Youth and Young Adults' Knowledge and Perceptions of Risks and Benefits Regarding Cannabis Products: A Cross-Sectional Analysis of Over 1,700 Individuals.

Canada legalized the use of non-medical cannabis in 2018. This study examines youth and young adults' knowledge and perceptions of harms, benefits, and education around cannabis use since legalization. An online survey was completed by a convenience sample of 1,759 individuals aged 12-25 years living in Manitoba, Canada. Most participants (n = 1,525, 86.7%) reported receiving education on the potential effects/harms related to cannabis; the most common topics included driving and cannabis use (79.9%), the mental harms of cannabis (67.4%), and addiction and dependency (66.3%). Youth who reported using cannabis more than once (n = 1,203) were more knowledgeable about the effects of cannabis than youth who never used cannabis or used cannabis once (n = 580; mean score: 6.6 versus 5.7 out of 8, respectively; p < .001). Vaping cannabis oil was perceived as the most harmful cannabis product among all participants. Among participants with experience using cannabis, the most frequently reported benefits were relaxation, improved sleep, and enhanced enjoyment of food/music. Half of the participants reported ever being in a car with someone driving high, of which, 40% of these participants reported doing so in the last 30 days. Future tailored education is needed to address knowledge related to cannabis use among youth and young adults who use and do not use cannabis.

Pediatric urinary tract infections caused by poultry-associated Escherichia coli.

Escherichia coli is the leading cause of urinary tract infections (UTIs) in children and adults. The gastrointestinal tract is the primary reservoir of uropathogenic E. coli, which can be acquired from a variety of environmental exposures, including retail meat. In the current study, we used a novel statistical-genomic approach to estimate the proportion of pediatric UTIs caused by foodborne zoonotic E. coli strains. E. coli urine isolates were collected from DC residents aged 2 months to 17 years from the Children's National Medical Center Laboratory, 2013-2014. During the same period, E. coli isolates were collected from retail poultry products purchased from 15 sites throughout DC. A total of 52 urine and 56 poultry isolates underwent whole-genome sequencing, core genome phylogenetic analysis, and host-origin prediction by a Bayesian latent class model that incorporated data on the presence of mobile genetic elements (MGEs) among E. coli isolates from multiple vertebrate hosts. A total of 56 multilocus sequence types were identified among the isolates. Five sequence types-ST10, ST38, ST69, ST117, and ST131-were observed among both urine and poultry isolates. Using the Bayesian latent class model, we estimated that 19% (10/52) of the clinical E. coli isolates in our population were foodborne zoonotic strains. These data suggest that a substantial portion of pediatric UTIs in the Washington DC region may be caused by E. coli strains originating in food animals and likely transmitted via contaminated poultry meat.IMPORTANCEEscherichia coli UTIs are a heavy public health burden and can have long-term negative health consequences for pediatric patients. E. coli has an extremely broad host range, including humans, chickens, turkeys, pigs, and cattle. E. coli derived from food animals is a frequent contaminant of retail meat products, but little is known about the risk these strains pose to pediatric populations. Quantifying the proportion of pediatric UTIs caused by food-animal-derived E. coli, characterizing the highest-risk strains, and identifying their primary reservoir species could inform novel intervention strategies to reduce UTI burden in this vulnerable population. Our results suggest that retail poultry meat may be an important vehicle for pediatric exposure to zoonotic E. coli strains capable of causing UTIs. Vaccinating poultry against the highest-risk strains could potentially reduce poultry colonization, poultry meat contamination, and downstream pediatric infections.

Comparison of outcomes of abdominoperineal resection vs low anterior resection in very-low rectal cancer.

BACKGROUND: The management of very-low rectal cancer is one of the most challenging issues faced by general and colorectal surgeons. Many feel compelled to pursue abdominoperineal resection (APR) over low anterior resection (LAR) to optimize oncologic outcomes. This study aimed to determine differences in long-term oncologic outcomes between patients undergoing APR or LAR for very-low rectal cancer. METHODS: The United States Rectal Cancer Consortium (2010-2016) was queried for adults who underwent either APR or LAR for stage I-III rectal cancers < 5 cm from anorectal junction and met inclusion criteria. The primary outcome was disease-free survival. Secondary outcomes included overall survival, length of stay, complications, recurrence location, and perioperative factors. RESULTS: A total of 431 patients with very-low rectal cancer who underwent APR or LAR were identified; 154 (35.7%) underwent APR. The overall recurrence rate was 19.6%. The median follow-up was 42.5 months. An analysis adjusted for demographics and pathologic stage observed no difference in disease-free survival between operative types (APR-hazard ratio [HR] = 0.90, 95% CI: 0.53-1.52, P = .70). Secondary outcomes demonstrated no significant difference between operation types, including overall survival (HR = 1.29, 95% CI: 0.71-2.32, P = .39), complications (OR = 1.53, 95% CI: 0.94-2.50, P = .12), or length of stay (estimate: 0.04, SE = 0.25, P = .54). CONCLUSION: We observed no significant difference in disease-free survival or overall survival between patients undergoing APR or LAR for very-low rectal cancer. This analysis supports the treatment of very-low rectal cancer, without sphincter involvement, by either APR or LAR.

