Characterization of Awareness and Depth of Blockade During Neuromuscular Blockade Infusions in Critically Ill Children.

OBJECTIVE: The Society of Critical Care Medicine released the first guideline for the prevention and -management of pain, agitation, neuromuscular blockade, and delirium in critically ill pediatric patients but offered conditional recommendations for sedation practices and monitoring during neuromuscular blockade. This study aimed to characterize sedation practices, patient awareness, and depth of blockade with neuromuscular blocking agent (NMBA) infusion administration in a single pediatric and cardiac intensive care unit. METHODS: This retrospective chart review of critically ill pediatric patients queried orders for continuous infusion NMBA. Analgosedation agent(s), dose, and dose changes were assessed, along with depth of blockade monitoring via Train of Four (TOF) and awareness via Richmond Agitation and Sedation Scale (RASS). RESULTS: Thirty-one patients were included, of which 27 (87%) had a documented sedation agent infusing at time of NMBA initiation and 17 patients (54%) were receiving analgesia. The most common agents used were rocuronium (n = 28), dexmedetomidine (n = 23), and morphine (n = 14). RASS scores were captured in all patients; however, 9 patients (29%) had recorded positive scores and 1 patient (3%) never achieved negative scores. TOF was only captured for 11 patients (35%), with majority of the scores being 0 or 4. CONCLUSIONS: Majority of the study population did not receive recommended depth of blockade monitoring via TOF. Similarly, RASS scores were not consistent with deep sedation in half of the patients. The common use of dexmedetomidine as a single sedation agent calls into question the appropriateness of current sedation practices during NMBA continuous infusions.

Structural and mechanistic diversity in p53-mediated regulation of organismal longevity across taxonomical orders.

The accumulation of senescent cells induces several aging phenotypes, and the p53 tumor suppressor protein regulates one of the two known cellular senescence pathways. p53's regulation of senescence is however not clear. For example, p53 deficiency in some mice has been shown to rescue premature aging while others display significant aging phenotype when p53-deficient. This study seeks to elucidate, structurally and mechanistically, p53's roles in longevity. Through a relative evolutionary scoring (RES) algorithm, we quantify the level of evolutionary change in the residues of p53 across organisms of varying average lifespans in six taxonomic orders. Secondly, we used PEPPI to assess the likelihood of interaction between p53-or p53-linked proteins-and known senescence-regulating proteins across organisms in the orders Primates and Perciformes. Our RES algorithm found variations in the alignments within and across orders, suggesting that mechanisms of p53-mediated regulation of longevity may vary. PEPPI results suggest that longer-lived species may have evolved to regulate induction and inhibition of cellular senescence better than their shorter-lived counterparts. With experimental verification, these predictions could help elucidate the mechanisms of p53-mediated cellular senescence, ultimately clarifying our understanding of p53's connection to aging in a multiple-species context. Author summary: The p53 tumor suppressor protein protects our genome from cancers by repairing DNA damage, regulating cell death and/or pushing cells to a state where they become permanently unable to divide (known as cellular senescence). An accumulation of senescent cells produces various molecular features of aging in both mouse and human cellular models-thus linking p53 to the aging process. However, the molecular mechanism by which p53 regulates aging and its structural implications on this regulation are not clear. In this study, we assessed quantitatively the evolutionary differences in p53 sequences of organisms across several taxonomical orders to determine if there is a relationship between average lifespan and sequence evolution. In addition, we used a protein-protein interaction tool to assess the likelihood of interaction between p53, or p53-associated protein, and various senescence-associated proteins across organisms of various lifespans in two taxonomic orders: Primates and Perciformes. An elucidation of p53 structural difference and mechanistic proteomic network linked to p53 regulation of cellular senescence could advance therapeutics targeting abnormal aging.

Amorphous TiO2nano-coating on stainless steel to improve its biological response.

