Synthetic Access to l-Guluronic Acid via Fluorine-Directed C-5 Epimerization.

l-Guluronic acid is integral to the structures of alginates and to the pathogenesis of . The exploitation of this hexose in both existing and new contexts is, however, limited by its prohibitively high commercial cost. We report on a short and efficient synthetic route to an l-GulA building block from a simple d-mannose thioglycoside.

Synthesis of a deuterated disaccharide internal standard for LC-MS/MS quantitation of heparan sulfate in biological samples.

High levels of heparan sulfate (HS) are a marker for several mucopolysaccharidosis (MPS) disorders which are lysosomal storage diseases caused by genetic defects in HS-degrading enzymes. Quantitation of HS in biological samples is therefore critical for diagnosis and evaluating the efficacy of new therapies. Herein we present the efficient synthesis of a butylated GlcN-GlcA disaccharide and its deuterated derivative for use as an internal standard in a quantitative mass spectrometry-based assay for analysis of HS following butanolysis.

Amphiphilic Heparinoids as Potent Antiviral Agents against SARS-CoV-2.

Herein, we report the synthesis and biological evaluation of a novel series of heparinoid amphiphiles as inhibitors of heparanase and SARS-CoV-2. By employing a tailor-made synthetic strategy, a library of highly sulfated homo-oligosaccharides bearing d-glucose or a C5-epimer (i.e.

Origins of Temperature-Dependent Anomeric Selectivity in Glycosylations with an L-Idose Thioglycoside.

L-Idose thioglycosides are useful glycosyl donors for the construction of glycosaminoglycan oligosaccharides. When activated with NIS and catalytic TMSOTf in the presence of methanol, the stereoselectivity of O-glycosylation displays an intriguing dependence on the reaction temperature, with an increased preference for formation of the α-glycoside at higher temperatures. Using a combination of vt-NMR spectroscopy and DFT calculations, we show how a simple mechanistic model, based on competing reactions of the iodinated thioglycoside, can explain the main features of the temperature dependence.

Site-Selective Photobromination of -Acetylated Carbohydrates in Benzotrifluoride.

Ferrier photobromination enables direct synthetic access to valuable 5--bromosugars but has limitations that restrict its broader use. The reaction is typically conducted in CCl heated at reflux with irradiation by broad spectrum, energy-inefficient heat lamps. Herein, we demonstrate that the reaction proceeds rapidly and efficiently with PhCF as a safe and environmentally benign alternative to CCl at mild temperatures (≤40 °C) inside a compact photoreactor fitted with purple light-emitting diodes (LEDs).

Impact of ACIST CVi contrast delivery system on iodinated contrast media administration and waste.

The COVID-19 pandemic led to disruptions in iodinated contrast media (ICM) production and produced a global product shortage in the spring of 2022. The ACIST CVi system is an automated contrast injector system approved by the FDA for multi-patient dosing of ICM from a single container. A transition from the traditional manifold system for contrast injection to the ACIST CVi automated injector system in our cardiac angiographic labs during the COVID-19 pandemic led to reductions in contrast waste and cost while limiting patient exposure to ICM.

The central pattern of weakness of ALS: Morphological correlates in whole-body muscle MRI.

Objective: Monosynaptically cortically innervated α-motoneurons are early and strongly involved in amyotrophic lateral sclerosis (ALS). Consequently, the muscles that receive the strongest direct corticomotoneuronal input are the clinically most affected. To objectify this concept in vivo through morphological image correlates, whole-body magnetic resonance imaging (MRI) with muscle signal analysis was performed in patients with ALS compared to healthy controls.

Changes in fecal elastase-1 following initiation of CFTR modulator therapy in pediatric patients with cystic fibrosis.

Background: Improvement in exocrine pancreatic function in persons with CF (pwCF) on cystic fibrosis transmembrane conductance regulator (CFTR) modulators has been documented in clinical trials using fecal pancreatic elastase-1 (FE-1). Our group endeavored to evaluate real-world data on FE-1 in children on CFTR modulator therapy at three pediatric cystic fibrosis (CF) centers.

