Author Correction: Leveraging excited-state coherence for synthetic control of ultrafast dynamics.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Leveraging excited-state coherence for synthetic control of ultrafast dynamics.

Design-specific control over excited-state dynamics is necessary for any application seeking to convert light into chemical potential. Such control is especially desirable in iron(II)-based chromophores, which are an Earth-abundant option for a wide range of photo-induced electron-transfer applications including solar energy conversion1 and catalysis2. However, the sub-200-femtosecond lifetimes of the redox-active metal-to-ligand charge transfer (MLCT) excited states typically encountered in these compounds have largely precluded their widespread use3. Here we show that the MLCT lifetime of an iron(II) complex can be manipulated using information from excited-state quantum coherences as a guide to implementing synthetic modifications that can disrupt the reaction coordinate associated with MLCT decay. We developed a structurally tunable molecular platform in which vibronic coherences-that is, coherences reflecting a coupling of vibrational and electronic degrees of freedom-were observed in ultrafast time-resolved absorption measurements after MLCT excitation of the molecule. Following visualization of the vibrational modes associated with these coherences, we synthetically modified an iron(II) chromophore to interfere with these specific atomic motions. The redesigned compound exhibits a MLCT lifetime that is more than a factor of 20 longer than that of the parent compound, indicating that the structural modification at least partially decoupled these degrees of freedom from the population dynamics associated with the electronic-state evolution of the system. These results demonstrate that using excited-state coherence data may be used to tailor ultrafast excited-state dynamics through targeted synthetic design.

The impact of clinical placement site, community clinic versus tertiary hospital, on midwifery students' clinical learning experience in Sierra Leone: a cohort study.

BACKGROUND: In midwifery education, the clinical learning experience (CLE) is a critical component to gaining competency and should comprise greater than 50% of a student's education. Many studies have identified positive and negative factors affecting students' CLE. However, few studies have directly compared the difference in CLE based on placement at a community clinic versus a tertiary hospital. METHODS: The aim of this study was to examine how clinical placement site, clinic or hospital, impacts students' CLE in Sierra Leone. A once 34-question survey was given to midwifery students attending one of four public midwifery schools in Sierra Leone. Median scores were compared for survey items by placement site using Wilcoxon tests. The relationship between clinical placement and student's experience were assessed using multilevel logistic regression. RESULTS: Two-hundred students (hospitals students = 145 (72.5%); clinic students = 55 (27.5%) across Sierra Leone completed surveys. Most students (76%, n = 151) reported satisfaction with their clinical placement. Students placed at clinics were more satisfied with opportunities to practice/develop skills (p = 0.007) and more strongly agreed preceptors treated them with respect (p = 0.001), helped improve their skills (p = 0.001), provided a safe environment to ask questions (p = 0.002), and had stronger teaching/mentorship skills (p = 0.009) than hospital students. Students placed at hospitals had greater satisfaction in exposure to certain clinical opportunities including completing partographs (p < 0.001); perineal suturing (p < 0.001); drug calculations/administration (p < 0.001) and estimation of blood loss (p = 0.004) compared to clinic students. The odds of students spending more than 4 h per day in direct clinical care were 5.841 (95% CI: 2.187-15.602) times higher for clinic students versus hospital students. There was no difference between clinical placement sites in regards to number of births students attended (OR 0.903; 95% CI: 0.399, 2.047) or number of births students managed without a preceptor/clinician present (OR 0.729; 95% CI: 0.285, 1.867). CONCLUSION: The clinical placement site, hospital or clinic, impacts midwifery students' CLE. Clinics offered students significantly greater attributes of a supportive learning environment and access to direct, hands-on opportunities for patient care. These findings may be helpful for schools when using limited resources to improve the quality of midwifery education.

Oxidizing Americium(III) with Sodium Bismuthate in Acidic Aqueous Solutions.

Historic perspectives describing f-elements as being redox "inactive" are fading. Researchers continue to discover new oxidation states that are not as inaccessible as once assumed for actinides and lanthanides. Inspired by those contributions, we studied americium(III) oxidation in aqueous media under air using NaBiO3(s). We identified selective oxidation of Am3+(aq) to AmO22+(aq) or AmO21+(aq) could be achieved by changing the aqueous matrix identity. AmO22+(aq) formed in H3PO4(aq) (1 M) and AmO21+(aq) formed in dilute HCl(aq) (0.1 M). These americyl products were stable for weeks in solution. Also included is a method to recover 243Am from the americium and bismuth mixtures generated during these studies.