This study delves into the potential of amorphous titanium oxide (aTiO2) nano-coating to enhance various critical aspects of non-Ti-based metallic orthopedic implants. These implants, such as medical-grade stainless steel (SS), are widely used for orthopedic devices that demand high strength and durability. The aTiO2nano-coating, deposited via magnetron sputtering, is a unique attempt to improve the osteogenesis, the inflammatory response, and to reduce bacterial colonization on SS substrates. The study characterized the nanocoated surfaces (SS-a TiO2) in topography, roughness, wettability, and chemical composition. Comparative samples included uncoated SS and sandblasted/acid-etched Ti substrates (Ti). The biological effects were assessed using human mesenchymal stem cells (MSCs) and primary murine macrophages. Bacterial tests were carried out with two aerobic pathogens (S. aureusandS. epidermidis) and an anaerobic bacterial consortium representing an oral dental biofilm. Results from this study provide strong evidence of the positive effects of the aTiO2nano-coating on SS surfaces. The coating enhanced MSC osteoblastic differentiation and exhibited a response similar to that observed on Ti surfaces. Macrophages cultured on aTiO2nano-coating and Ti surfaces showed comparable anti-inflammatory phenotypes. Most significantly, a reduction in bacterial colonization across tested species was observed compared to uncoated SS substrates, further supporting the potential of aTiO2nano-coating in biomedical applications. The findings underscore the potential of magnetron-sputtering deposition of aTiO2nano-coating on non-Ti metallic surfaces such as medical-grade SS as a viable strategy to enhance osteoinductive factors and decrease pathogenic bacterial adhesion. This could significantly improve the performance of metallic-based biomedical devices beyond titanium.

Healthcare resource utilisation and suicidal ideation amongst adolescents in the US with posttraumatic stress disorder, major depressive disorder, and substance use disorders using electronic health records.

BACKGROUND: While PTSD is commonly associated with multiple comorbidities, studies have yet to quantify the impact of these comorbidities on key clinical outcomes and HCRU. This study explored risks of emergency room (ER) visits, inpatient admissions (IA), suicidal ideation (SI), and treatment follow-up duration (FU), amongst PTSD patients with comorbid MDD and/or SUD. METHODS: Using real-world data (RWD) generated by electronic health records accessed from the NeuroBlu database, a cohort of adolescent patients (12-17 yrs) was examined over a one-year study period following PTSD diagnosis. RESULTS: 5794 patients were included in the cohort. Compared to patients with only PTSD (n = 3061), those with comorbid MDD (n = 1820) had greater odds of ER (4.5 times), IA (1.6 times), and FU (4.3 times). Those with comorbid SUD (n = 653) had greater odds of IA (4.5 times), shorter FU (34 days), and lower odds of ER (0.5 times). Both comorbidities (n = 260) had greater odds of ER (3.8 times), IA (2.6 times), SI (3.6 times), and shorter FU (12 days). LIMITATIONS: These RWD had a high proportion of missingness. Health records of patients who changed service providers could not be accounted for in this study. CONCLUSIONS: Both MDD and SUD substantially elevated the risk of HCRU and suicidal ideation for PTSD patients.

Factorial Trial to Optimize an Internet-Delivered Intervention for Sexual Health After Breast Cancer: Protocol for the WF-2202 Sexual Health and Intimacy Enhancement (SHINE) Trial.

BACKGROUND: Although most survivors of breast cancer report substantial sexual concerns following treatment, few receive support for these concerns. Delivering sexual health care to survivors of breast cancer via the internet could overcome many of the barriers to in-person treatment. Even when delivered remotely, survivor time constraints remain a leading barrier to sexual health intervention uptake. OBJECTIVE: Guided by the multiphase optimization strategy methodological framework, the primary objective of this study is to identify the most efficient internet-delivered sexual health intervention package that is expected to provide survivors of breast cancer the greatest benefit with the fewest (and least-intensive) intervention components. This study aims to determine how intervention components work (mediators) and for whom they work best (moderators). METHODS: Partnered, posttreatment adult female survivors of breast cancer (N=320) experiencing at least 1 bothersome sexual symptom (ie, pain with sex, vaginal dryness, low sexual desire, and difficulty with orgasm) related to their breast cancer treatment will be enrolled. Clinic-based recruitment will be conducted via the Wake Forest National Cancer Institute Community Oncology Research Program (NCORP) Research Base. Participants will be randomly assigned to 1 of 16 combinations of four intervention components with two levels each in this factorial trial: (1) psychoeducation about cancer-related sexual morbidity (receive either enhanced vs standard versions); (2) communication skills training for discussing concerns with health care providers (received vs not received); (3) communication skills training for discussing concerns with a partner (received vs not received); and (4) intimacy promotion skills training (received vs not received). Cores will be fully automated and implemented using a robust internet intervention platform with highly engaging elements such as animation, video, and automated email prompts. Survivors will complete web-based assessments at baseline (prerandomization time point) and again at 12 and 24 weeks later. The primary study aim will be achieved through a decision-making process based on systematically evaluating the main and interaction effects of components on sexual distress (Female Sexual Distress Scale-Desire, Arousal, Orgasm) and sexual functioning (Female Sexual Function Index) using a generalized linear model approach to ANOVA with effect coding. Mediation analyses will be conducted through a structural equation modeling approach, and moderation analyses will be conducted by extending the generalized linear model to include interaction effects. RESULTS: This protocol has been reviewed and approved by the National Cancer Institute Central Institutional Review Board. Data collection is planned to begin in March 2024 and conclude in 2027. CONCLUSIONS: By identifying the combination of the fewest and least-intensive intervention components likely to provide survivors of breast cancer the greatest sexual health benefit, this study will result in the first internet intervention that is optimized for maximum impact on the undertreated, prevalent, and distressing problem of breast cancer-related sexual morbidity. TRIAL REGISTRATION: ClinicalTrials.gov NCT06216574; https://clinicaltrials.gov/study/NCT06216574. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/57781.