Methods: Pediatric pwCF were offered FE-1 testing if they were on pancreatic enzyme replacement therapy (PERT) and on CFTR modulator therapy according to their center's guideline.

Parasites, depredators, and limited resources as potential drivers of winter mortality of feral honeybee colonies in German forests.

Wild honeybees (Apis mellifera) are considered extinct in most parts of Europe. The likely causes of their decline include increased parasite burden, lack of high-quality nesting sites and associated depredation pressure, and food scarcity. In Germany, feral honeybees still colonize managed forests, but their survival rate is too low to maintain viable populations.

Synthesis of Uronic Acid 1-Azasugars as Putative Inhibitors of α-Iduronidase, β-Glucuronidase and Heparanase.

1-Azasugar analogues of l-iduronic acid (l-IdoA) and d-glucuronic acid (d-GlcA) and their corresponding enantiomers have been synthesized as potential pharmacological chaperones for mucopolysaccharidosis I (MPS I), a lysosomal storage disease caused by mutations in the gene encoding α-iduronidase (IDUA). The compounds were efficiently synthesized in nine or ten steps from d- or l-arabinose, and the structures were confirmed by X-ray crystallographic analysis of key intermediates. All compounds were inactive against IDUA, although l-IdoA-configured 8 moderately inhibited β-glucuronidase (β-GLU).

Ventricular septal rupture after delayed STEMI: A modern management approach.

Background: Myocardial infarction associated ventricular septal rupture (VSR) is a potentially catastrophic complication. Though surgical repair remains the definitive treatment, outcomes are poor with high mortality rates.Case and Management: We present the case of a 62-year-old male who presented with a delayed STEMI leading to a VSR and cardiogenic shock.

Development of Improved Synthetic Routes to Pixatimod (PG545), a Sulfated Oligosaccharide-Steroid Conjugate.

The heparan sulfate (HS) mimetic pixatimod (PG545) is a highly potent inhibitor of angiogenesis, tumor growth, and metastasis currently in clinical trials for cancer. PG545 has also demonstrated potent antiviral activity against numerous HS-dependent viruses, including SARS-CoV-2, and shows promise as an antiviral drug for the treatment of COVID-19. Structurally, PG545 consists of a fully sulfated tetrasaccharide conjugated to the steroid 5α-cholestan-3β-ol.

Outcomes With Early Cardiac Catheterization in Out of Hospital Cardiac Arrest Survivors and Utility of a Prognostic Scoring System.

Objectives A retrospective study in patients presenting out of hospital cardiac arrest (OHCA) to assess the impact of early cardiac catheterization on survival and cerebral performance category (CPC) on discharge. Background The role of early coronary angiography in OHCA patients remains controversial. The cardiac arrest hospital prognosis (CAHP) scoring system has not been validated in the US population.

An examination of cardiovascular intensive care unit mortality based on admission day and time.

Background: Recent interest in the 'weekend effect' has been expanded to cardiovascular intensive care units, yet the impact of off-hours admission on mortality and cardiovascular ICU (CICU) length of stay remains uncertain.

Objectives: We examine the association between CICU admission day and time with mortality. Additionally, length-of-stay was also evaluated in relation to admission time.

Temporal Analysis of Tachycardia During Catheter Directed Thrombolysis for Acute Pulmonary Embolism.

Purpose: To evaluate the effect of catheter directed thrombolysis (CDT) on heart rate (HR) in patients with sinus tachycardia and acute pulmonary embolism (PE).

Methods: A retrospective chart review was performed for patients who underwent CDT with tPA for acute massive or submassive PE between 12/2009 and 2/2020. Included were patients who presented with tachycardia at the time of initiation of CDT.

Large-Bore Aspiration Thrombectomy versus Catheter-Directed Thrombolysis for Acute Pulmonary Embolism: A Propensity Score-Matched Comparison.

Purpose: To compare effectiveness and safety of large-bore aspiration thrombectomy (LBAT) with catheter-directed thrombolysis (CDT) for treatment of acute massive and submassive pulmonary embolism (PE).