Advancing the Am Extractant Design through the Interplay among Planarity, Preorganization, and Substitution Effects.

Advancing the field of chemical separations is important for nearly every area of science and technology. Some of the most challenging separations are associated with the americium ion Am(III) for its extraction in the nuclear fuel cycle, 241Am production for industrial usage, and environmental cleanup efforts. Herein, we study a series of extractants, using first-principle calculations, to identify the electronic properties that preferentially influence Am(III) binding in separations. As the most used extractant family and because it affords a high degree of functionalization, the polypyridyl family of extractants is chosen to study the effects of the planarity of the structure, preorganization of coordinating atoms, and substitution of various functional groups. The actinyl ions are used as a structurally simplified surrogate model to quickly screen the most promising candidates that can separate these metal ions. The down-selected extractants are then tested for the Am(III)/Eu(III) system. Our results show that π interactions, especially those between the central terpyridine ring and Am(III), play a crucial role in separation. Adding an electron-donating group onto the terpyridine backbone increases the binding energies to Am(III) and stabilizes Am-terpyridine coordination. Increasing the planarity of the extractant increases the binding strength as well, although this effect is found to be rather weak. Preorganizing the coordinating atoms of an extractant to their binding configuration as in the bound metal complex speeds up the binding process and significantly improves the kinetics of the separation process. This conclusion is validated by the synthesized 1,2-dihydrodipyrido[4,3-b;5,6-b]acridine (13) extractant, a preorganized derivative of the terpyridine extractant, which we experimentally showed was four times more effective than terpyridine at separating Am3+ from Eu3+ (SFAm/Eu ∼ 23 ± 1).

Mapping retinal ganglion cell somas in a large-eyed glaucoma model.

Purpose: The purpose of this study was to identify a robust, representative region of interest (ROI) for studies of retinal ganglion cell (RGC) soma loss in feline congenital glaucoma (FCG), a spontaneous, large-eyed glaucoma model. Methods: Seven FCG and three wild-type (wt) eyes were collected from 10 adult cats of both sexes. Eyes enucleated postmortem were immediately fixed overnight in 4% paraformaldehyde and then stored in 0.1 M PBS at 4 °C. The retinas were wholemounted, Nissl stained with cresyl violet, and imaged using light microscopy. Somas of RGCs were manually identified according to long-established morphological criteria and quantified using a semiautomated method; their coordinates were used to create density maps and plots of the retinal topography. The RGC axon counts for the corresponding eyes were obtained from glutaraldehyde-fixed, resin-embedded optic nerve cross-sections stained with 0.1% p-phenylenediamine (PPD) using a semiautomated counting method. Correlations between total optic nerve axons and RGC soma counts were assessed by linear regression. A k-means cluster algorithm was used to identify a retinal ROI, with further definition using a probability density algorithm. Results: Interindividual variability in RGC total soma counts was more pronounced in FCG cats (mean = 83,244, range: 0-155,074) than in wt cats (mean = 117,045, range: 97,373-132,972). In general, RGC soma counts were lower in FCG cats than they were in wt cats. RGC axon counts in the optic nerve cross-sections were lower than, but strongly correlated to, the total RGC soma count across all cats (in wt and FCG retinas; R2 = 0.88) and solely FCG eyes (R2 = 0.92). The k-means cluster algorithm indicated a region of the greatest mean difference between the normal wt retinas and FCG-affected retinas within the temporal retina, incorporating the region of the area centralis. Conclusions: As in other species, RGC soma count and topography are heterogeneous between individual cats, but we identified an ROI in the temporal retina for future studies of RGC soma loss or preservation in a large-eyed model of congenital glaucoma. Many of the methods refined and established to facilitate studies in this FCG model will be broadly applicable to studies in other large-eyed models.

The post-natal development of intraocular pressure in normal domestic cats (Felis catus) and in feline congenital glaucoma.