Multiple metal exposures associate with higher amyotrophic lateral sclerosis risk and mortality independent of genetic risk and correlate to self-reported exposures: a case-control study.

BACKGROUND: The pathogenesis of amyotrophic lateral sclerosis (ALS) involves both genetic and environmental factors. This study investigates associations between metal measures in plasma and urine, ALS risk and survival and exposure sources. METHODS: Participants with and without ALS from Michigan provided plasma and urine samples for metal measurement via inductively coupled plasma mass spectrometry. ORs and HRs for each metal were computed using risk and survival models. Environmental risk scores (ERS) were created to evaluate the association between exposure mixtures and ALS risk and survival and exposure source. ALS (ALS-PGS) and metal (metal-PGS) polygenic risk scores were constructed from an independent genome-wide association study and relevant literature-selected single-nucleotide polymorphisms. RESULTS: Plasma and urine samples from 454 ALS and 294 control participants were analysed. Elevated levels of individual metals, including copper, selenium and zinc, significantly associated with ALS risk and survival. ERS representing metal mixtures strongly associated with ALS risk (plasma, OR=2.95, CI=2.38-3.62, p<0.001; urine, OR=3.10, CI=2.43-3.97, p<0.001) and poorer ALS survival (plasma, HR=1.37, CI=1.20-1.58, p<0.001; urine, HR=1.44, CI=1.23-1.67, p<0.001). Addition of the ALS-PGS or metal-PGS did not alter the significance of metals with ALS risk and survival. Occupations with high potential of metal exposure associated with elevated ERS. Additionally, occupational and non-occupational metal exposures were associated with measured plasma and urine metals. CONCLUSION: Metals in plasma and urine associated with increased ALS risk and reduced survival, independent of genetic risk, and correlated with occupational and non-occupational metal exposures. These data underscore the significance of metal exposure in ALS risk and progression.

The acute hypoalgesic effects of active head-mounted display virtual reality games.

The purpose of this study was to determine: (1) whether physically active virtual reality (VR) games exert an acute hypoaglesic effect on the thigh and bicep compared to a non-active VR game and an exercise only condition matched for exercise intensity in healthy individuals, and (2) whether movement variables during gameplay are associated with the hypoalgesic effect of the games. Twenty young adults completed five separate study sessions, with each session devoted to playing one head-mounted display VR game or stationary cycling for 15 minutes. The games included Holopoint at level 2 and level 3, Hot Squat, and Relax Walk. Pressure pain thresholds at the thigh and bicep were measured pre and post VR gameplay and cycling. Participants wore a heart rate monitor and accelerometers on the wrist and thigh during play to measure the intensity and quantity of movement. Repeated measures ANOVAs revealed that pressure pain thresholds on the bicep increased from pre to posttest for each condition. The results also revealed that pressure pain thresholds on the thigh increased only for the conditions eliciting the greatest cardiovascular response, which included Holopoint at level 3, Hot Squat, and cycling. Bivariate correlations indicated that moderate to vigorous physical activity of the thigh was associated with pain reduction at the thigh during Holopoint. These results revealed that active VR games and exercise exerted a more widespread hypoalgesic effect compared to the non-active VR game, which was likely driven in part by the intensity and quantity of movement during gameplay.

Nationally endorsed learning objectives to improve course design in introductory biology.

Introductory biology for majors is one of the most consequential courses in STEM, with annual enrollments of several hundred thousand students in the United States alone. To support increased student success and meet current and projected needs for qualified STEM professionals, it will be crucial to redesign majors biology by using explicit learning objectives (LOs) that can be aligned with assessments and active learning exercises. When a course is designed in this way, students have opportunities for the practice and support they need to learn, and instructors can collect the evidence they need to evaluate whether students have mastered key concepts and skills. Following an iterative process of review, revision, and evaluation, which included input from over 800 biology instructors around the country, we produced a nationally endorsed set of lesson-level LOs for a year-long introductory biology for major's course. These LOs are granular enough to support individual class sessions and provide instructors with a framework for course design that is directly connected to the broad themes in Vision and Change and the general statements in the BioCore and BioSkills Guides. Instructors can implement backward course design by aligning these community endorsed LOs with daily and weekly learning activities and with formative and summative assessments.

