Perceptions of HIV self-testing promotion in black barbershop businesses: implications for equitable engagement of black-owned small businesses for public health programs.

BACKGROUND: HIV self-testing (HIVST) offers an innovative and promising approach to increasing HIV testing among Black men in the United States, a population disproportionately affected by HIV. However, engaging Black men in traditional HIV prevention programs has been challenging due to stigma, medical mistrust, and limited access to preventive health services. This formative qualitative study aimed to explore the potential of utilizing barbershops as an example of a nontraditional healthcare venue to promote and distribute HIVST. METHODS: Four virtual focus group discussions (FGDs) consisting of 19 participants in North Carolina were conducted with Black men, including barbershop business owners, barbers, and their customers, to assess perceptions of HIVST and the acceptability of partnering with barbershop businesses to promote HIVST. FGDs were digitally recorded, transcribed, and analyzed using a deductive coding approach to thematic analysis. RESULTS: Participants reported that the trusting relationship between barbers and their customers, which may not exist between Black men and health care providers, is a facilitator of collaborating with barbershop businesses to reach Black men for HIVST distribution. Participants recommended providing education for barbers on the use of HIVST, as well as how to inform self-testers about linkage to care following HIVST to build the credibility of the barbers in delivering the intervention. Participants also raised the issue of the cost of HIVST to barbershop customers as a potential barrier to implementation, as well as the possibility that the implementation of such interventions could be seen as out of place in a barbershop business venue. Participants also expressed a strong belief that compensation to barbershops and their employees should accompany any intervention. CONCLUSION: These findings suggest that barbershop business venues may provide an appropriate venue for HIVST promotion and distribution, though factors like cost, training, and incentivization of implementers are necessary to consider in implementation planning. Furthermore, partnerships between public health actors and the business community must be built on equitable engagement to ensure the long-term viability of these critical initiatives.

Tracking Li atoms in real-time with ultra-fast NMR simulations.

We present for the first time a multiscale machine learning approach to jointly simulate atomic structure and dynamics with the corresponding solid state Nuclear Magnetic Resonance (ssNMR) observables. We study the use-case of spin-alignment echo (SAE) NMR for exploring Li-ion diffusion within the solid state electrolyte material Li3PS4 (LPS) by calculating quadrupolar frequencies of 7Li. SAE NMR probes long-range dynamics down to microsecond-timescale hopping processes. Therefore only a few machine learning force field schemes are able to capture the time- and length scales required for accurate comparison with experimental results. By using a new class of machine learning interatomic potentials, known as ultra-fast potentials (UFPs), we are able to efficiently access timescales beyond the microsecond regime. In tandem, we have developed a machine learning model for predicting the full 7Li electric field gradient (EFG) tensors in LPS. By combining the long timescale trajectories from the UFP with our model for 7Li EFG tensors, we are able to extract the autocorrelation function (ACF) for 7Li quadrupolar frequencies during Li diffusion. We extract the decay constants from the ACF for both crystalline ß-LPS and amorphous LPS, and find that the predicted Li hopping rates are on the same order of magnitude as those predicted from the Li dynamics. This demonstrates the potential for machine learning to finally make predictions on experimentally relevant timescales and temperatures, and opens a new avenue of NMR crystallography: using machine learning dynamical NMR simulations for accessing polycrystalline and glass ceramic materials.

The EFG Rosetta Stone: translating between DFT calculations and solid state NMR experiments.

We present a comprehensive study on the best practices for integrating first principles simulations in experimental quadrupolar solid-state nuclear magnetic resonance (SS-NMR), exploiting the synergies between theory and experiment for achieving the optimal interpretation of both. Most high performance materials (HPMs), such as battery electrodes, exhibit complex SS-NMR spectra due to dynamic effects or amorphous phases. NMR crystallography for such challenging materials requires reliable, accurate, efficient computational methods for calculating NMR observables from first principles for the transfer between theoretical material structure models and the interpretation of their experimental SS-NMR spectra. NMR-active nuclei within HPMs are routinely probed by their chemical shielding anisotropy (CSA). However, several nuclear isotopes of interest, e.g.7Li and 27Al, have a nuclear quadrupole and experience additional interactions with the surrounding electric field gradient (EFG). The quadrupolar interaction is a valuable source of information about atomistic structure, and in particular, local symmetry, complementing the CSA. As such, there is a range of different methods and codes to choose from for calculating EFGs, from all-electron to plane wave methods. We benchmark the accuracy of different simulation strategies for computing the EFG tensor of quadrupolar nuclei with plane wave density functional theory (DFT) and study the impact of the material structure as well as the details of the simulation strategy. Especially for small nuclei with few electrons, such as 7Li, we show that the choice of physical approximations and simulation parameters has a large effect on the transferability of the simulation results. To the best of our knowledge, we present the first comprehensive reference scale and literature survey for 7Li quadrupolar couplings. The results allow us to establish practical guidelines for developing the best simulation strategy for correlating DFT to experimental data extracting the maximum benefit and information from both, thereby advancing further research into HPMs.

