Low Motor Dexterity and Significant Behaviors Following Hospitalized Isolation in Children.

The main objective of this study was to describe the cortical patterns of brain activity during a gross dexterity task and develop a behavioral profile of children experiencing isolation. A cross-sectional assessment was conducted during one visit. Sample: Four pediatric patients who had undergone isolation within a hospital comprised the full data collection. During the collection, participants completed the Box and Blocks Test of gross manual dexterity while undergoing imaging of the motor cortex using functional near-infrared spectroscopy. Participants also completed a Behavioral Assessment System for Children, Third Edition (BASC-3) self-report, which was analyzed along with a parent report to quantify their emotional and social behaviors. All participants displayed lower gross dexterity levels than normative data. Furthermore, three out of the four participants displayed ipsilateral dominance of the motor cortex during the dexterity task. Three of the participants displayed behavioral measures reported within clinically significant or at-risk scores. Clinically significant behavioral scores coupled with lower than expected manual dexterity values and ipsilateral hemispheric dominance indicate that neuroplastic changes can occur in populations undergoing hospitalized isolation. While the impacts of the treatments and isolation in this case cannot be separated, further studies should be conducted to understand these impacts of isolation.

Breaking Symmetry: Engineering Single-Chain Dimeric Streptavidin as Host for Artificial Metalloenzymes.

The biotin-streptavidin technology has been extensively exploited to engineer artificial metalloenzymes (ArMs) that catalyze a dozen different reactions. Despite its versatility, the homotetrameric nature of streptavidin (Sav) and the noncooperative binding of biotinylated cofactors impose two limitations on the genetic optimization of ArMs: (i) point mutations are reflected in all four subunits of Sav, and (ii) the noncooperative binding of biotinylated cofactors to Sav may lead to an erosion in the catalytic performance, depending on the cofactor:biotin-binding site ratio. To address these challenges, we report on our efforts to engineer a (monovalent) single-chain dimeric streptavidin (scdSav) as scaffold for Sav-based ArMs. The versatility of scdSav as host protein is highlighted for the asymmetric transfer hydrogenation of prochiral imines using [Cp*Ir(biot-p-L)Cl] as cofactor. By capitalizing on a more precise genetic fine-tuning of the biotin-binding vestibule, unrivaled levels of activity and selectivity were achieved for the reduction of challenging prochiral imines. Comparison of the saturation kinetic data and X-ray structures of [Cp*Ir(biot-p-L)Cl]·scdSav with a structurally related [Cp*Ir(biot-p-L)Cl]·monovalent scdSav highlights the advantages of the presence of a single biotinylated cofactor precisely localized within the biotin-binding vestibule of the monovalent scdSav. The practicality of scdSav-based ArMs was illustrated for the reduction of the salsolidine precursor (500 mM) to afford (R)-salsolidine in 90% ee and >17 000 TONs. Monovalent scdSav thus provides a versatile scaffold to evolve more efficient ArMs for in vivo catalysis and large-scale applications.

Comparative Noninvasive Measurement of Cardiac Output Based on the Inert Gas Rebreathing Method (Innocor®) and MRI in Patients with Univentricular Hearts.

There are many complex cardiac malformations that are characterized by a functionally univentricular physiology. Staged surgical repair according to the Fontan principle separates the systemic and pulmonary circulations by connecting the systemic venous return to the pulmonary arteries. However, long-term follow-up studies demonstrate a gradual deterioration of cardiac function, particularly from the second or third decade. Noninvasive evaluation of the cardiac function is, therefore, important in the follow-up of these patients. The cardiac index (CI) is a reliable hemodynamic parameter and represents an important marker of cardiac function. We compared CI values determined by cardiac MRI (CMRI) with values obtained by noninvasive inert gas rebreathing (IGR; Innocor® system). Sixteen patients (age range: 7.2-32.7 years) with functionally univentricular hearts (UVH) following total cavopulmonary connection (TCPC) were compared with 12 healthy subjects (age range: 8.5-18.6 years). The standard treadmill protocol of the German Society of Pediatric Cardiology was used for exercise testing. CI was determined at rest and at two standardized submaximal exercise levels. In all subjects, CI increased under exercise conditions, but the values were significantly lower in patients with UVH. There was no significant difference between patients with UVH and predominantly right- or left-ventricular morphology. In comparison with CMRI measurements, the CI values obtained by the IGR method tended to be lower, with a mean difference of 1.02 l/min/m2. Noninvasive measurement of CI with the IGR method is feasible at rest and during exercise, and appears to be suited for routine determination of CI in patients with UVH following TCPC.

Oxidative Decarboxylation of Short-Chain Fatty Acids to 1-Alkenes.

The enzymatic oxidative decarboxylation of linear short-chain fatty acids (C4:0-C9:0) employing the P450 monooxygenase OleT, O2 as the oxidant, and NAD(P)H as the electron donor gave the corresponding terminal C3 to C8  alkenes with product titers of up to 0.93 g L(-1) and TTNs of >2000. Key to this process was the construction of an efficient electron-transfer chain employing putidaredoxin CamAB in combination with NAD(P)H recycling at the expense of glucose, formate, or phosphite. This system allows for the biocatalytic production of industrially important 1-alkenes, such as propene and 1-octene, from renewable resources for the first time.