Associations between Parenting and Cognitive and Language Abilities at 2 Years of Age Depend on Prenatal Exposure to Disadvantage.

OBJECTIVE: To investigate whether parenting or neonatal brain volumes mediate associations between prenatal social disadvantage (PSD) and cognitive/language abilities and whether these mechanisms vary by level of disadvantage. STUDY DESIGN: Pregnant women were recruited prospectively from obstetric clinics in St Louis, Missouri. PSD encompassed access to social (eg, education) and material (eg, income to needs, health insurance, area deprivation, and nutrition) resources during pregnancy. Neonates underwent brain magnetic resonance imaging. Mother-child dyads (n = 202) returned at age 1 year for parenting observations and at age 2 years for cognition/language assessments (Bayley Scales of Infant and Toddler Development, Third Edition). Generalized additive and mediation models tested hypotheses. RESULTS: Greater PSD associated nonlinearly with poorer cognitive/language scores. Associations between parenting and cognition/language were moderated by disadvantage, such that supportive and nonsupportive parenting behaviors related only to cognition/language in children with lesser PSD. Parenting mediation effects differed by level of disadvantage: both supportive and nonsupportive parenting mediated PSD-cognition/language associations in children with lesser disadvantage, but not in children with greater disadvantage. PSD-associated reductions in neonatal subcortical grey matter (ß = 0.19; q = 0.03), white matter (ß = 0.23; q = 0.02), and total brain volume (ß = 0.18; q = 0.03) were associated with lower cognition, but did not mediate the associations between PSD and cognition. CONCLUSIONS: Parenting moderates and mediates associations between PSD and early cognition and language, but only in families with less social disadvantage. These findings, although correlational, suggest that there may be a critical threshold of disadvantage, below which mediating or moderating factors become less effective, highlighting the importance of reducing disadvantage as primary prevention.

Characterizing the vaginal microbiome in a sexually fluid primate (Pan paniscus).

While there have been recent breakthroughs in human vaginal microbiome research, very few non-human primate (NHP) vaginal microbiome studies exist due to difficulty in obtaining samples. In this study, we sought to: (1) characterize the bonobo vaginal microbiota for the first time, and (2) determine the relationship between vaginal pH and swelling size. During a 21-day study period, we collected observational data and 71 vaginal swabs from three cohoused adult females at the Ape Cognition and Conservation Initiative. After filtering and classification, a total of 3452 amplicon sequence variants were recruited from 12 vaginal samples. The most dominant phylum represented was Actinobacteria, and the most abundant genera were Gardnerella, Atopobium, and Prevotella. The mean pH score was 6.1 (range: 5.1-7.0), and pH levels varied with relative swelling size. This is the first study to examine the vaginal microbial composition in this species, and it conforms to previous NHP studies in that there was not the same bacterial dominance of Lactobacillus spp. often highlighted in human vaginal microbiota studies. Our findings suggest there may be other factors contributing to the protection of the bonobo vaginal environment, but future analysis of a larger sample is needed to fully understand how sociality and sexuality shape vaginal microbiota and host health.

Hand Infections in End-Stage Renal Disease-Consider Tumoral Calcinosis.

Tumoral calcinosis (TC) is a rare condition defined by the accumulation of calcium salts in soft tissues surrounding joints, most commonly large joints. Chronic joint inflammation in the setting of local hyperphosphatemia leads to interruption and dysfunction of tissue repair and generates breakdown products that subsequently calcify and accumulate. We present a case of a 42-year-old man with a history of end-stage renal disease on dialysis presenting to the clinic with a painless digital mass of his right long finger at the proximal interphalangeal joint. Our initial impression was a splinter abscess based on presentation and patient history. Although our patient's presentation of traumatic, painless TC of the hand secondary to end-stage renal disease is rare, the pathogenic mechanisms behind TC support this presentation. The authors recommend including TC within the differential of presentations similar to that of chronic abscess or giant cell tumor, especially when their medical history includes end-stage renal disease.

Using Separate Single-Outcome Risk Presentations Instead of Integrated Multioutcome Formats Improves Comprehension in Discrete Choice Experiments.