Intraocular pressure (IOP) is the most consistent risk factor for progressive vision loss in glaucoma. Cats with recessively inherited feline congenital glaucoma (FCG) exhibit elevated IOP with gradual, painless progression of glaucoma similar to humans and are studied as a model of glaucoma in humans and animals. Here, post-natal development of IOP was characterized in normal domestic cats and in cats with FCG caused by a homozygous LTBP2 mutation. Rebound tonometry (TonoVet®, ICare Oy, Finland) was used to measure IOP non-invasively, 2-3 times weekly in 63 FCG and 33 normal kittens, of both sexes, from eyelid opening until 3-6 months of age. IOPs in the left and right eyes of both FCG and normal kittens were compared by paired t-test and linear regression. One-way ANOVA and Tukey-Kramer post-tests were used to compare IOP of cats grouped by age and disease status. A p-value <0.05 was considered significant. In the second week of life, mean IOP was 7.16 mmHg (SD = 1.3) in normal kittens and 8.72 mmHg (SD = 1.4) in kittens with FCG. Mean IOP at age 10 weeks was significantly higher in FCG (19.8 mmHg; 95% CI = 17.7, 21.9  mmHg) than in normal kittens (13.2 mmHg; 95% CI = 11.9, 14.5  mmHg). At 3 months of age, IOP in normal cats reached adult values while IOP in FCG cats continued to increase through at least six months of age. These results provide ranges for normal IOP values in young kittens and confirm that IOP is significantly higher than normal by 10wks of age in this spontaneous feline glaucoma model.

SCN5A variant that blocks fibroblast growth factor homologous factor regulation causes human arrhythmia.

Nav channels are essential for metazoan membrane depolarization, and Nav channel dysfunction is directly linked with epilepsy, ataxia, pain, arrhythmia, myotonia, and irritable bowel syndrome. Human Nav channelopathies are primarily caused by variants that directly affect Nav channel permeability or gating. However, a new class of human Nav channelopathies has emerged based on channel variants that alter regulation by intracellular signaling or cytoskeletal proteins. Fibroblast growth factor homologous factors (FHFs) are a family of intracellular signaling proteins linked with Nav channel regulation in neurons and myocytes. However, to date, there is surprisingly little evidence linking Nav channel gene variants with FHFs and human disease. Here, we provide, to our knowledge, the first evidence that mutations in SCN5A (encodes primary cardiac Nav channel Nav1.5) that alter FHF binding result in human cardiovascular disease. We describe a five*generation kindred with a history of atrial and ventricular arrhythmias, cardiac arrest, and sudden cardiac death. Affected family members harbor a novel SCN5A variant resulting in p.H1849R. p.H1849R is localized in the central binding core on Nav1.5 for FHFs. Consistent with these data, Nav1.5 p.H1849R affected interaction with FHFs. Further, electrophysiological analysis identified Nav1.5 p.H1849R as a gain-of-function for INa by altering steady-state inactivation and slowing the rate of Nav1.5 inactivation. In line with these data and consistent with human cardiac phenotypes, myocytes expressing Nav1.5 p.H1849R displayed prolonged action potential duration and arrhythmogenic afterdepolarizations. Together, these findings identify a previously unexplored mechanism for human Nav channelopathy based on altered Nav1.5 association with FHF proteins.

Advances in heavy alkaline earth chemistry provide insight into complexation of weakly polarizing Ra2+, Ba2+, and Sr2+ cations.

Numerous technologies-with catalytic, therapeutic, and diagnostic applications-would benefit from improved chelation strategies for heavy alkaline earth elements: Ra2+, Ba2+, and Sr2+. Unfortunately, chelating these metals is challenging because of their large size and weak polarizing power. We found 18-crown-6-tetracarboxylic acid (H4COCO) bound Ra2+, Ba2+, and Sr2+ to form M(HxCOCO)x-2. Upon isolating radioactive 223Ra from its parent radionuclides (227Ac and 227Th), 223Ra2+ reacted with the fully deprotonated COCO4- chelator to generate Ra(COCO)2-(aq) (log KRa(COCO)2- = 5.97 ± 0.01), a rare example of a molecular radium complex. Comparative analyses with Sr2+ and Ba2+ congeners informed on what attributes engendered success in heavy alkaline earth complexation. Chelators with high negative charge [-4 for Ra(COCO)2-(aq)] and many donor atoms [≥11 in Ra(COCO)2-(aq)] provided a framework for stable complex formation. These conditions achieved steric saturation and overcame the weak polarization powers associated with these large dicationic metals.