Materials And Methods: This retrospective review included patients with acute PE treated with LBAT or CDT using tissue plasminogen activator (tPA) between December 2009 and May 2020. A propensity score based on Pulmonary Embolism Severity Index class and PE severity (massive vs submassive) was calculated, and 26 LBAT cases (age 60.

Evaluation of the Benefit of Extended Catheter-Directed Thrombolysis with Serial Angiography for Acute Pulmonary Embolism.

Purpose: To evaluate whether extended catheter-directed thrombolysis (CDT) with repeat visits to the angiography suite provide added benefit in treatment of acute pulmonary embolism (PE).

Materials And Methods: This was a retrospective review of CDT procedures performed for acute PE in 156 patients (age 56.1 y ± 15.

Structural insights into heparanase activity using a fluorogenic heparan sulfate disaccharide.

A synthetic heparan sulfate disaccharide has been assessed as a fluorogenic heparanase substrate, enabling enzyme turnover and inhibition kinetics measurements despite slow turnover. Crystal structures with human heparanase also provide the first ever observation of a substrate in an activated 1S3 conformation, highlighting previously unknown interactions involved in enzymatic processing. Our data provide insights into the heparanase catalytic mechanism, and will inform the design of improved heparanase substrates and inhibitors.

Utilization of an ICU Severity of Illness Scoring System to Triage Patients With ST-Elevation Myocardial Infarction.

Objective: To subjectively identify low-risk ST-elevation myocardial infarction (STEMI) patients and triage this low-risk population to an intermediate level of care.

Background: Many patients with STEMI are admitted to the intensive care unit (ICU), however, a large portion do not merit ICU admission. We sought to examine whether, among post-STEMI patients admitted to the ICU, if an easily obtainable subjective scoring system could predict low-risk patients and safely triage them to an intermediate level of care.

The association between a low critical shoulder angle and SLAP lesions.

Purpose: To evaluate the critical shoulder angle (CSA), acromion index (AI) and further acromion parameters in patients with isolated SLAP lesions compared with patients without SLAP lesions.

Methods: Between 2012 and 2016, the CSA, AI, lateral acromion angle (LAA) and acromion slope (AS) were radiologically examined in consecutive patients > 18 years having had a shoulder arthroscopy with isolated SLAP lesion types II-IV. These were compared to controls without SLAP lesions and without (control group I) or with (control group II) complete supraspinatus tendon (SSP) tears.

Dual targeting of dengue virus virions and NS1 protein with the heparan sulfate mimic PG545.

Dengue virus (DENV) is the most prevalent mosquito-borne flavivirus that infects humans. At present, there are no specific antiviral drugs to treat DENV infection and vaccine development has met with challenges. DENV encodes two glycosaminoglycan (GAG) binding proteins; Envelope (E) and non-structural protein 1 (NS1).

The implementation of an infection prevention bundle reduces surgical site infections following cranial surgery.

Background: The benefit of an infection prevention bundle made up of five basic procedures to avoid surgical site infections (SSIs) following cranial surgery was evaluated.

Methods: Data from all patients with first time elective brain surgery from March 2014 till May 2016 were analyzed. In April 2015, an infection prevention bundle was implemented.

Practice Patterns and In-Hospital Outcomes Associated With Bivalirudin Use Among Patients With Non-ST-Segment-Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention in the United States.

Background: Practice patterns in anticoagulant strategies used during percutaneous coronary intervention (PCI) in the United States for patients with non-ST-segment-elevation myocardial infarction and the comparative outcomes between bivalirudin and unfractionated heparin (UFH) have not been well described.

Methods And Results: Trends in anticoagulant use were examined among 553 562 PCIs performed by 9254 operators at 1538 hospitals for non-ST-segment-elevation myocardial infarction from 2009 to 2014 within the CathPCI Registry. To compare bivalirudin with UFH, propensity score matching and instrumental variable (IV) methods with operator preference for bivalirudin as the instrument were used.