A Pharmacokinetic and Analgesic Efficacy Study of Carprofen in Female CD1 Mice.

The minimization of pain in research animals is a scientific and ethical necessity. Carprofen is commonly used for pain management in mice; however, some data suggest that the standard dosage of 5 mg/kg may not provide adequate analgesia after surgery. We hypothesized that a higher dose of carprofen in mice would reduce pain-associated behaviors and improve analgesia without toxic effects. A pharmacokinetic study was performed in mice given carprofen subcutaneously at 10 or 20 mg/kg. Plasma concentrations were measured at 0.25, 0.5, 1, 2, 4, 8, 12, 24, and 48 h after dosing (n = 3 per time point and treatment). At these doses, plasma levels were above the purported therapeutic level for at least 12 and 24 h, respectively, with respective half-lives of 14.9 and 10.2 h. For the efficacy study, 10 mice per group received anesthesia with or without an ovariectomy. Mice were then given 5 or 10 mg/kg of carprofen, or saline subcutaneously every 12 h. Orbital tightening, arched posture, wound licking, rearing, grooming, nesting behavior, and activity were assessed before surgery and at 4, 8, 12, 24, and 48 h after surgery. The von Frey responses were assessed before and at 4, 12, 24, and 48 h after surgery. The efficacy study showed that all surgery groups had significantly higher scores for orbital tightening, arched posture, and wound licking than did the anesthesia-only groups at 4, 8, 12, and 24-h time points. At the 8 h time point, the surgery groups treated with carprofen had significantly lower arched posture scores than did the surgery group treated with saline only. No significant differences were found between carprofen treatment groups for rearing, grooming, von Frey, activity, or nesting behavior at any time point. These results indicate that subcutaneous carprofen administered at these doses does not provide sufficient analgesia to alleviate postoperative pain in female CD1 mice.

Detecting, Distinguishing, and Spatiotemporally Tracking Photogenerated Charge and Heat at the Nanoscale.

Since dissipative processes are ubiquitous in semiconductors, characterizing how electronic and thermal energy transduce and transport at the nanoscale is vital for understanding and leveraging their fundamental properties. For example, in low-dimensional transition metal dichalcogenides (TMDCs), excess heat generation upon photoexcitation is difficult to avoid since even with modest injected exciton densities exciton-exciton annihilation still occurs. Both heat and photoexcited electronic species imprint transient changes in the optical response of a semiconductor, yet the distinct signatures of each are difficult to disentangle in typical spectra due to overlapping resonances. In response, we employ stroboscopic optical scattering microscopy (stroboSCAT) to simultaneously map both heat and exciton populations in few-layer MoS2 on relevant nanometer and picosecond length- and time scales and with 100-mK temperature sensitivity. We discern excitonic contributions to the signal from heat by combining observations close to and far from exciton resonances, characterizing the photoinduced dynamics for each. Our approach is general and can be applied to any electronic material, including thermoelectrics, where heat and electronic observables spatially interplay, and it will enable direct and quantitative discernment of different types of coexisting energy without recourse to complex models or underlying assumptions.

Zwitterions in 3D Perovskites: Organosulfide-Halide Perovskites.

Although sulfide perovskites usually require high-temperature syntheses, we demonstrate that organosulfides can be used in the milder syntheses of halide perovskites. The zwitterionic organosulfide, cysteamine (CYS; +NH3(CH2)2S-), serves as both the X- site and A+ site in the ABX3 halide perovskites, yielding the first examples of 3D organosulfide-halide perovskites: (CYS)PbX2 (X- = Cl- or Br-). Notably, the band structures of (CYS)PbX2 capture the direct bandgaps and dispersive bands of APbX3 perovskites. The sulfur orbitals compose the top of the valence band in (CYS)PbX2, affording unusually small direct bandgaps of 2.31 and 2.16 eV for X- = Cl- and Br-, respectively, falling in the ideal range for the top absorber in a perovskite-based tandem solar cell. Measurements of the carrier dynamics in (CYS)PbCl2 suggest carrier trapping due to defects or lattice distortions. The highly desirable bandgaps, band dispersion, and improved stability of the organosulfide perovskites demonstrated here motivate the continued expansion and exploration of this new family of materials, particularly with respect to extracting photocurrent. Our strategy of combining the A+ and X- sites with zwitterions may offer more members in this family of mixed-anion 3D hybrid perovskites.

Recurrent sudden cardiac death secondary to anomalous right coronary artery: Insights into prevalence and management.