Inferring disease course from differential exon usage in the wide titinopathy spectrum.

OBJECTIVE: Biallelic titin truncating variants (TTNtv) have been associated with a wide phenotypic spectrum, ranging from complex prenatal muscle diseases with dysmorphic features to adult-onset limb-girdle muscular dystrophy, with or without cardiac involvement. Given the size and complexity of TTN, reaching an unequivocal molecular diagnosis and precise disease prognosis remains challenging. METHODS: In this case series, 12 unpublished cases and one already published case with biallelic TTNtv were collected from multiple international medical centers between November 2022 and September 2023. TTN mutations were detected through exome or genome sequencing. Information about familial and personal clinical history was collected in a standardized form. RNA-sequencing and analysis of TTN exon usage were performed on an internal sample cohort including postnatal skeletal muscles, fetal skeletal muscles, postnatal heart muscles, and fetal heart muscles. In addition, publicly available RNA-sequencing data was retrieved from ENCODE. RESULTS: We generated new RNA-seq data on TTN exons and identified genotype-phenotype correlations with prognostic implications for each titinopathy patient (whether worsening or improving in prenatal and postnatal life) using percentage spliced in (PSI) data for the involved exons. Interestingly, thanks to exon usage, we were also able to rule out a titinopathy diagnosis in one prenatal case. INTERPRETATION: This study demonstrates that exon usage provides valuable insights for a more exhaustive clinical interpretation of TTNtv; additionally, it may serve as a model for implementing personalized medicine in many other genetic diseases, since most genes undergo alternative splicing.

Autobiographical memory phenomenology in transgender and cisgender individuals.

Transgender individuals face challenges to identity as they transition from their sex assigned at birth to their affirmed gender. Memories may support a sense of self through the recall of events with more phenomenological detail than others, making them feel closer to the current self. Autobiographical memories of 90 transgender and 90 cisgender adults were compared on self-reported memory phenomenology. Memory phenomenology was more variable in transgender individuals, with a larger difference between phenomenological ratings of recent and distant memories. Memory phenomenology specifically varied in relation to the timing of coming out to a parent. High points reported after this time were rated with higher phenomenological quality and these ratings were linked to positive well-being. Results affirm the relevance of phenomenological continuity to the identity of transgender individuals, suggesting that events from before coming out are recalled with less phenomenological quality than events after coming out.

Deployment of attractive targeted sugar baits in western Zambia: installation, monitoring, removal, and disposal procedures during a Phase III cluster randomized controlled trial.

BACKGROUND: Attractive Targeted Sugar Baits (ATSBs) offer a complementary vector control strategy to interventions targeting blood feeding or larval control by attacking the sugar feeding behaviour of adult mosquitoes using an attract-and-kill approach. Western Zambia was the first location to receive and deploy ATSB Sarabi version 1.2 stations in a Phase III cluster randomized controlled trial. This paper describes ATSB station installation, monitoring, removal, and disposal, quantifies ATSB station coverage, and reports major reasons for ATSB station replacement. METHODS: ATSB stations were deployed during two annual transmission seasons, through scheduled installation and removal campaigns. During deployment, monitoring was conducted per protocol to maintain high coverage of the ATSB stations in good condition. Routine monitoring visits during the trial captured details on ATSB station damage necessitating replacement following pre-defined replacement criteria. Annual cross-sectional household surveys measured ATSB station coverage during peak malaria transmission. RESULTS: A total of 67,945 ATSB stations were installed in Year 1 (41,695 initially installed+ 26,250 installed during monitoring) and 69,494 ATSB stations were installed in Year 2 (41,982 initially installed+ 27,512 installed during monitoring) across 35 intervention clusters to maintain high coverage of two ATSB stations in good condition per eligible household structure. The primary reasons for ATSB station replacement due to damage were holes/tears and presence of mold. Cross-sectional household surveys documented high coverage of ATSB stations across Year 1 and Year 2 with 93.1% of eligible structures having ≥ 2 ATSB stations in any condition. DISCUSSION: ATSB station deployment and monitoring efforts were conducted in the context of a controlled cRCT to assess potential product efficacy. Damage to ATSB stations during deployment required replacement of a subset of stations. High coverage of eligible structures was maintained over the two-year study despite replacement requirements. Additional research is needed to better understand the impact of damage on ATSB station effectiveness under programmatic conditions, including thresholds of threats to physical integrity and biological deterioration on product efficacy. CONCLUSIONS: Optimizing ATSB stations to address causes of damage and conducting implementation research to inform optimal delivery and cost-effective deployment will be important to facilitate scale-up of ATSB interventions.