INTRODUCTION: Despite decades of research on risk-communication approaches, questions remain about the optimal methods for conveying risks for different outcomes across multiple time points, which can be necessary in applications such as discrete choice experiments (DCEs). We sought to compare the effects of 3 design factors: 1) separated versus integrated presentations of the risks for different outcomes, 2) use or omission of icon arrays, and 3) vertical versus horizontal orientation of the time dimension. METHODS: We conducted a randomized study among a demographically diverse sample of 2,242 US adults recruited from an online panel (mean age 59.8 y, s = 10.4 y; 21.9% African American) that compared risk-communication approaches that varied in the 3 factors noted above. The primary outcome was the number of correct responses to 12 multiple-choice questions asking survey respondents to identify specific numbers, contrast options to recognize dominance (larger v. smaller risks), and compute differences. We used linear regression to test the effects of the 3 design factors, controlling for health literacy, graph literacy, and numeracy. We also measured choice consistency in a subsequent DCE choice module. RESULTS: Mean comprehension varied significantly across versions (P < 0.001), with higher comprehension in the 3 versions that provided separated risk information for each risk. In the multivariable regression, separated risk presentation was associated with 0.58 more correct responses (P < 0.001; 95% confidence interval: 0.39, 0.77) compared with integrated risk information. Neither providing icon arrays nor using vertical versus horizontal time formats affected comprehension rates, although participant understanding did correlate with DCE choice consistency. CONCLUSIONS: In presentations of multiple risks over multiple time points, presenting risk information separately for each health outcome appears to increase understanding. HIGHLIGHTS: When conveying information about risks of different outcomes at multiple time points, separate presentations of single-outcome risks resulted in higher comprehension than presentations that combined risk information for different outcomes.We also observed benefits of presenting single-outcome risks separately among respondents with lower numeracy and graph literacy.Study participants who scored higher on risk understanding were more internally consistent in their responses to a discrete choice experiment.

Implementation of an Enhanced Recovery After Surgery Protocol for Cleft Palate Repair.

OBJECTIVE: This study examines an Enhanced Recovery After Surgery (ERAS) protocol for patients with cleft palate and hypothesizes that patients who followed the protocol would have decreased hospital length of stay and decreased narcotic usage than those who did not. DESIGN: Retrospective cohort study. SETTING: The study takes place at a single tertiary children's hospital. PATIENTS: All patients who underwent cleft palate repair during a 10-year period (n = 242). INTERVENTIONS: All patients underwent cleft palate repair with the most recent cohort following a new ERAS protocol. MAIN OUTCOME MEASURES: Primary outcomes included hospital length of stay and narcotic usage in the first 24 hours after surgery. RESULTS: Use of local bupivacaine during surgery was associated with decreased initial 24-hour morphine equivalent usage: 2.25 vs 3.38 mg morphine equivalent (MME) (P < 0.01), and a decreased hospital length of stay: 1.71 days vs 2.27 days (P < 0.01). The highest 24-hour morphine equivalent a patient consumed prior to the ERAS protocol implementation was 24.53 MME, compared with 6.3 MME after implementation. Utilization of the ERAS protocol was found to be associated with a decreased hospital length of stay: 1.67 vs 2.18 days (P < 0.01). CONCLUSIONS: Use of the proposed ERAS protocol may lead to lower narcotic usage and decreased length of stay.

Longitudinal Speech and Fistula Outcomes Following Primary Cleft Palate Repair at a Single Institution.