Safety and efficacy of PfSPZ Vaccine against malaria in healthy adults and women anticipating pregnancy in Mali: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials.

BACKGROUND: Plasmodium falciparum parasitaemia during pregnancy causes maternal, fetal, and infant mortality. Poor pregnancy outcomes are related to blood-stage parasite sequestration and the ensuing inflammatory response in the placenta, which decreases over successive pregnancies. A radiation-attenuated, non-replicating, whole-organism vaccine based on P falciparum sporozoites (PfSPZ Vaccine) has shown efficacy at preventing infection in African adults. Here, we aimed to examine vaccine safety and efficacy of the PfSPZ Vaccine in adults and women who anticipated conception. METHODS: Two randomised, double-blind, placebo-controlled trials (phase 1 MLSPZV3 and phase 2 MLSPZV4) were conducted at a clinical research centre in Mali. MLSPZV3 included adults aged 18-35 years and MLSPZV4 included non-pregnant women aged 18-38 years who anticipated conception within a year of enrolment. In MLSPZV3, participants were stratified by village and randomly assigned (2:1) using block randomisation to receive three doses of 9 × 105 PfSPZ Vaccine or saline placebo at weeks 0, 1, and 4 (4-week schedule) or at weeks 0, 8, and 16 (16-week schedule) and a booster dose around 1 year later. In MLSPZV4, women received presumptive artemether-lumefantrine twice per day for 3 days 2 weeks before dose one and were randomly assigned (1:1:1) using block randomisation to receive three doses of 9 × 105 or 1·8 × 106 PfSPZ Vaccine or saline placebo all administered at weeks 0, 1, and 4 (4-week schedule). Participants in both studies received artemether-lumefantrine 2 weeks before dose three and additionally 2 weeks before dose four (booster dose) in MLSPZV3. Investigators and participants were masked to group assignment. The primary outcome, assessed in the as-treated population, was PfSPZ Vaccine safety and tolerability within 7 days after each dose. The secondary outcome, assessed in the modified intention-to-treat population, was vaccine efficacy against P falciparum parasitaemia (defined as the time-to-first positive blood smear) from dose three until the end of transmission season. In exploratory analyses, MLSPZV4 evaluated incidence of maternal obstetric and neonatal outcomes as safety outcomes, and vaccine efficacy against P falciparum parasitaemia during pregnancy (defined as time-to-first positive blood smear post-conception). In MLSPZV4, women were followed at least once a month with human chorionic gonadotropin testing, and those who became pregnant received standard of care (including intermittent presumptive sulfadoxine-pyrimethamine antimalarial drugs after the first trimester) during routine antenatal visits. These studies are registered with ClinicalTrials.gov, NCT03510481 and NCT03989102. FINDINGS: Participants were enrolled for vaccination during the onset of malaria seasons for two sequential studies conducted from 2018 to 2019 for MLSPZV3 and from 2019 to 2021 for MLSPZV4, with follow-up during malaria seasons across 2 years. In MLSPZV3, 478 adults were assessed for eligibility, of whom 220 were enrolled between May 30 and June 12, 2018, and then between Aug 13 and Aug 18, 2018, and 210 received dose one. 66 (96%) of 69 participants who received the 16-week schedule and 68 (97%) of 70 who received the 4-week schedule of the 9 × 105 PfSPZ Vaccine and 70 (99%) of 71 who received saline completed all three doses in year 1. In MLSPZV4, 407 women were assessed for eligibility, of whom 324 were enrolled from July 3 to July 27, 2019, and 320 received dose one of presumptive artemether-lumefantrine. 300 women were randomly assigned with 100 per group (PfSPZ Vaccine 9 × 105, 1·8 × 106, or saline) receiving dose one. First trimester miscarriages were the most commonly reported serious adverse event but occurred at a similar rate across study groups (eight [15%] of 54 with 9 × 105 PfSPZ Vaccine, 12 [21%] of 58 with 1·8 × 106 PfSPZ Vaccine, and five [12%] of 43 with saline). One unrelated maternal death occurred 425 days after the last vaccine dose in the 1·8 × 106 PfSPZ Vaccine group due to peritonitis shortly after childbirth. Most related adverse events reported in MLSPZV3 and MLSPZV4 were mild (grade 1) and frequency of adverse events in the PfSPZ Vaccine groups did not differ from that in the saline group. Two unrelated serious adverse events occurred in MLSPZV3 (one participant had appendicitis in the 9 × 105 PfSPZ Vaccine group and the other in the saline group died due to a road traffic accident). In MLSPZV3, the 9 × 105 PfSPZ Vaccine did not show vaccine efficacy against parasitaemia with the 4-week (27% [95% CI -18 to 55] in year 1 and 42% [-5 to 68] in year 2) and 16-week schedules (16% [-34 to 48] in year 1 and -14% [-95 to 33] in year 2); efficacies were similar or worse against clinical malaria compared with saline. In MLSPZV4, the PfSPZ Vaccine showed significant efficacy against parasitaemia at doses 9 × 105 (41% [15 to 59]; p=0·0069 in year 1 and 61% [36 to 77]; p=0·0011 in year 2) and 1·8 × 106 (54% [34 to 69]; p<0·0001 in year 1 and 45% [13 to 65]; p=0·029 in year 2); and against clinical malaria at doses 9 × 105 (47% [20 to 65]; p=0·0045 in year 1 and 56% [22 to 75]; p=0·0081 in year 2) and 1·8 × 106 (48% [22 to 65]; p=0·0013 in year 1 and 40% [2 to 64]; p=0·069 in year 2). Vaccine efficacy against post-conception P falciparum parasitaemia during first pregnancies that arose in the 2-year follow-up was 57% (14 to 78; p=0·017) in the 9 × 105 PfSPZ Vaccine group versus 49% (3 to 73; p=0·042) in the 1·8 × 106 PfSPZ Vaccine group. Among 55 women who became pregnant within 24 weeks after dose three, vaccine efficacy against parasitaemia was 65% (23 to 84; p=0·0088) with the 9 × 105 PfSPZ Vaccine and 86% (64 to 94; p<0·0001) with the 1·8 × 106 PfSPZ Vaccine. When combined in a post-hoc analysis, women in the PfSPZ Vaccine groups had a non-significantly reduced time-to-first pregnancy after dose one compared with those in the saline group (log-rank test p=0·056). Exploratory maternal obstetric and neonatal outcomes did not differ significantly between vaccine groups and saline. INTERPRETATION: PfSPZ Vaccine was safe and well tolerated in adults in Mali. The 9 × 105 and 1·8 × 106 doses of PfSPZ Vaccine administered as per the 4-week schedule, which incorporated presumptive antimalarial treatment before the first vaccine dose, showed significant efficacy against P falciparum parasitaemia and clinical malaria for two malaria transmission seasons in women of childbearing age and against pregnancy malaria. PfSPZ Vaccine without presumptive antimalarial treatment before the first vaccine dose did not show efficacy. FUNDING: National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Sanaria.