A 32-year-old woman presented after ventricular fibrillation arrest requiring three defibrillations. The episode coincided with an upper respiratory infection and physical exertion. Eight years prior, she survived another cardiac arrest of unknown cause during childbirth. This time, imaging revealed an anomalous right coronary artery connecting to the left coronary cusp, with a small, slit-like osteal orifice coursing between the aorta and pulmonary artery. Surgical exploration revealed an intramural segment of the right coronary artery, which was surgically unroofed with improvement in cardiac function. An implantable cardioverter-defibrillator was implanted for secondary prevention of sudden cardiac death. Surgery is recommended for malignant anomalous coronary arteries, with a very low risk of recurrence of arrhythmia and sudden cardiac death after surgery. However, with growing evidence for persistent risk of arrhythmia and sudden cardiac death even after surgical correction of the anomalous coronary arteries, more experts choose to take secondary prevention measures as a component of initial management.

Tmc proteins are essential for zebrafish hearing where Tmc1 is not obligatory.

Perception of sound is initiated by mechanically gated ion channels at the tips of stereocilia. Mature mammalian auditory hair cells require transmembrane channel-like 1 (TMC1) for mechanotransduction, and mutations of the cognate genetic sequences result in dominant or recessive heritable deafness forms in humans and mice. In contrast, zebrafish lateral line hair cells, which detect water motion, require Tmc2a and Tmc2b. Here, we use standard and multiplex genome editing in conjunction with functional and behavioral assays to determine the reliance of zebrafish hearing and vestibular organs on Tmc proteins. Surprisingly, our approach using multiple mutant alleles demonstrates that hearing in zebrafish is not dependent on Tmc1, nor is it fully dependent on Tmc2a and Tmc2b. Hearing however is absent in triple-mutant zebrafish that lack Tmc1, Tmc2a and Tmc2b. These outcomes reveal a striking resemblance of Tmc protein reliance in the vestibular sensory epithelia of mammals to the maculae of zebrafish. Moreover, our findings disclose a logic of Tmc use where hearing depends on a complement of Tmc proteins beyond those employed to sense water motion.

Imaging material functionality through three-dimensional nanoscale tracking of energy flow.

The ability of energy carriers to move between atoms and molecules underlies biochemical and material function. Understanding and controlling energy flow, however, requires observing it on ultrasmall and ultrafast spatio-temporal scales, where energetic and structural roadblocks dictate the fate of energy carriers. Here, we developed a non-invasive optical scheme that leverages non-resonant interferometric scattering to track tiny changes in material polarizability created by energy carriers. We thus map evolving energy carrier distributions in four dimensions of spacetime with few-nanometre lateral precision and directly correlate them with material morphology. We visualize exciton, charge and heat transport in polyacene, silicon and perovskite semiconductors and elucidate how disorder affects energy flow in three dimensions. For example, we show that morphological boundaries in polycrystalline metal halide perovskites possess lateral- and depth-dependent resistivities, blocking lateral transport for surface but not bulk carriers. We also reveal strategies for interpreting energy transport in disordered environments that will direct the design of defect-tolerant materials for the semiconductor industry of tomorrow.

Associations of Sitting Behavior Patterns With Cardiometabolic Risk in Children: The Sit Less for Health Cross-Sectional Study.

BACKGROUND: The objective of this study was to investigate the associations between sedentary behavior patterns and cardiometabolic risk in children using a monitor that accurately distinguishes between different postures. METHODS: In this cross-sectional study, 118 children (67 girls) aged 11-12 years had adiposity, blood pressure, lipids, and glucose measured, and then they wore an activPAL device to record sitting, standing, and stepping for 7 consecutive days. Data were analyzed using multiple linear regression. RESULTS: After adjustment for potential confounders and moderate to vigorous physical activity, the number of breaks in sitting was significantly negatively associated with adiposity (standardized ß ≥ -0.546; P ≤ .001) and significantly positively associated with high-density lipoprotein cholesterol (ß = 0.415; P ≤ .01). Time in prolonged sitting bouts was significantly negatively associated with adiposity (ß ≥ -0.577; P ≤ .001) and significantly positively associated with high-density lipoprotein cholesterol (ß = 0.432; P ≤ .05). Standing time was significantly negatively associated with adiposity (ß ≥ -0.270; P ≤ .05) and significantly positively associated with high-density lipoprotein cholesterol (ß = 0.312; P ≤ .05). CONCLUSIONS: This study suggests that increasing the number of breaks in sitting and increasing standing time are beneficially associated with cardiometabolic risk and should be considered in health promotion interventions in children.