INTRODUCTION: Fistula formation and velopharyngeal insufficiency (VPI) are complications of cleft palate repair that often require surgical correction. The goal of the present study was to examine a single institution's experience with cleft palate repair with respect to fistula formation and need for surgery to correct velopharyngeal dysfunction. METHODS: Institutional review board approval was obtained. Patient demographics and operative details over a 10-year period were collected. Primary outcomes measured were development of fistula and need for surgery to correct VPI. Chi-square tests and independent t tests were utilized to determine significance (0.05). RESULTS: Following exclusion of patients without enough information for analysis, 242 patients were included in the study. Fistulas were reported in 21.5% of patients, and surgery to correct velopharyngeal dysfunction was needed in 10.7% of patients. Two-stage palate repair was associated with need for surgery to correct VPI (P = 0.014). Furlow palatoplasty was associated with decreased rate of fistula formation (P = 0.002) and decreased need for surgery to correct VPI (P = 0.014). CONCLUSION: This study reiterates much of the literature regarding differing cleft palate repair techniques. A 2-stage palate repair is often touted as having less growth restriction, but the present study suggests this may yield an increased need for surgery to correct VPI. Prior studies of Furlow palatoplasty have demonstrated an association with higher rates of fistula formation. The present study demonstrated a decreased rate of fistula formation with the Furlow technique, which may be due to the use of the Children's Hospital of Philadelphia modification. This study suggests clinically superior outcomes of the Furlow palatoplasty over other techniques.

Fe-S cluster biosynthesis and maturation: Mass spectrometry-based methods advancing the field.

Iron­sulfur (FeS) clusters are inorganic protein cofactors that perform essential functions in many physiological processes. Spectroscopic techniques have historically been used to elucidate details of FeS cluster type, their assembly and transfer, and changes in redox and ligand binding properties. Structural probes of protein topology, complex formation, and conformational dynamics are also necessary to fully understand these FeS protein systems. Recent developments in mass spectrometry (MS) instrumentation and methods provide new tools to investigate FeS cluster and structural properties. With the unique advantage of sampling all species in a mixture, MS-based methods can be utilized as a powerful complementary approach to probe native dynamic heterogeneity, interrogate protein folding and unfolding equilibria, and provide extensive insight into protein binding partners within an entire proteome. Here, we highlight key advances in FeS protein studies made possible by MS methodology and contribute an outlook for its role in the field.

Patients Requiring Multiple Surgeries for Velopharyngeal Insufficiency: Findings From a 10-Year Retrospective Review.

This study analyzed patients undergoing multiple surgeries for velopharyngeal insufficiency (VPI) and reviewed their preoperative evaluations and techniques selected for subsequent surgeries. A retrospective chart review was performed including patients having undergone multiple surgeries for VPI at the authors' institution between 2012 and 2022. All patients were evaluated and managed at the author's institution under the direction of 4 senior surgeons. The objective of this study was to provide insight into preoperative evaluation, surgical technique selection, and other factors that may contribute to patients who require multiple VPI surgeries. Of 71 patients having undergone surgery for VPI, 8 required at least 1 additional operation for persistent VPI following the initial intervention. Six patients who initially underwent a superiorly based posterior pharyngeal flap (PPF) required additional surgery, and for those patients' subsequent operations, 5 different techniques were used throughout their treatment. Of the remaining 2 patients who had multiple VPI surgeries, 1 initially received autologous fat transfer and 1 initially underwent a furlow palatoplasty. Finally, 0 patients that initially underwent buccal flaps or collagen injection required further unplanned surgical intervention. This study demonstrates the importance of selecting an appropriate surgical approach when operating on patients following a failed VPI surgery. The algorithm developed from these findings emphasizes the importance of properly identifying the anatomical deficiency resulting from the failed intervention. A review of the advantages of nasopharyngoscopy as a preoperative evaluative technique of velopharyngeal form and function when compared to lateral barium video fluoroscopy was also included.

Mandibular Distraction in Patients With Pierre Robin Sequence: A Multisurgeon Experience.