A Sierra Leone 2021 Midwifery Clinical Training Needs Assessment: A Call to Action to Augment Clinical Precepting.

Objective: Sierra Leone has one of the highest maternal mortality and infant mortality rates globally. We share findings from a Midwifery Clinical Training Needs Assessment, conducted in 2021 as a collaboration between the Government of Sierra Leone and Seed Global Health. The assessment identified existing needs and gaps in midwifery clinical training at health facilities in Sierra Leone from various stakeholders' perspectives. Methods: The descriptive needs assessment utilized mixed methods, including surveys, focus group discussions (FGDs), interviews, and reviews of maternal medical records. Results: The following showed needs and gaps in labor and delivery management; record keeping; triage processes; clinical education for students, recent graduates, and preceptors; and lack of infrastructure and resources. Conclusion: The knowledge gained from this needs assessment can further the development of midwifery clinical training programs in Sierra Leone and other low-income countries facing similar challenges. We discuss the implication of our findings.

Antimicrobial Peptide Expression at the Ocular Surface and Their Therapeutic Use in the Treatment of Microbial Keratitis.

Microbial keratitis is a common cause of ocular pain and visual impairment worldwide. The ocular surface has a relatively paucicellular microbial community, mostly found in the conjunctiva, while the cornea would be considered relatively sterile. However, in patients with microbial keratitis, the cornea can be infected with multiple pathogens including Staphylococcus aureus, Pseudomonas aeruginosa, and Fusarium sp. Treatment with topical antimicrobials serves as the standard of care for microbial keratitis, however, due to high rates of pathogen resistance to current antimicrobial medications, alternative therapeutic strategies must be developed. Multiple studies have characterized the expression and activity of antimicrobial peptides (AMPs), endogenous peptides with key antimicrobial and wound healing properties, on the ocular surface. Recent studies and clinical trials provide promise for the use of AMPs as therapeutic agents. This article reviews the repertoire of AMPs expressed at the ocular surface, how expression of these AMPs can be modulated, and the potential for harnessing the AMPs as potential therapeutics for patients with microbial keratitis.

Predictors of postabortion contraception use in Cambodia.

OBJECTIVE: To evaluate which characteristics collected at the point of abortion are associated with contraceptive use over the extended postabortion period for women in Cambodia. METHODS: The study includes a cohort of 500 women who attended a Marie Stopes International Cambodia clinic for an induced abortion. The primary outcomes are use of effective contraception ≥80% of the time over the 4- and 12-month period postabortion. We conducted a bivariate analysis to assess the association between each characteristic and the outcome, followed by multivariable modeling to identify the strongest predictors of the outcomes. RESULTS: Nearly 44% of the women used contraception for more than 80% of the time during both follow-up periods. Several sociodemographic and reproductive factors were crudely associated with the outcomes. In the multivariable model, prior use of contraception, intention to use postabortion contraception, increased number of children and medical abortion were associated with increased contraceptive use over the year postabortion. Occupation was a predictor at 4 months only, and abortion method was a predictor at 12 months only. CONCLUSIONS: The models were satisfactory in predicting the outcome of contraceptive continuation both at 4 and 12 months. The paper sets out a methodology for modeling these predictors that can help inform more client-centered counseling and services for women. IMPLICATIONS: Factors known when attending a clinic for induced abortion can help inform more targeted and client-centered postabortion family planning counseling and services for women in Cambodia.

Insights into the excited state dynamics of Fe(ii) polypyridyl complexes from variable-temperature ultrafast spectroscopy.