Entomological effects of attractive targeted sugar bait station deployment in Western Zambia: vector surveillance findings from a two-arm cluster randomized phase III trial.

BACKGROUND: Attractive targeted sugar bait (ATSB) stations are a novel tool with potential to complement current approaches to malaria vector control. To assess the public health value of ATSB station deployment in areas of high coverage with standard vector control, a two-arm cluster-randomized controlled trial (cRCT) of Sarabi ATSB® stations (Westham Ltd., Hod-Hasharon, Israel) was conducted in Western Province, Zambia, a high-burden location were Anopheles funestus is the dominant vector. The trial included 70 clusters and was designed to measure the effect of ATSBs on case incidence and infection prevalence over two 7-month deployments. Reported here are results of the vector surveillance component of the study, conducted in a subset of 20 clusters and designed to provide entomological context to guide overall interpretation of trial findings. METHODS: Each month, 200 paired indoor-outdoor human landing catch (HLC) and 200 paired light trap (LT) collections were conducted to monitor An. funestus parity, abundance, biting rates, sporozoite prevalence, and entomological inoculation rates (EIR). RESULTS: During the study 20,337 female An. funestus were collected, 11,229 from control and 9,108 from intervention clusters. A subset of 3,131 HLC specimens were assessed for parity: The mean non-parous proportion was 23.0% (95% CI 18.2-28.7%, total n = 1477) in the control and 21.2% (95% CI 18.8-23.9%, total n = 1654) in the intervention arm, an OR = 1.05 (95% CI 0.82-1.34; p = 0.688). A non-significant reduction in LT abundance (RR = 0.65 [95% CI 0.30-1.40, p = 0.267]) was associated with ATSB deployment. HLC rates were highly variable, but model results indicate a similar non-significant trend with a RR = 0.68 (95%CI 0.22-2.00; p = 0.479). There were no effects on sporozoite prevalence or EIR. CONCLUSIONS: Anopheles funestus parity did not differ across study arms, but ATSB deployment was associated with a non-significant 35% reduction in vector LT density, results that are consistent with the epidemiological impact reported elsewhere. Additional research is needed to better understand how to maximize the potential impact of ATSB approaches in Zambia and other contexts. TRIAL REGISTRATION NUMBER: This trial was registered with Clinicaltrials.gov (NCT04800055, 16 March 2021).

Mothers' reflections on the diagnosis and birth of their child with Down syndrome: Variability based on the timing of the diagnosis.

Previous research has examined parents' reflections on their child's Down syndrome diagnosis based on whether the diagnosis was provided prenatally or after birth, revealing few significant differences; by comparison, few studies have examined parents' reflections on the birth of the child in relation to the timing of the diagnosis. This study was conducted to examine whether mothers differentially reported on and rated the diagnosis, birth, and most recent birthday of their child with DS based on when the diagnosis was provided. Forty-four American mothers of children with DS discussed the birth of their child, when they learned of their child's DS diagnosis, and their child's most recent birthday with a researcher. Participants also completed online questionnaires on which they rated the events and indicated how they felt about the events at the time of their occurrence and at the time of the study. The results revealed that participants who received a prenatal diagnosis of DS for their child reflected differently-and seemingly more positively-on their child's birth relative to participants who received a postnatal diagnosis. These differences were evident when considering participant ratings, emotion language used when discussing the events, and feeling states characterizing how participants felt about the events at the time of their occurrence and at the time of the study. Given these group differences, medical professionals should carefully consider the conditions under which they provide mothers with diagnostic information and support services after a child is born.