Interdisciplinary provider visits attenuate relationship between patient concerns and distress in older adults with cancer.

PURPOSE: This study examined the relationship between multidimensional patient concerns and anxiety and depression in a national sample of older adults with cancer (OACs ≥ 65 years) and the buffering effect of visiting providers across disciplines (e.g., oncology, allied health, primary care, mental health) on these relationships. METHODS: Participants completed a cross-sectional survey through the Cancer Support Community's Cancer Experience Registry (CER), an online community-based research initiative. Eligible participants were 65 years and older and diagnosed with cancer in the past five years. Participants completed self-report measures of (1) the severity of their concerns across multiple domains, (2) anxiety and depression, and (3) whether they received care for "symptoms and side effects" from various providers. RESULTS: The sample consisted of 277 OACs; 45% endorsed elevated anxiety and 31% endorsed elevated depression. The most severe concerns were in the domains of body image and healthy lifestyle and symptom burden and impact. More severe concerns were associated with higher levels of anxiety and depression. The relationship between concern severity and distress was weaker in OACs who saw a palliative care, mental health, physical or occupational therapy provider, pharmacist, or primary care provider relative to OACs who did not. A visit with an oncology provider did not moderate most relationships between concerns and distress. CONCLUSIONS: The relationship between OACs' concerns and distress was attenuated by treatment with a specialty provider. Interdisciplinary team care may be a vital component of comprehensive patient-centered care for OACs.

Addressing emerging issues in entomology: 2023 student debates.