OBJECTIVE: Mandibular distraction osteogenesis (MDO) is rapidly becoming a standard of care for management of patients with severe Pierre Robin sequence. The tongue is brought forward to alleviate airway obstruction. This study will look at an institutional, multisurgeon experience with MDO over 10 years. DESIGN: A retrospective chart review was conducted. SETTING: All patients who underwent MDO at the authors' institution from 2012 to 2022 were included. Three craniofacial surgeons performed all interventions. PATIENTS: Demographics, preoperative and postoperative respiratory and feeding status, and distraction data were collected for 27 patients meeting inclusion criteria. MAIN OUTCOME MEASURES: Primary outcomes were avoidance of a gastrostomy tube, avoidance of a tracheostomy, discharge from hospital on room air, and complications. A significance value of 0.05 was utilized. RESULTS: The average age at MDO was 135 days, mean activation phase was 13.6 days, mean distraction length was 14.9 mm, and mean consolidation phase was 64.2 days. A longer activation phase was associated with discharge with a gastrostomy tube and a shorter activation phase was associated with discharge on full oral feeds. The ability to discharge on room air was associated with a shorter latency phase, shorter activation phase, and decreased distance of distraction. CONCLUSIONS: The goal of MDO is to achieve full oral feeds with no respiratory support. Several different latency periods were used in this study, and a short latency period was demonstrated to be safe.

Determining the plant-pollinator network in a culturally significant food and medicine garden in the Great Lakes region.

Understanding the interactions between plants and pollinators within a system can provide information about pollination requirements and the degree to which species contribute to floral reproductive success. Past research has focused largely on interactions within monocultured agricultural systems and only somewhat on wild pollination networks. This study focuses on the culturally significant Three Sisters Garden, which has been grown and tended by many Indigenous peoples for generations in the Great Lakes Region. Here, the plant-pollinator network of the traditional Three Sisters Garden with the inclusion of some additional culturally significant plants was mapped. Important visitors in this system included the common eastern bumble bee, Bombus impatiens Cresson (Hymenoptera: Apidae), and the hoary squash bee, Xenoglossa pruinosa (Say) (Hymenoptera: Apidae), as determined by their abundances and pollinator service index (PSI) values. Understanding the key pollinators in the Three Sisters Garden links biological diversity to cultural diversity through the pollination of culturally significant plants. Further, this information could be of use in supporting Indigenous food sovereignty by providing knowledge about which wild pollinators could be supported to increase fruit and seed set within the Three Sisters Garden. Our findings can also lead to more effective conservation of important wild pollinator species.

Characteristics of women concordant and discordant for urine drug screens for cannabis exposure and self-reported cannabis use during pregnancy.

BACKGROUND: Increasing cannabis use among pregnant people and equivocal evidence linking prenatal cannabis exposure to adverse outcomes in offspring highlights the need to understand its potential impact on pregnancy and child outcomes. Assessing cannabis use during pregnancy remains a major challenge with potential influences of stigma on self-report as well as detection limitations of easily collected biological matrices. OBJECTIVE: This descriptive study examined the concordance between self-reported (SR) cannabis use and urine drug screen (UDS) detection of cannabis exposure during the first trimester of pregnancy and characterized concordant and discordant groups for sociodemographic factors, modes of use, secondhand exposure to cannabis and tobacco, and alcohol use and cotinine positivity. STUDY DESIGN: The Cannabis Use During Development and Early Life (CUDDEL) Study is an ongoing longitudinal study that recruits pregnant individuals presenting for obstetric care, who report lifetime cannabis use as well as using (n = 289) or not using cannabis (n = 169) during pregnancy. During the first trimester pregnancy visit, SR of cannabis use and a UDS for cannabis, other illicit drugs and nicotine are acquired from eligible participants, of whom 333 as of 05/01/2023 had both. RESULTS: Using available CUDDEL Study data on both SR and UDS (n = 333; age 26.6 ± 4.7; 88.6% Black; 45.4% below federal poverty threshold; 56.5% with paid employment; 89% with high school education; 22% first pregnancy; 12.3 ± 3.6 weeks gestation), we classified pregnant individuals with SR and UDS data into 4 groups based on concordance (k = 0.49 [95% C.I. 0.40-0.58]) between SR cannabis use and UDS cannabis detection during the first trimester: 1) SR+/UDS+ (n = 107); 2) SR-/UDS- (n = 142); 3) SR+/UDS- (n = 44); 4) SR-/UDS+ (n = 40). Those who were SR+/UDS- reported less frequent cannabis use and fewer hours under the influence of cannabis during their pregnancy. Those who were SR-/UDS+ were more likely to have joined the study at a lower gestational age with 62.5% reporting cannabis use during their pregnancy prior to being aware that they were pregnant. Of the 40 SR-/UDS+ women, 14 (i.e., 35%) reported past month secondhand exposure, or blunt usage. In the subset of individuals with SR and UDS available at trimester 2 (N = 160) and 3 (N = 140), concordant groups were mostly stable and > 50% of those in the discordant groups became concordant by the second trimester. Classifying individuals as exposed or not exposed who were SR+ and/or UDS+ resulted in minor changes in group status based on self-report at screening. CONCLUSION: Overall, there was moderate concordance between SR and UDS for cannabis use/exposure during pregnancy. Instances of SR+/UDS- discordancy may partially be attributable to lower levels of use that are not detected on UDS. SR-/UDS+ discordancy may arise from recent use prior to knowledge of pregnancy, extreme secondhand exposure, deception, and challenges with completing questionnaires. Acquiring both self-report and biological detection of cannabis use/exposure allows for the examination of convergent evidence. Classifying those who are SR+ and/or UDS+ as individuals who used cannabis during their first trimester after being aware of their pregnancy resulted in only a minor change in exposure status; thus, relying on self-report screening, at least in this population and within this sociocultural context likely provides an adequate approximation of cannabis use during pregnancy.