A Novel Method for In Situ RT-PCR Based on Capsules from Centrifuge Tubes, Ideal for Transcripts Detection in Plant Tissues.

In situ RT-PCR presents advantages over other expression analysis methods due to its rapid processing and low-cost equipment. However, this technique is not without its challenges. A protocol based on a capsule made from centrifuge tubes that offers advantages over slides is presented. This capsule protects histological sections from drying out, and its easy assembly reduces time pauses between incubations. In addition, the container size where the sample is deposited allows the addition and withdrawal of the different solutions. The capsule does not need previous sealing after each incubation, and, above all, it is a low-cost and accessible material. A guideline for tissue sectioning using a cryostat that offers advantages over other sectioning methods is also described.

Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice.

Activity-induced muscle pain increases interleukin-1ß (IL-1ß) release from muscle macrophages and the development of hyperalgesia is prevented by blockade of IL-1ß in muscle. Brain derived neurotrophic factor (BDNF) is released from sensory neurons in response to IL-1ß and mediates both inflammatory and neuropathic pain. Thus, we hypothesize that in activity-induced pain, fatigue metabolites combined with IL-1ß activate sensory neurons to increase BDNF release, peripherally in muscle and centrally in the spinal dorsal horn, to produce hyperalgesia. We tested the effect of intrathecal or intramuscular injection of BDNF-Tropomyosin receptor kinase B (TrkB) inhibitors, ANA-12 or TrkB-Fc, on development of activity-induced pain. Both inhibitors prevented the hyperalgesia when given before or 24hr after induction of the model in male but not female mice. BDNF messenger ribonucleic acid (mRNA) and protein were significantly increased in dorsal root ganglion (DRG) 24hr after induction of the model in both male and female mice. Blockade of IL-1ß in muscle had no effect on the increased BNDF mRNA observed in the activity-induced pain model, while IL-1ß applied to cultured DRG significantly induced BDNF expression, suggesting IL-1ß is sufficient but not necessary to induce BNDF. Thus, fatigue metabolites, combined with IL-1ß, upregulate BDNF in primary DRG neurons in both male and female mice, but contribute to activity-induced pain only in males.

Improving Quality and Cost of the Oncology Advanced Practice Provider Chemotherapy Privileging Process.

BACKGROUND: Managing antineoplastic orders, side effects, and symptoms is a primary role of oncology advanced practice providers (APPs). Antineoplastic management (ANM) is complex because of risk of medication errors, narrow therapeutic range of agents, frequent dose adjustments, and multiple drug regimens. OBJECTIVES: This article describes an academic institution's review of current practice for ANM privileging and employing Plan-Do-Study-Act (PDSA) cycles to develop a revised process relevant to APP practice, addressing efficiency, accessibility, and cost-effectiveness. METHODS: Using consecutive PDSA cycles, the team revised the didactic portion of the ANM privileging process and collaborated with nurses, pharmacists, and physicians for mentoring expertise. FINDINGS: The revised process resulted in increased relevance of ANM didactic content while requiring 75% less time to complete. To date, all ANM-privileged APPs at the institution (N = 49) have completed the revised ANM privileging process, with a 100% pass rate on the competency assessment.

Residual bioefficacy of attractive targeted sugar bait stations targeting malaria vectors during seasonal deployment in Western Province of Zambia.