The Entomological Society of America (ESA) Student Debates is an annual student competition at the ESA Annual Meeting organized by Student Debates Subcommittee (SDS) members of the ESA Student Affairs Committee. In conjunction with the 2023 ESA Annual Meeting theme, 'Insects and influence: Advancing entomology's impact on people and policy', the theme of this year's student debate was 'Addressing emerging issues in entomology'. With the aid of ESA membership, the SDS selected the following debate topics: (1) Should disclosure of artificial intelligence large language models in scientific writing always be required? and (2) Is it more important to prioritize honey bee or native pollinator health for long-term food security within North America? Four student teams from across the nation, composed of 3-5 student members and a professional advisor, were assigned a topic and stance. Over the course of 5 months, all team members researched and prepared for their assigned topic before debating live with an opposing team at the 2023 ESA Annual Meeting in National Harbor, Maryland. SDS members additionally prepared and presented introductions for each debate topic to provide unbiased backgrounds to the judges and audience for context in assessing teams' arguments. The result was an engaging discussion between our teams, judges, and audience members on emerging issues facing entomology and its impact on people and policy, such as scientific communication and food security, that brought attention to the complexities involved when debating topics concerning insects and influence.

A Comprehensive Protocol for the Collection, Differentiation, Cryopreservation, and Resuscitation of Primary Murine Bone Marrow Derived Macrophages (BMDM).

BACKGROUND: The field of immunology has undoubtedly benefited from the in vitro use of cell lines for immunological studies; however, due to the "immortal" nature of many cell lines, they are not always the best model. Thus, direct collection and culture of primary cells from model organisms is a solution that many researchers utilize. To the best of our knowledge, there is not a singular protocol which encompasses the entire process of bone marrow cell collection through cryopreservation and resuscitation of cells from a murine model. METHODS: Bone marrow cells were collected from mice with a C57BL6 genetic background. Cells were differentiated using L929 conditioned media. Cells were assessed using a combination of microscopy, differential staining, immunocytochemistry, and trypan blue. Results: Primary murine BMDMs that underwent cryopreservation followed by resuscitation retained a high degree of viability. Furthermore, these BMDMs retained on overall ability to clear S. aureus. RESULTS: Primary murine BMDMs that underwent cryopreservation followed by resuscitation retained a high degree of viability. Furthermore, these BMDMs retained on overall ability to clear S. aureus. CONCLUSION: Crypopreserved and resuscitated primary murine BMDMs were viable and retained their pverall S. aureus clearance ability.

Microbial intestinal dysbiosis drives long-term allergic susceptibility by sculpting an ILC2-B1 cell-innate IgE axis.

BACKGROUND: The abundance and diversity of intestinal commensal bacteria influence systemic immunity with impact on disease susceptibility and severity. For example, loss of short chain fatty acid (SCFA)-fermenting bacteria in early life (humans and mice) is associated with enhanced type 2 immune responses in peripheral tissues including the lung. OBJECTIVE: Our goal was to reveal the microbiome-dependent cellular and molecular mechanisms driving enhanced susceptibility to type 2 allergic lung disease. METHODS: We used low-dose vancomycin to selectively deplete SCFA-fermenting bacteria in wild type mice (Vanc-dys mice). We then examined the frequency and activation status of innate and adaptive immune cell lineages with and without SCFA supplementation. Finally, we used ILC2-deficient and signal transducer and activator of transcription 6 (STAT6)-deficient transgenic mouse strains to delineate the cellular and cytokine pathways leading to enhanced allergic disease susceptibility. RESULTS: Vanc-dys mice exhibit a 2-fold increase in lung ILC2 primed to produce elevated levels of interleukin (IL)-2, -5 and -13. In addition, upon IL-33 treatment, Vanc-dys lung ILC2 display a novel ability to produce high levels of IL-4. These expanded and primed ILC2 drive B1 cell expansion and IL-4-dependent production of IgE that, in turn, leads to exacerbated allergic inflammation. Importantly, these enhanced lung inflammatory phenotypes in Vanc-dys mice were reversed by administration of dietary SCFA (specifically butyrate). CONCLUSION: SCFA regulate an ILC2-B1cell-IgE axis. Early-life administration of vancomycin, an antibiotic known to deplete SCFA-fermenting gut bacteria, primes and amplifies this axis and leads to a lifelong enhanced susceptibility to type 2 allergic lung disease.

Characteristics and Outcomes of Adults With Congenital Heart Disease in the Cardiac Intensive Care Unit.