Patient Risk-Benefit Preferences for Transcatheter Versus Surgical Mitral Valve Repair.

BACKGROUND: Transcatheter edge-to-edge repair (TEER) of mitral regurgitation is less invasive than surgery but has greater 5-year mortality and reintervention risks, and leads to smaller improvements in physical functioning. The study objective was to quantify patient preferences for risk-benefit trade-offs associated with TEER and surgery. METHODS AND RESULTS: A discrete choice experiment survey was administered to patients with mitral regurgitation. Attributes included procedure type; 30-day mortality risk; 5-year mortality risk and physical functioning for 5 years; number of hospitalizations in the next 5 years; and risk of additional surgery in the next 5 years. A mixed-logit regression model was fit to estimate preference weights. Two hundred one individuals completed the survey: 63% were female and mean age was 74 years. On average, respondents preferred TEER over surgery. To undergo a less invasive procedure (ie, TEER), respondents would accept up to a 13.3% (95% CI, 8.7%-18.5%) increase in reintervention risk above a baseline of 10%, 4.6 (95% CI, 3.1-6.2) more hospitalizations above a baseline of 1, a 10.7% (95% CI, 6.5%-14.5%) increase in 5-year mortality risk above a baseline of 20%, or more limited physical functioning representing nearly 1 New York Heart Association class (0.7 [95% CI, 0.4-1.1]) over 5 years. CONCLUSIONS: Patients in general preferred TEER over surgery. When holding constant all other factors, a functional improvement from New York Heart Association class III to class I maintained over 5 years would be needed, on average, for patients to prefer surgery over TEER.

IL-27 alters inflammatory cytokine expression and limits protective immunity against Mycobacterium tuberculosis in a neonatal BCG vaccination model.

Background: Efforts to control tuberculosis (TB), caused by the pathogen Mycobacterium tuberculosis (Mtb), have been hampered by the immense variability in protection from BCG vaccination. While BCG protects young children from some forms of TB disease, long-term protection against pulmonary disease is more limited, suggesting a poor memory response. New vaccines or vaccination strategies are required to have a realistic chance of eliminating TB disease. In TB endemic areas, routine immunization occurs during the neonatal period and as such, we hypothesized that inadequate protective immunity elicited by BCG vaccination could be the result of the unique early-life immune landscape. Interleukin (IL)-27 is a heterodimeric cytokine with immune suppressive activity that is elevated in the neonatal period. Objective: We investigated the impact of IL-27 on regulation of immune responses during neonatal BCG vaccination and protection against Mtb. Methods: Here, we used a novel model of neonatal vaccination and adult aerosol challenge that models the human timeline of vaccine delivery and disease transmission. Results: Overall, we observed improved control of Mtb in mice unresponsive to IL-27 (IL-27Rα-/-) that was consistent with altered expression patterns of IFN-γ and IL-17 in the lungs. The balance of these cytokines with TNF-α expression may be key to effective bacterial clearance. Conclusions: Our findings suggest the importance of evaluating new vaccines and approaches to combat TB in the neonatal population most likely to receive them as part of global vaccination campaigns. They further indicate that temporal strategies to antagonize IL-27 during early life vaccination may improve protection.