BACKGROUND: The primary vector control interventions in Zambia are long-lasting insecticidal nets and indoor residual spraying. Challenges with these interventions include insecticide resistance and the outdoor biting and resting behaviours of many Anopheles mosquitoes. Therefore, new vector control tools targeting additional mosquito behaviours are needed to interrupt transmission. Attractive targeted sugar bait (ATSB) stations, which exploit the sugar feeding behaviours of mosquitoes, may help in this role. This study evaluated the residual laboratory bioefficacy of Westham prototype ATSB® Sarabi v.1.2.1 Bait Station (Westham Ltd., Hod-Hasharon, Israel) in killing malaria vectors in Western Province, Zambia, during the first year of a large cluster randomized phase-III trial (Clinical Trials.gov Identifier: NCT04800055). METHODS: This was a repeat cross-sectional study conducted within three districts, Nkeyema, Kaoma, and Luampa, in Western Province, Zambia. The study was conducted in 12 intervention clusters among the 70 trial clusters (35 interventions, 35 controls) between December 2021 and June 2022. Twelve undamaged bait stations installed on the outer walls of households were collected monthly (one per cluster per month) for bioassays utilizing adult female and male Anopheles gambiae sensu stricto (Kisumu strain) mosquitoes from a laboratory colony. RESULTS: A total of 84 field-deployed ATSB stations were collected, and 71 ultimately met the study inclusion criteria for remaining in good condition. Field-deployed stations that remained in good condition (intact, non-depleted of bait, and free of dirt as well as mold) retained high levels of bioefficacy (mean induced mortality of 95.3% in males, 71.3% in females, 83.9% combined total) over seven months in the field but did induce lower mortality rates than non-deployed ATSB stations (mean induced mortality of 96.4% in males, 87.0% in females, 91.4% combined total). There was relatively little variation in corrected mortality rates between monthly rounds for those ATSB stations that had been deployed to the field. CONCLUSION: While field-deployed ATSB stations induced lower mortality rates than non-deployed ATSB stations, these stations nonetheless retained relatively high and stable levels of bioefficacy across the 7-month malaria transmission season. While overall mean mosquito mortality rates exceeded 80%, mean mortality rates for females were 24 percentage points lower than among males and these differences merit attention and further evaluation in future studies. The duration of deployment was not associated with lower bioefficacy. Westham prototype ATSB stations can still retain bioefficacy even after deployment in the field for 7 months, provided they do not meet predetermined criteria for replacement.

Multi-Method Formative Evaluation of a Digital Online Grocery Shopping Assistant Among Special Supplemental Nutrition Program for Women, Infants, and Children Participants.

OBJECTIVE: Assess the acceptability of a digital grocery shopping assistant among rural women with low income. DESIGN: Simulated shopping experience, semistructured interviews, and a choice experiment. SETTING: Rural central North Carolina Special Supplemental Nutrition Program for Women, Infants, and Children clinic. PARTICIPANTS: Thirty adults (aged ≥18 years) recruited from a Special Supplemental Nutrition Program for Women, Infants, and Children clinic. PHENOMENON OF INTEREST: A simulated grocery shopping experience with the Retail Online Shopping Assistant (ROSA) and mixed-methods feedback on the experience. ANALYSIS: Deductive and inductive qualitative content analysis to independently code and identify themes and patterns among interview responses and quantitative analysis of simulated shopping experience and choice experiment. RESULTS: Most participants liked ROSA (28/30, 93%) and found it helpful and likely to change their purchase across various food categories and at checkout. Retail Online Shopping Assistant's reminders and suggestions could reduce less healthy shopping habits and diversify food options. Participants desired dynamic suggestions and help with various health conditions. Participants preferred a racially inclusive, approachable, cartoon-like, and clinically dressed character. CONCLUSIONS AND IMPLICATIONS: This formative study suggests ROSA could be a beneficial tool for facilitating healthy online grocery shopping among rural shoppers. Future research should investigate the impact of ROSA on dietary behaviors further.

An Adaptive Behavioral Intervention for Weight Loss Management: A Randomized Clinical Trial.