Background: Little is known regarding the characteristics, treatment patterns, and outcomes in patients with adult congenital heart disease (ACHD) admitted to cardiac intensive care units (CICUs). Objectives: The authors sought to better define the contemporary epidemiology, treatment patterns, and outcomes of ACHD admissions in the CICU. Methods: The Critical Care Cardiology Trials Network is a multicenter network of CICUs in North America. Participating centers contributed prospective data from consecutive admissions during 2-month annual snapshots from 2017 to 2022. We analyzed characteristics and outcomes of admissions with ACHD compared with those without ACHD. Multivariable logistic regression was used to assess mortality in ACHD vs non-ACHD admissions. Results: Of 23,299 CICU admissions across 42 sites, there were 441 (1.9%) ACHD admissions. Shunt lesions were most common (46.1%), followed by right-sided lesions (29.5%) and complex lesions (28.7%). ACHD admissions were younger (median age 46 vs 67 years) than non-ACHD admissions. ACHD admissions were more commonly for heart failure (21.3% vs 15.7%, P < 0.001), general medical problems (15.6% vs 6.0%, P < 0.001), and atrial arrhythmias (8.6% vs 4.9%, P < 0.001). ACHD admissions had a higher median presenting Sequential Organ Failure Assessment score (5.0 vs 3.0, P < 0.001). Total hospital stay was longer for ACHD admissions (8.2 vs 5.9 days, P < 0.01), though in-hospital mortality was not different (12.7% vs 13.6%; age- and sex-adjusted OR: 1.19 [95% CI: 0.89-1.59], P = 0.239). Conclusions: This study illustrates the unique aspects of the ACHD CICU admission. Further investigation into the best approach to manage specific ACHD-related CICU admissions, such as cardiogenic shock and acute respiratory failure, is warranted.

Broaching body size and sizeism: Input from specialized clinicians.

Broaching issues of identity and power with clients in the context of their mental health care is affirmed as an effective multicultural and social justice counseling skill by a growing evidence base. Considerations for broaching body size, including size difference and sizeism, with clients has not yet been studied, thus clinicians lack guidelines for facilitating these conversations. In this consensual qualitative research study, we present themes involved in broaching body topics based on our interviews with nine clinicians specialized in treating clients with eating disorders and body-related counseling concerns. Themes addressed counselor development, conceptualization of broaching, clinical-decision-making, practice, and impact of broaching body topics in session. Clinicians identified professional and personal developments they pursued and would advocate for training future clinicians to better serve clients. Descriptions of unique and shared aspects of broaching clients' intersectionality and body-size specifically depict avenues for tailoring broaching conversations. Specific examples of effective and ineffective broaching conversations, including language used and psychoeducational components, provide recommendations for practice and connect to observed impacts on the client, counselor, and counseling process.

Evaluation of an Educational Scholarship Fellowship Program for Health Professions Educators.

Introduction: Historically, the requirement to produce scholarship for advancement has challenged health professions educators heavily engaged in teaching. As biomedical scientists or healthcare practitioners, few are trained in educational scholarship, and related faculty development varies in scope and quality across institutions. Currently, there is a need for faculty development and mentoring programs to support the development of these skills. Methods: The International Association of Medical Science Educators (IAMSE) established the Medical Educator Fellowship (MEF) Program to foster health professions educational scholarship. MEF addresses the following: curriculum design, teaching methods and strategies, assessment, educational scholarship, and leadership. Participants receive mentorship and faculty development, and complete an educational scholarship project. Using a logic model, we conducted a retrospective program evaluation with data from Program records, database searches, graduate surveys, and focus groups. Results: Over 14 years, MEF graduated 61 participants with diverse terminal degrees from five continents and six academic program areas. Graduate survey responses indicated enhanced post-Program skills in all focus areas, that the majority would recommend MEF to a colleague, and that mentorship, networking, and professional development were strengths. Focus group outcomes indicated professional growth, increased confidence, and increased sense of community. Conclusion: MEF addresses health professions educators' need for faculty development and mentorship in educational scholarship. Evaluation outcomes suggest that MEF effectively enhanced perceived skills across focus areas. Similar programs are essential to support faculty who dedicate significant time to teaching. Organizations like IAMSE can demonstrate the value of educational scholarship and positively impact health professions educator careers by supporting such programs.

Single-cell investigation of lead toxicity from neurodevelopment to neurodegeneration: Current review and future opportunities.