In an effort to better define the nature of the nuclear coordinate associated with excited state dynamics in first-row transition metal-based chromophores, variable-temperature ultrafast time-resolved absorption spectroscopy has been used to determine activation parameters associated with ground state recovery dynamics in a series of low-spin Fe(ii) polypyridyl complexes. Our results establish that high-spin (5T2) to low-spin (1A1) conversion in complexes of the form [Fe(4,4'-di-R-2,2'-bpy')3]2+ (R = H, CH3, or tert-butyl) is characterized by a small but nevertheless non-zero barrier in the range of 300-350 cm-1 in fluid CH3CN solution, a value that more than doubles to ∼750 cm-1 for [Fe(terpy)2]2+ (terpy = 2,2':6',2''-terpyridine). The data were analyzed in the context of semi-classical Marcus theory. Changes in the ratio of the electronic coupling to reorganization energy (specifically, H ab 4/λ) reveal an approximately two-fold difference between the [Fe(bpy')3]2+ complexes (∼1/30) and [Fe(terpy)2]2+ (∼1/14), suggesting a change in the nature of the nuclear coordinate associated with ground state recovery between these two types of complexes. These experimentally-determined ratios, along with estimates for the 5T2/1A1 energy gap, yield electronic coupling values between these two states for the [Fe(bpy')3]2+ series and [Fe(terpy)2]2+ of 4.3 ± 0.3 cm-1 and 6 ± 1 cm-1, respectively, values that are qualitatively consistent with the second-order nature of high-spin/low-spin coupling in a d6 ion. In addition to providing useful quantitative information on these prototypical Fe(ii) complexes, these results underscore the utility of variable-temperature spectroscopic measurements for characterizing ultrafast excited state dynamics in this class of compounds.

Defining the molecular signatures of human right heart failure.

AIMS: Right ventricular failure (RVF) varies significantly from the more common left ventricular failure (LVF). This study was undertaken to determine potential molecular pathways that are important in human right ventricular (RV) function and may mediate RVF. MATERIALS AND METHODS: We analyzed mRNA of human non-failing LV and RV samples and RVF samples from patients with pulmonary arterial hypertension (PAH), and post-LVAD implantation. We then performed transcript analysis to determine differential expression of genes in the human heart samples. Immunoblot quantification was performed followed by analysis of non-failing and failing phenotypes. KEY FINDINGS: Inflammatory pathways were more commonly dysregulated in RV tissue (both non-failing and failing phenotypes). In non-failing human RV tissue we found important differences in expression of FIGF, TRAPPAC, and CTGF suggesting that regulation of normal RV and LV function are not the same. In failing RV tissue, FBN2, CTGF, SMOC2, and TRAPP6AC were differentially expressed, and are potential targets for further study. SIGNIFICANCE: This work provides some of the first analyses of the molecular heterogeneity between human RV and LV tissue, as well as key differences in human disease (RVF secondary to pulmonary hypertension and LVAD mediated RVF). Our transcriptional data indicated that inflammatory pathways may be more important in RV tissue, and changes in FIGF and CTGF supported this hypothesis. In PAH RV failure samples, upregulation of FBN2 and CTGF further reinforced the potential significance that altered remodeling and inflammation play in normal RV function and failure.

Comparison of two- and three-times-daily topical ophthalmic application of 0.005% latanoprost solution in clinically normal dogs.

OBJECTIVE: To determine whether 2- or 3-times-daily application of topical ophthalmic 0.005% latanoprost solution is more effective at lowering intraocular pressure (IOP) in clinically normal dogs. ANIMALS: 9 clinically normal dogs. PROCEDURES: For each dog, I drop of latanoprost 0.005% solution was applied to 1 eye every 8 or 12 hours each day for 5 days; the contralateral eye received topical ophthalmic treatment with 1 drop of saline (0.9% NaCl) solution at the times of latanoprost application. Ocular examinations of both eyes were performed every 6 hours starting 48 hours prior to and ending 42 hours after the treatment period. Following a 5-week washout interval, the procedures were repeated but the previously latanoprost-treated eye of each dog received latanoprost application at the alternate frequency. RESULTS: Mean ± SD IOP reduction in the latanoprost-treated eyes was 31 ± 6.9% with 2-times-daily application and 33 ± 8.2% with 3-times-daily application. A 2-way repeated-measures ANOVA revealed significant differences in IOP with contributions by treatment (2 or 3 times daily), time of day (diurnal variation), and individual dog. The maximum mean daily IOP reduction in latanoprost-treated eyes was detected on day 3 of latanoprost treatment in each group. Eyes treated 3 times daily had significantly smaller pupil diameter and greater conjunctival hyperemia than eyes treated 2 times daily. CONCLUSIONS AND CLINICAL RELEVANCE: The clinical importance of the ocular hypotensive effects of 3-times-daily topical ophthalmic application of 0.005% latanoprost solution in dogs with glaucoma warrants investigation.