Search

Our lab has developed a new series of self-immolative MR agents for the rapid detection of enzyme activity in mouse models expressing β-galactosidase (β-gal). We investigated two molecular architectures to create agents that detect β-gal activity by modulating the coordination of water to Gd III . The first is an intermolecular approach, wherein we designed several structural isomers to maximize coordination of endogenous carbonate ions. The second involves an intramolecular mechanism for q modulation. We incorporated a pendant coordinating carboxylate ligand with a 2, 4, 6, or 8 carbon linker to saturate ligand coordination to the Gd III ion. This renders the agent ineffective. We show that one agent in particular (6-C pendant carboxylate) is an extremely effective MR reporter for the detection of enzyme activity in a mouse model expressing β-gal., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Dipotassio-9-germafluorenyl dianion (3b) was synthesized by reduction of 9,9-dichloro-9-germafluorene (4b) with sodium/potassium alloy in tetrahydrofuran. The X-ray crystal structure of 3b, like that for the analogous silicon compound 3a, shows C-C bond length equalization in the five-membered metallole rings and C-C bond length alternation in the six-membered benzenoid rings, indicating aromatic delocalization of electrons into the germole ring of 3b. Calculated nucleus independent chemical shift (NICS) values indicate that the five-membered ring is more aromatic than the six-membered rings in 3a and 3b. Derivatization of 3b with Me(3)SiCl gave 9,9-bis(trimethylsilyl)-9-germafluorene (5). Controlled oxidation of 3b yielded dipotassio-9,9'-digerma-9,9'-bifluorenyl dianion (6). Reaction of 6 with MeOH yielded 9,9'-digerma-9,9'-bifluorene (7). The X-ray structure of 6 indicates C-C bond length alternation in the five-membered rings. Thus dianion 6, like its silicon analogue 8, has the negative charges localized at metal atoms and no aromatic character. Dipotassio-9,9'-bifluorenyl dianion (9), the carbon analogue of 6, exhibits aromaticity with its X-ray crystal structure showing the C-C bond length equalization in both the five- and six-membered rings. Derivatization of 9 with MeI gave 9,9'-dimethyl-9,9'-bifluorene (10). The structure of 10 shows that the two fluorenyl rings are cis to each other with a torsional angle of 59 degrees and a long C-C single bond (1.60 A) connecting them.

1-Silafluorene dianion was synthesized by potassium reduction of 1,1-dichloro-1-silafluorene in refluxing THF. The X-ray structure of 1,1-dipotassio-1-silafluorene (3b) shows C-C bond length equalization in the five-membered silole ring and C-C bond length alternation in the six-membered benzene rings, indicating aromatic delocalization of electrons in the silole ring. The downfield (29)Si chemical shift at 29.0 ppm and theoretical calculations also support electron delocalization in the silole ring of 3b. Dianion salt 3b underwent nucleophilic reactions with Me(3)SiCl and EtBr to form the corresponding disubstituted products. Benzaldehyde underwent reductive coupling in the presence of 3b. Slow oxidation of 3b yielded 1,1'-dipotassio-1,1'-bis(silafluorene) (16). The X-ray structure and (29)Si chemical shift (-38.0 ppm) of 16 indicate localized negative charges at the silicon atoms and no aromatic character. Heating a DME/hexane solution of 3b in the presence of 18-crown-6 led to a novel diradical dianion salt.

Intensive care nursery personnel increasingly seek to practice developmental and family-centered care, but become frustrated when attempting implementation. Reports of effective change strategies for integration to practice are limited. This article presents a summary of one unit's experience using the performance improvement process to move toward a developmentally supportive, family-centered care delivery model. Results to date indicate that a comprehensive quality improvement process guided by a unit-based newborn developmental specialist can provide the framework to achieve the change from traditional, provider-centered, task-directed care to holistic, individualized, relationship-based care.

There is increasing concern that environmental stimuli in the Neonatal Intensive Care Unit (NICU) may be detrimental to the preterm infants hospitalized there. Separately, there is longstanding recognition that preterm infants at 40 weeks postconceptional age habituate less reliably than full-term infants. This study uses a relevant animal model to test whether exposure to NICU sounds, as a single departure from normal neonatal experience, can alter habituation. Chicks were incubated, hatched, and reared in either a quiet or a NICU-sound environment. Habituation was measured by the length of time that chicks delay their ongoing peeping upon hearing a white noise stimulus. NICU-sound-reared 4-day-olds failed to habituate, showing as much responsiveness at the end of repeated stimulation as at the beginning. This is, to our knowledge, the first demonstration that atypical sound exposure alone can alter this fundamental aspect of neurosensory competence in an otherwise healty neonate.

Seizures in the newborn are different from those occurring in older children and adults. Health care professionals may find it difficult to recognize neonatal seizures because of their sometimes subtle manifestations. Convulsive behavior has many etiologies; some are associated with a favorable and some with a poor prognosis. Treatment protocol is controversial because both the seizures themselves and the drugs used to treat them may damage the immature brain. The high mortality and morbidity rates of infants who experience seizures make it imperative that the neonatal seizure be recognized, its etiology diagnosed, and treatment begun promptly.