Human exposure to the metal lead (Pb) is prevalent and associated with adverse neurodevelopmental and neurodegenerative outcomes. Pb disrupts normal brain function by inducing oxidative stress and neuroinflammation, altering cellular metabolism, and displacing essential metals. Prior studies on the molecular impacts of Pb have examined bulk tissues, which collapse information across all cell types, or in targeted cells, which are limited to cell autonomous effects. These approaches are unable to represent the complete biological implications of Pb exposure because the brain is a cooperative network of highly heterogeneous cells, with cellular diversity and proportions shifting throughout development, by brain region, and with disease. New technologies are necessary to investigate whether Pb and other environmental exposures alter cell composition in the brain and whether they cause molecular changes in a cell-type-specific manner. Cutting-edge, single-cell approaches now enable research resolving cell-type-specific effects from bulk tissues. This article reviews existing Pb neurotoxicology studies with genome-wide molecular signatures and provides a path forward for the field to implement single-cell approaches with practical recommendations.

Risk to reoffend changes over time: Improving correctional programming through progress monitoring.

Progress monitoring is integral to evidence-based practice. Correctional settings, especially the supervision of individuals who commit sexual offenses, elicit public concern; negative outcomes can be catastrophic. Using a prospective longitudinal study of 2,939 men with a history of sexual offenses undergoing community supervision, we examined different models of progress monitoring and how they should inform the assessment of risk for sexual recidivism. We found that the most recent assessment scores of the ACUTE-2007 and STABLE-2007 sexual recidivism risk tools provided the best information about reoffending risk compared to using (a) the worst period of adjustments (i.e., highest risk score), (b) the best period of adjustments (i.e., lowest risk score), or (c) a rolling average of scores. We also found that the latest STABLE-2007 scores incrementally predicted sexual recidivism beyond baseline risk as assessed by demographic and criminal history variables (Static-99R). We conclude that the risk for sexual recidivism changes over time and that community corrections is advanced by repeated assessment of dynamic (changeable) risk factors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Caregivers' Internet-Delivered Insomnia Intervention Engagement and Benefit: SHUTi-CARE Trial Primary Quantitative Analysis.

BACKGROUND: Delivering insomnia treatment by the Internet holds promise for increasing care access to family caregivers, but their ability to adhere to and benefit from such fully-automated programs has not been rigorously tested. PURPOSE: This fully-powered, single-group trial tested whether characteristics of the caregiving context influence high-intensity caregivers' engagement with and benefit from an empirically validated Internet intervention for insomnia. METHODS: At baseline, caregivers providing unpaid time- and responsibility-intensive care who reported insomnia (N = 100; age M = 52.82 [SD = 13.10], 75% non-Hispanic white, 66% ≥college degree) completed questionnaires about caregiving context and sleep, then 10 prospectively-collected online daily sleep diaries. Caregivers then received access to SHUTi (Sleep Healthy Using the Internet), which has no caregiver-specific content, for 9 weeks, followed by post-assessment (questionnaires, diaries). Engagement was tracked by the SHUTi delivery system. RESULTS: Sixty caregivers completed SHUTi, 22 initiated but did not complete SHUTi, and 18 did not initiate SHUTi. Caregivers were more likely to use SHUTi (than not use SHUTi) when their care recipient (CR) had worse functioning, and were more likely to complete SHUTi when supporting more CR activities of daily living (ADL; ps < .03). Higher caregiver guilt, more CR problem behaviors, and being bedpartners with the CR related to more improved sleep outcomes, whereas supporting more CR instrumental ADL related to less improvement (ps < .05). CONCLUSIONS: Factors associated with greater caregiving burden, including greater CR impairment and caregiving guilt, were generally associated with better engagement and outcomes. Caregivers with substantial burdens can adhere to and benefit from a fully automated insomnia program without caregiver-specific tailoring.

This study examined how family caregivers, who often have trouble sleeping due to their responsibilities, used an online insomnia treatment program. The goal was to determine if certain aspects of caregiving would influence how caregivers engage with or benefit from the program. Researchers surveyed 100 caregivers with insomnia about their caregiving situation and sleep, and caregivers also kept online sleep diaries for 10 days. Afterward, caregivers used an online insomnia program with no caregiver-specific content called Sleep Healthy Using the Internet (SHUTi) for 9 weeks. Caregivers' usage was monitored, and they repeated measures of sleep outcomes and 10 online sleep diaries. Sixty caregivers completed SHUTi, 22 partially completed the program, and 18 did not initiate the program. Caregivers who cared for individuals with more severe functional limitations were more likely to use and complete SHUTi. Additionally, caregivers experiencing more guilt and those who managed more challenging behaviors from the person they cared for tended to report greater improvements in their sleep. This study suggests that caregivers, even those with significant care responsibilities, can use and benefit from an online insomnia treatment program like SHUTi, even when it has not been specifically tailored for caregivers.