Importance: Lifestyle interventions for weight loss are difficult to implement in clinical practice. Self-managed mobile health implementations without or with added support after unsuccessful weight loss attempts could offer effective population-level obesity management. Objective: To test whether a wireless feedback system (WFS) yields noninferior weight loss vs WFS plus telephone coaching and whether participants who do not respond to initial treatment achieve greater weight loss with more vs less vigorous step-up interventions. Design, Setting, and Participants: In this noninferiority randomized trial, 400 adults aged 18 to 60 years with a body mass index of 27 to 45 were randomized in a 1:1 ratio to undergo 3 months of treatment initially with WFS or WFS plus coaching at a US academic medical center between June 2017 and March 2021. Participants attaining suboptimal weight loss were rerandomized to undergo modest or vigorous step-up intervention. Interventions: The WFS included a Wi-Fi activity tracker and scale transmitting data to a smartphone app to provide daily feedback on progress in lifestyle change and weight loss, and WFS plus coaching added 12 weekly 10- to 15-minute supportive coaching calls delivered by bachelor's degree-level health promotionists viewing participants' self-monitoring data on a dashboard; step-up interventions included supportive messaging via mobile device screen notifications (app-based screen alerts) without or with coaching or powdered meal replacement. Participants and staff were unblinded and outcome assessors were blinded to treatment randomization. Main Outcomes and Measures: The primary outcome was the between-group difference in 6-month weight change, with the noninferiority margin defined as a difference in weight change of -2.5 kg; secondary outcomes included between-group differences for all participants in weight change at 3 and 12 months and between-group 6-month weight change difference among nonresponders exposed to modest vs vigorous step-up interventions. Results: Among 400 participants (mean [SD] age, 40.5 [11.2] years; 305 [76.3%] women; 81 participants were Black and 266 were White; mean [SD] body mass index, 34.4 [4.3]) randomized to undergo WFS (n = 199) vs WFS plus coaching (n = 201), outcome data were available for 342 participants (85.5%) at 6 months. Six-month weight loss was -2.8 kg (95% CI, -3.5 to -2.0) for the WFS group and -4.8 kg (95% CI, -5.5 to -4.1) for participants in the WFS plus coaching group (difference in weight change, -2.0 kg [90% CI, -2.9 to -1.1]; P < .001); the 90% CI included the noninferiority margin of -2.5 kg. Weight change differences were comparable at 3 and 12 months and, among nonresponders, at 6 months, with no difference by step-up therapy. Conclusions and Relevance: A wireless feedback system (Wi-Fi activity tracker and scale with smartphone app to provide daily feedback) was not noninferior to the same system with added coaching. Continued efforts are needed to identify strategies for weight loss management and to accurately select interventions for different individuals to achieve weight loss goals. Trial Registration: ClinicalTrials.gov Identifier: NCT02997943.

Reversible male contraception by targeted inhibition of serine/threonine kinase 33.

Men or mice with homozygous serine/threonine kinase 33 (STK33) mutations are sterile owing to defective sperm morphology and motility. To chemically evaluate STK33 for male contraception with STK33-specific inhibitors, we screened our multibillion-compound collection of DNA-encoded chemical libraries, uncovered potent STK33-specific inhibitors, determined the STK33 kinase domain structure bound with a truncated hit CDD-2211, and generated an optimized hit CDD-2807 that demonstrates nanomolar cellular potency (half-maximal inhibitory concentration = 9.2 nanomolar) and favorable metabolic stability. In mice, CDD-2807 exhibited no toxicity, efficiently crossed the blood-testis barrier, did not accumulate in brain, and induced a reversible contraceptive effect that phenocopied genetic STK33 perturbations without altering testis size. Thus, STK33 is a chemically validated, nonhormonal contraceptive target, and CDD-2807 is an effective tool compound.

Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage.

BACKGROUND: Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known. METHODS: In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes, according to patients' assessment) at 180 days, with a prespecified threshold for posterior probability of superiority of 0.975 or higher. The trial included rules for adaptation of enrollment criteria on the basis of hemorrhage location. A primary safety end point was death within 30 days after enrollment. RESULTS: A total of 300 patients were enrolled, of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages. After 175 patients had been enrolled, an adaptation rule was triggered, and only persons with lobar hemorrhages were enrolled. The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981). The mean between-group difference was 0.127 (95% Bayesian credible interval, 0.035 to 0.219) among patients with lobar hemorrhages and -0.013 (95% Bayesian credible interval, -0.147 to 0.116) among those with anterior basal ganglia hemorrhages. The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group. Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration. CONCLUSIONS: Among patients in whom surgery could be performed within 24 hours after an acute intracerebral hemorrhage, minimally invasive hematoma evacuation resulted in better functional outcomes at 180 days than those with guideline-based medical management. The effect of surgery appeared to be attributable to intervention for lobar hemorrhages. (Funded by Nico; ENRICH ClinicalTrials.gov number, NCT02880878.).

Menke-Hennekam syndrome; delineation of domain-specific subtypes with distinct clinical and DNA methylation profiles.

