, observational cohort study designed to include every COVID-19 subject aged 18 years or older admitted to Mercy Saint (St) Vincent, Mercy St Charles, and Mercy St Anne's hospital in Toledo, Ohio from January 1, 2020 through June 15th, 2020. Primary Outcome Measure was mortality in the emergency department or as an in-patient. RESULTS: 470 subjects including 224 males and 246 females met the inclusion criteria for the study. Subjects with the following characteristics had higher odds (OR) of death: Older age [OR 8.3 (95% CI 1.1-63.1, p = 0.04)] for subjects age 70 or more compared to subjects age 18-29); Hypertension [OR 3.6 (95% CI 1.6-7.8, p = 0.001)]; Diabetes [OR 3.1 (95% CI 1.7-5.6, p<0.001)]; COPD [OR 3.4 (95% CI 1.8-6.3, p<0.001)] and CKD stage 2 or greater [OR 2.5 (95% CI 1.3-4.9, p = 0.006)]. Combining all age groups, subjects with hypertension had significantly greater odds of the following adverse outcomes: requiring hospital admission (OR 2.2, 95% CI 1.4-3.4, p<0.001); needing respiratory support in 24 hours (OR 2.5, 95% CI: 1.7-3.7, p<0.001); ICU admission (OR 2.7, 95% CI 1.7-4.4, p<0.001); and death (OR 3.6, 95% CI 1.6-7.8, p = 0.001). Hypertension was not associated with needing vent in 24 hours (p = 0.07). CONCLUSION: Age and hypertension were associated with significant comorbidity and mortality in Covid-19 Positive patients. Furthermore, people who were older than 70, and had hypertension, diabetes, COPD, or CKD had higher odds of dying from the disease as compared to patients who hadn't. Subjects with hypertension also had significantly greater odds of other adverse outcomes.

Synthesis of Sugar Diene and Its Pd-Catalyzed Transformation into Chromanes.

A route to synthesize 1,2-disubstituted glucals has been developed, which were further converted to substituted chromanes by thermal 6π-electrocyclization in HMPA followed by in situ aromatization. One of the key steps in the synthesis of chromane is metal-free generation of C1-substituted glucal from d-mannose, which was further converted to 1,2-disubstituted glucals by Pd-catalyzed Fujiwara-Moritani reaction with styrenes, acrylates, acrylamide, acrylonitrile, and ethyl vinyl ketone in good yields.

Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides.

Conversion of D-glucose to 4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-ribofuranose, which is a key precursor for the synthesis of different types of bicyclic/spiro nucleosides, led to the formation of an inseparable 1:1 mixture of the desired product and 4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-xylofuranose. A convenient environment friendly Novozyme®-435 catalyzed selective acetylation methodology has been developed for the separation of an epimeric mixture of ribo- and xylotrihydroxyfuranosides in quantitative yields. The structure of both the monoacetylated epimers, i.e., 5-O-acetyl-4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-ribo- and xylofuranose obtained by enzymatic acetylation, has been confirmed by an X-ray study on their corresponding 4-C-p-toluenesulfonyloxymethyl derivatives. Furthermore, the two separated epimers were used for the convergent synthesis of two different types of bicyclic nucleosides, which confirms their synthetic utility.

Sugar-based novel chiral macrocycles for inclusion applications and chiral recognition.

A convergent template assisted synthesis of sugar-based chiral macrocycles has been achieved. The host-guest inclusion studies have revealed significant interactions of the synthesized macrocycle with primary over secondary ammonium salt. The chiral macrocyle also discriminates between D- and L-phenylalanine methyl ester hydrochlorides as revealed by (1)H NMR spectral studies on the mixture of the host and the guest molecules.

Synthesis of ß-C-Glycopyranosyl Aldehydes and 2,6-Anhydro-heptitols.

A convenient route has been developed for the diastereoselective synthesis of ß-C-glycopyranosyl aldehydes from D-glucose, D-mannose, and D-galactose. The key step in the synthesis of C-glycosyl aldehydes is the aryl driven reductive dehydration on 1-phenyl-2-(2',3',4',6'-tetra-O-acetyl-ß-D-glycopyranosyl)ethanone to afford alkenes, which on oxidation afford the desired compounds in good yield. ß-C-Glycopyranosyl aldehydes have been converted to 2,6-anhydro-heptitols in quantitative yields. The 2,6-anhydro-heptitols derived from D-mannose and D-galactose are enantiomeric and are useful linkers for the synthesis of macrocycles/amphiphiles of complementary chirality.

