Enantioselective Vanadium-Catalyzed Oxidative Coupling: Development and Mechanistic Insights.

The evolution of a more reactive chiral vanadium catalyst for enantioselective oxidative coupling of phenols is reported, ultimately resulting in a simple monomeric vanadium species combined with a Brønsted or Lewis acid additive. The resultant vanadium complex is found to effect the asymmetric oxidative ortho-ortho coupling of simple phenols and 2-hydroxycarbazoles with good to excellent levels of enantioselectivity. Experimental and quantum mechanical studies of the mechanism indicate that the additives aggregate the vanadium monomers. In addition, a singlet to triplet crossover is implicated prior to carbon-carbon bond formation. The two lowest energy diastereomeric transition states leading to the enantiomeric products differ substantially with the path to the minor enantiomer involving greater torsional strain between the two phenol moieties.

Pregnancy-Onset Ulcerative Colitis in a Pediatric Patient Presenting With Altered Mental Status and Severe Anemia.

Ulcerative colitis (UC) classically presents with abdominal pain, hematochezia, or diarrhea. However, it can present atypically in pediatric and pregnant patients, posing a diagnostic challenge. A healthy, 16-year-old primigravida presented at 18 weeks and six days of gestation with sudden-onset altered mental status and severe anemia. Hematochezia began about 12 hours after admission. She underwent extensive workup, leading to an endoscopic and histopathologic diagnosis of UC, and achieved prenatal remission with high-dose steroids and infliximab. Her pregnancy, however, was complicated by severe preeclampsia, and her child's post-delivery course was medically complex from an unrelated etiology. Pregnancy-onset inflammatory bowel disease (IBD) in the pediatric population is an uncommon but important consideration. Early diagnosis, treatment, and counseling are vital to achieve results comparable to those of patients without IBD.

Rapid vascular glucose uptake via enzyme-assisted subcutaneous infusion: enzyme-assisted subcutaneous infusion access study.

BACKGROUND: Enzyme-assisted subcutaneous infusion (EASI), with subcutaneous human recombinant hyaluronidase pretreatment, may offer an alternative to standard intravenous (IV) access. OBJECTIVES: This study's objectives were to assess paramedic (Emergency Medical Technician-Paramedic [EMTP])-placed EASI access in volunteers to determine (1) feasibility of EMTP EASI access placement; (2) subject/EMTP ratings of placement ease, discomfort, and overall EASI vs IV preference; and (3) speed of intravascular uptake of EASI infusate. METHODS: Twenty adults underwent 20-gauge IV placement by 4 EMTPs, receiving a 250-mL maximal-rate IV bolus of normal saline. Next, each subject received in the other arm a 20-gauge EASI access line (with 1-mL injection of 150 U of human recombinant hyaluronidase), through which was infused 250 mL D5NS (1 g glucose was labeled with stable tracer 13C). Blood draws enabled gas chromatography/mass spectrometry (GC/MS) assessment of 13C-glucose uptake. Intravenous access and EASI access were compared for time parameters and subject/EMTP ratings. Data were analyzed with median and interquartile range, Kruskal-Wallis testing, Fisher exact test, and regression (GC/MS data). RESULTS: Intravenous access and EASI access were successful in all 20 subjects. Compared with EASI access (all placed in <15 seconds), IV access took longer; but the 250-mL bolus was given more quickly via IV access. EMTPs rated EASI easier to place than IV; pain ratings were similar for IV and EASI. The GC/MS showed intravascular uptake at all time points. CONCLUSIONS: Enzyme-assisted subcutaneous infusion is faster and easier to initiate than IV access; intravascular absorption of EASI-administered fluids begins within minutes.

Does Size Matter When Calculating the "Correct" Tidal Volume for Pediatric Mechanical Ventilation?: A Hypothesis Based on FVC.

BACKGROUND: Tidal volumes standardized to predicted body weight are recommended for adult mechanical ventilation, but children are frequently ventilated by using measured body weight. The goal of this study was to examine the difference in FVC (in milliliters per kilogram [mL/kg]) by using measured body weight compared with predicted body weight in children. METHODS: This retrospective analysis included outpatient pulmonary function tests (PFTs) from two datasets. Dataset one included 6- to 19-year-old patients undergoing PFTs from the nationally representative Canadian Health Measures Survey. Dataset two included 6- to 20-year-old patients undergoing PFTs at a freestanding children's hospital. FVC mL/kg values were analyzed against BMI z scores to show changes in FVC vs BMI between measured and predicted weight. RESULTS: Dataset one included 5,394 PFTs from the Canadian survey. FVC from measured weight decreased as the BMI z score group increased. The median FVC from measured weight was 81.4 mL/kg in the lowest BMI z score group and 51.7 mL/kg in the highest BMI z score group. FVC from predicted weight increased slightly with increasing BMI z score group. Dataset two included 8,472 patient PFTs from clinical measurement. A decline in median FVC from measured weight (from 69.4 to 37.6 mL/kg) as BMI z score group increased was also seen. CONCLUSIONS: FVC differs significantly when standardizing to measured weight vs predicted weight. Obese children have lung volumes reflecting their predicted body weight from height. Children with low or normal BMI have lung volumes reflecting measured body weight. These findings suggest that targeting tidal volume by using the lower of measured and predicted body weights would be the most lung-protective strategy.

Immunofluorescent detection of two thymidine analogues (CldU and IdU) in primary tissue.

Accurate measurement of cell division is a fundamental challenge in experimental biology that becomes increasingly complex when slowly dividing cells are analyzed. Established methods to detect cell division include direct visualization by continuous microscopy in cell culture, dilution of vital dyes such as carboxyfluorescein di-aetate succinimidyl ester (CFSE), immuno-detection of mitogenic antigens such as ki67 or PCNA, and thymidine analogues. Thymidine analogues can be detected by a variety of methods including radio-detection for tritiated thymidine, immuno-detection for bromo-deoxyuridine (BrdU), chloro-deoxyuridine (CldU) and iodo-deoxyuridine (IdU), and chemical detection for ethinyl-deoxyuridine (EdU). We have derived a strategy to detect sequential incorporation of different thymidine analogues (CldU and IdU) into tissues of adult mice. Our method allows investigators to accurately quantify two successive rounds of cell division. By optimizing immunostaining protocols our approach can detect very low dose thymidine analogues administered via the drinking water, safe to administer to mice for prolonged periods of time. Consequently, our technique can be used to detect cell turnover in very long-lived tissues. Optimal immunofluoresent staining results can be achieved in multiple tissue types, including pancreas, skin, gut, liver, adrenal, testis, ovary, thyroid, lymph node, and brain. We have also applied this technique to identify oncogenic transformation within tissues. We have further applied this technique to determine if transit-amplifying cells contribute to growth or renewal of tissues. In this sense, sequential administration of thymidine analogues represents a novel approach for studying the origins and survival of cells involved in tissue homeostasis.