CREB-binding protein (CBP, encoded by CREBBP) and its paralog E1A-associated protein (p300, encoded by EP300) are involved in histone acetylation and transcriptional regulation. Variants that produce a null allele or disrupt the catalytic domain of either protein cause Rubinstein-Taybi syndrome (RSTS), while pathogenic missense and in-frame indel variants in parts of exons 30 and 31 cause phenotypes recently described as Menke-Hennekam syndrome (MKHK). To distinguish MKHK subtypes and define their characteristics, molecular and extended clinical data on 82 individuals (54 unpublished) with variants affecting CBP (n = 71) or p300 (n = 11) (NP_004371.2 residues 1,705-1,875 and NP_001420.2 residues 1,668-1,833, respectively) were summarized. Additionally, genome-wide DNA methylation profiles were assessed in DNA extracted from whole peripheral blood from 54 individuals. Most variants clustered closely around the zinc-binding residues of two zinc-finger domains (ZZ and TAZ2) and within the first α helix of the fourth intrinsically disordered linker (ID4) of CBP/p300. Domain-specific methylation profiles were discerned for the ZZ domain in CBP/p300 (found in nine out of 10 tested individuals) and TAZ2 domain in CBP (in 14 out of 20), while a domain-specific diagnostic episignature was refined for the ID4 domain in CBP/p300 (in 21 out of 21). Phenotypes including intellectual disability of varying degree and distinct physical features were defined for each of the regions. These findings demonstrate existence of at least three MKHK subtypes, which are domain specific (MKHK-ZZ, MKHK-TAZ2, and MKHK-ID4) rather than gene specific (CREBBP/EP300). DNA methylation episignatures enable stratification of molecular pathophysiologic entities within a gene or across a family of paralogous genes.

Potential of Pinus radiata, Eucalyptus globulus and Acacia dealbata for the long-term phytostabilization of copper mine tailings.

Many contaminated tailings throughout the world cause environmental and human-health related problems due to air and water drift. Tailing phytostabilization is a promising solution, but only certain plant species may tolerate and grow in these contaminated areas. We analyzed the chemical properties of a vegetated and unvegetated area in a tailing site in Central Chile. In addition, in the vegetated area we analyzed the metals content of roots, stems, and foliage in 41-years old plantations of Pinus radiata, Acacia dealbata, and Eucalyptus globulus (the only three species that survived from a total of 34 species planted), and determined height (H), and diameter at breast height (DBH). The results indicated that, except for pH, Se, Pb, and organic matter, all components (nutrients and metals) were two- to three- fold lower in the vegetated tailing compared to that of the unvegetated tailing. The analysis of plant tissues indicated that Cu was higher in the roots of P. radiata (2,073 mg kg-1) and lower in the stems of the same species (4.1 mg kg-1). However, the ability to take up and transport Cu to the shoots was higher in A. dealbata and lower in P. radiata (bioaccumulation factor of 0.19 and 0.06, respectively).

Here we present results for the first long-term phytostabilization project of copper mine tailings in Chile. From the 34 native and exotic species established in 1980 in a mine tailing disposal site with 1,000 mg Cu kg⁻¹, only the exotic Pinus radiata, Acacia dealbata and Eucalyptus globulus were able to survive and adapt to the tailing conditions the last 41 years. This corroborates their potential for the future phytostabilization of copper mine wastes.

Analgesia Administration by Sex Among Pediatric Emergency Department Patients with Abdominal Pain.

Background: There is conflicting data about sex-based differences in the treatment of acute pain in the ED. Little is known about sex-based disparities in analgesia in pediatric ED patients. Objectives: Our objective was to determine whether analgesic administration rates differ between female and male pediatric patients presenting to the ED with abdominal pain. Methods: We conducted a retrospective cohort study of ED patients 5-21 years old with abdominal pain between 6/1/19 and 6/30/21. The primary outcome was receipt of any analgesia, and secondary outcomes were receipt of opioid analgesia and time to receipt of analgesia. Multivariable regression models were fitted for each outcome. Results: We studied 1,087 patients; 681 (63%) were female with a median age of 17 years (IQR 13, 19) and 406 (37%) were male with a median age of 14 years (IQR 9, 18). 371 female patients (55%) and 180 male patients (44%) received any analgesia. 132 female patients (19%) and 83 male patients (20%) received opioid analgesia. In multivariate analyses, female patients were equally likely to receive any analgesia (OR 1.30, 95% CI 0.97 - 1.74, p = 0.07), but time to analgesia was 14% longer (GMR 1.14, 95% CI 1.00 - 1.29, p = 0.04). Non-White patients were 32% less likely to receive opioids (OR 0.68, 95% CI 0.47 - 0.97, p = 0.04). Conclusions: Female pediatric ED patients were equally likely to receive any analgesia as male patients, but their time to analgesia was longer. Non-White patients were less likely to receive opioid analgesia than White patients.