Diagnosing bacterial peritonitis made easy by use of leukocyte esterase dipsticks.

INTRODUCTION: Spontaneous bacterial peritonitis (SBP) requires rapid diagnosis for the initiation of antibiotics. Its diagnosis is usually based on manual examination of ascitic fluid (AF) having long reporting time. AF infection is diagnosed when the fluid polymorphonuclear leukocyte (PMNL) concentration ≥250 cells/mm(3). AIMS AND OBJECTIVES: Aim was to evaluate the diagnostic utility of leukocyte esterase (LE) reagent strip for rapid diagnosis of SBP in patients who underwent abdominal paracentesis and to calculate the sensitivity, specificity, positive, and negative predictive values. MATERIALS AND METHODS: The study was carried out on 103 patients with ascites. Cell count of AF as determined by colorimetric scale of Multistix 10 SG reagent strip was compared with counting chamber method (PMNL count ≥250 cells/mm(3) was considered positive). RESULTS AND OBSERVATIONS: Of the 103 patients SBP was diagnosed in 20 patients, 83 patients were negative for SBP by manual cell count. The sensitivity and specificity of the LE test for detecting neutrocytic SBP taking grade 2 as cut off were 95% and 96.4% respectively, with a positive predictive value of 86.4% and a negative predictive value of 98.8%. Diagnostic accuracy of LE test was 96.1%. DISCUSSION: There was a good correlation between the reagent strip result and PMNL count. The LE strip test is based on the esterase activity of activated granulocytes which reacts with an ester-releasing hydroxyphenylpyrrole causing a colour change in the azo dye of reagent strip. It is a very sensitive and specific method for the prompt detection of elevated PMNL count, and represents a convenient, inexpensive, simple, and bedside method for diagnosis of SBP. A negative LE test result excludes SBP with a high degree of certainty.

Prognostication in Pulmonary Arterial Hypertension with Submaximal Exercise Testing.

INTRODUCTION: The submaximal exercise test (SET), which gives both a measure of exercise tolerance, as well as disease severity, should be a more robust functional and prognostic marker than the six-minute walk test (6MWT). This study aimed to determine the prognostic value of SET as predicted by the validated REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Artery Hypertension Disease Management) registry risk score (RRRS). METHODS: Sixty-five consecutive patients with idiopathic and associated pulmonary arterial hypertension (PAH) underwent right-heart catheterization, echocardiogram, 6MWT and a three-minute SET (Shape-HF™). Analyses explored the association between SET variables and prognosis predicted by the RRRS. RESULTS: Although multiple SET variables correlated with the RRRS on univariate analyses, only VE/VCO2 (r = 0.57, p < 0.0001) remained an independent predictor in multivariate analysis (ß = 0.05, p = 0.0371). Additionally, the VE/VCO2 was the most discriminatory (area under receiver operating characteristic curve, 0.84) in identifying the highest-risk category (RRRS ≥ 10), with an optimal cut-off of 40.6, resulting in a high sensitivity (92%) and negative-predictive value (97%), but a lower specificity (67%). CONCLUSION: SETs, particularly the VE/VCO2, appear to have prognostic value when compared to the RRRS. If validated in prospective trials, SET should prove superior to the 6MWT or the RRRS, with significant implications for both future clinical trials and clinical practice.

Design and synthesis of LNA-based mercaptoacetamido-linked nucleoside dimers.

Three LNA-based mercaptoacetamido-linked nonionic nucleoside dimers TL-S-T, T-S-TL, and TL-S-TL have been synthesized by HOBT and HBTU catalyzed condensation of silyl-protected 2-S-(thymidin-5 '-yl)mercaptoacetic acid or 2-S-(2 '-O,4 '-C-methylenethymidin-5 '-yl)mercaptoacetic acid with 3 '-amino-3 '-deoxy-5 '-O-DMT-2 '-O,4 '-C-methylenethymidine or with 3 '-amino-3 '-deoxy-5 '-O-DMT-ß-thymidine followed by desilylation of the protected dimers. The 3 '-O-phosphoramidite derivative of one of the nucleoside dimers was successfully prepared by condensation with [P(-Cl)(-OCH2CH2CN)-N(iPr)2}] in DCM in the presence of N,N-diisopropylethylamine (DIPEA), which is a building block for the preparation of mercaptoacetamido-linked oligonucleotides of therapeutic applications.