Stated-Preference Survey Design and Testing in Health Applications.

Following the conceptualization of a well-formulated and relevant research question, selection of an appropriate stated-preference method, and related methodological issues, researchers are tasked with developing a survey instrument. A major goal of designing a stated-preference survey for health applications is to elicit high-quality data that reflect thoughtful responses from well-informed respondents. Achieving this goal requires researchers to design engaging surveys that maximize response rates, minimize hypothetical bias, and collect all the necessary information needed to answer the research question. Designing such a survey requires researchers to make numerous interrelated decisions that build upon the decision context, selection of attributes, and experimental design. Such decisions include considering the setting(s) and study population in which the survey will be administered, the format and mode of administration, and types of contextual information to collect. Development of a survey is an interactive process in which feedback from respondents should be collected and documented through qualitative pre-test interviews and pilot testing. This paper describes important issues to consider across all major steps required to design and test a stated-choice survey to elicit patient preferences for health preference research.

Development and testing of patient-centered education about hormone replacement therapy for women at high genetic risk of breast and ovarian cancer.

OBJECTIVE: In this study, we aimed to develop education to assist BRCA mutation carriers in making informed decisions about HRT in the context of risk-reducing surgery, while simultaneously clarifying their treatment-specific values and reducing decisional conflict. METHODS: We enrolled premenopausal BRCA mutation carriers ages 19-49 without prior cancer or risk-reducing salpingo-oophorectomy to structured interviews in which they reviewed education about the risks and benefits of HRT. Materials included literature-derived data demonstrating associations between HRT and commonly considered health outcomes (breast cancer, vasomotor symptoms, sexual functioning, cardiovascular disease, osteoporosis, and blood clots). Participants completed the 16-item Decisional Conflict Scale (DCS) before and after education, communicated their preferences by rating and ranking the six outcomes, and provided feedback to inform iterative revisions of the educational content. RESULTS: 25 participants completed interviews. DCS scores decreased significantly from 54.6 to 22.8 following education (p < 0.001); sub-scores for uncertainty (71.7 to 37.3), informed (71.7 to 15.3), values clarity (53.7 to 17.0), effective decision (44.2 to 25.5), and support (35.0 to 17.7) also decreased significantly. Participants ranked cardiovascular disease as the most important outcome to consider, followed by breast cancer, osteoporosis, blood clots, decline in sexual function, and hot flashes. Participants with prior mastectomy (N = 10) ranked breast cancer as the most important outcome 25% of the time, compared to 80% in participants without mastectomy (N = 15). CONCLUSION: Following education, BRCA mutation carriers had significantly less decisional conflict regarding the choice to use HRT. This pilot study was successful in generating a prototype educational aid for further testing.

Neighborhood Crime and Externalizing Behavior in Toddlers: A Longitudinal Study With Neonatal fMRI and Parenting.

OBJECTIVE: Prenatal exposure to neighborhood crime has been associated with weaker neonatal frontolimbic connectivity; however, associations with early childhood behavior remain unclear. We hypothesized that living in a high-crime neighborhood would be related to higher externalizing symptoms at age 1 and 2 years, over and above other adversities, and that neonatal frontolimbic connectivity and observed parenting behaviors at 1 year would mediate this relationship. METHOD: Participants included 399 pregnant women, recruited as part of the Early Life Adversity, Biological Embedding, and Risk for Developmental Precursors of Mental Disorders (eLABE) study. Geocoded neighborhood crime data was obtained from Applied Geographic Solution. A total of 319 healthy, non-sedated neonates underwent scanning using resting-state functional magnetic resonance imaging (fMRI) on a Prisma 3T scanner and had ≥10 minutes of high-quality data. Infant-Toddler Socioemotional Assessment Externalizing T scores were available for 274 mothers of 1-year-olds and 257 mothers of 2-year-olds. Observed parenting behaviors were available for 202 parent-infant dyads at 1 year. Multilevel and mediation models tested longitudinal associations. RESULTS: Living in a neighborhood with high violent (ß = 0.15, CI = 0.05-0.27, p = .004) and property (ß = 0.10, CI = 0.01-0.20, p = .039) crime was related to more externalizing symptoms at 1 and 2 years, controlling for other adversities. Weaker frontolimbic connectivity was also associated with higher externalizing symptoms at 1 and 2 years. After controlling for other adversities, parenting behaviors mediated the specific association between crime and externalizing symptoms, but frontolimbic connectivity did not. CONCLUSION: These findings provide evidence that early exposure to neighborhood crime and weaker neonatal frontolimbic connectivity may influence later externalizing symptoms, and suggest that parenting may be an early intervention target for families in high-crime areas. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Investigating Substituent Interactions with Cationic Catalysts.

Rates of isothiourea catalyzed silylation and acylation reactions were measured for substrates with various electronic substituents at the aryl group. Through these measurements, the intermolecular interactions between cationic catalyst intermediates and different aryl groups were explored. These studies were performed to understand how changes in the catalyst structure affected electrostatic intermolecular interactions. Three different catalysts (N-methylimidazole and two isothioureas) were employed that varied in their ability to delocalize their cationic nature. The results show that more delocalization on the catalyst reduces the sensitivity to the electronics on the aryl group. Surprisingly, the isothiourea with a fused benzene ring provided additional points of interaction with groups that contained lone-pairs, significantly affecting the overall rate. This work helps explore the interactions that dominate in these types of catalytic systems, to aid in future organocatalysis development. Density functional theory (DFT) studies further confirmed isothiourea/aryl ring interaction with the alcohol substrate in the acylation process, which confirmed these hypotheses. Electron rich or lone-pair bearing functional groups stabilize the cationic catalyst core, thereby stabilizing the transition states and accelerating the reaction. It was also discovered that in one case, the formation of a stable substrate dimer was responsible for its lower reactivity.

Relationship of Race With Functional and Clinical Outcomes With the REHAB-HF Multidomain Physical Rehabilitation Intervention for Older Patients With Acute Heart Failure.

Background The REHAB-HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) randomized trial demonstrated that a 3-month transitional, tailored, progressive, multidomain physical rehabilitation intervention improves physical function, frailty, depression, and health-related quality of life among older adults with acute decompensated heart failure. Whether there is differential intervention efficacy by race is unknown. Methods and Results In this prespecified analysis, differential intervention effects by race were explored at 3 months for physical function (Short Physical Performance Battery [primary outcome], 6-Minute Walk Distance), cognition, depression, frailty, health-related quality of life (Kansas City Cardiomyopathy Questionnaire, EuroQoL 5-Dimension-5-Level Questionnaire) and at 6 months for hospitalizations and death. Significance level for interactions was P≤0.1. Participants (N=337, 97% of trial population) self-identified in near equal proportions as either Black (48%) or White (52%). The Short Physical Performance Battery intervention effect size was large, with values of 1.3 (95% CI, 0.4-2.1; P=0.003]) and 1.6 (95% CI, 0.8-2.4; P<0.001) in Black and White participants, respectively, and without significant interaction by race (P=0.56). Beneficial effects were also demonstrated in 6-Minute Walk Distance, gait speed, and health-related quality of life scores without significant interactions by race. There was an association between intervention and reduced all-cause rehospitalizations in White participants (rate ratio, 0.73 [95% CI, 0.55-0.98]; P=0.034) that appears attenuated in Black participants (rate ratio, 1.06 [95% CI, 0.81-1.41]; P=0.66; interaction P=0.067). Conclusions The intervention produced similarly large improvements in physical function and health-related quality of life in both older Black and White patients with acute decompensated heart failure. A future study powered to determine how the intervention impacts clinical events is required. REGISTRATION URL: https://www.clinicaltrials.gov. Identifier: NCT02196038.