Building a growing genomic data repository for maternal and fetal health through the PING Consortium.

Background: Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Discordant outcomes among dizygotic twins could be explained by genetic susceptibly or protection. Among several well-recognized threats to the developing brain, Zika is a mosquito-borne, positive-stranded RNA virus that was originally isolated in Uganda and spread to cause epidemics in Africa, Asia, and the Americas. In the Americas, the virus caused congenital Zika syndrome and a multitude of neurodevelopmental disorders. As of now, there is no preventative treatment or cure for the adverse outcomes caused by prenatal Zika infection. The Prenatal Infection and Neurodevelopmental Genetics (PING) Consortium was initiated in 2016 to identify factors modulating prenatal brain injury and postnatal neurodevelopmental outcomes for Zika and other prenatal viral infections. Methods: The Consortium has pooled information from eight multi-site studies conducted at 23 research centers in six countries to build a growing clinical and genomic data repository. This repository is being mined to search for modifiers of virally induced brain injury and developmental outcomes. Multilateral partnerships include commitments with Children's National Hospital (USA), Instituto Nacional de Salud (Colombia), the Natural History of Zika Virus Infection in Gestation program (Brazil), and Zika Instituto Fernandes Figueira (Brazil), in addition to the Centers for Disease Control and Prevention and the National Institutes of Health. Discussion: Our goal in bringing together these sets of patient data was to test the hypothesis that personal and populational genetic differences affect the severity of brain injury after a prenatal viral infection and modify neurodevelopmental outcomes. We have enrolled 4,102 mothers and 3,877 infants with 3,063 biological samples and clinical data covering over 80 phenotypic fields and 5,000 variables. There were several notable challenges in bringing together cohorts enrolled in different studies, including variability in the timepoints evaluated and the collected clinical data and biospecimens. Thus far, we have performed whole exome sequencing on 1,226 participants. Here, we present the Consortium's formation and the overarching study design. We began our investigation with prenatal Zika infection with the goal of applying this knowledge to other prenatal infections and exposures that can affect brain development.

Investigating visual preferences of clinical mechanical anesthetic vibration: a cross-sectional image survey.

While mechanical vibration lessens discomfort associated with injection site pain (ISP), many local anesthetic injectors (LAIs) do not use vibratory anesthetic devices (VADs). Injector preference of vibration device is influenced by functional concerns, but qualitatively there is an element of adoption that is driven by visual feedback. We sought to capture operator preferences of vibration device design elements to further understand why injectors do not use these devices. We conducted a survey of image preferences among nurses and medical assistants employed at 8 dermatological clinics to investigate barriers to VAD use. Images were electronically modified with features distinct from the original device (a VAD commonly used in clinical practice). Participants rated their likelihood and comfort of use of each VAD represented in the images. Two-sample t-tests were used to compare the rating of the unmodified VAD to each modified VAD within participants. A response rate of 100% was achieved with 35 participants (average age, 38.5 years; 6 (17.1%) male, 29 (82.9%) female). Despite 28 (80%) participants knowing that mechanical vibration reduces ISP, only 16 (45.7%) endorsed ever using mechanical vibration as topical anesthetic. Images modified by pattern, color, and sterility covering were rated significantly lower than the original, unmodified VAD image (plain white VAD), confirming that visual feedback does impact adoption. Through independent comment categorization, aesthetics were found to be important to LAIs. Aesthetic preferences opposing functional concerns may factor into the lack of VAD use. Defining these visual preference barriers to adoption may help promote VAD use during dermatologic procedures.

Defining the Typical Course of Persistent Pulmonary Hypertension of the Newborn: When to Think Beyond Reversible Causes.

OBJECTIVES: To describe the typical clinical course of reversible persistent pulmonary hypertension of the newborn (PPHN) from perinatal etiologies and compare that with the clinical course of PPHN due to underlying fetal developmental etiologies. STUDY DESIGN: This was a single-center, retrospective cohort study of liveborn newborns either born or transferred to our facility for higher level of care between 2015 and 2020 with gestational age ≥35 weeks and a clinical diagnosis of PPHN in the electronic health record. Newborns with complex congenital heart disease and congenital diaphragmatic hernia were excluded. Using all data available at time of collection, newborns were stratified into 2 groups by PPHN etiology - perinatal and fetal developmental causes. Primary outcomes were age at initiation, discontinuation, and total duration of extracorporeal life support, mechanical ventilation, supplemental oxygen, inhaled nitric oxide, inotropic support, and prostaglandin E1. Our secondary outcome was age at echocardiographic resolution of pulmonary hypertension. Groups were compared by t-test. Time-to-event Kaplan Meier curves described and compared (log-rank test) discontinuation of each therapy. RESULTS: Sixty-four (72%) newborns had perinatal etiologies whereas 24 (28%) had fetal developmental etiologies. The resolution of perinatal PPHN was more rapid compared with fetal developmental PPHN. By 10 days of age, more neonates were off inotropes (98% vs 29%, P < .01), decannulated from extracorporeal life support (100% vs 0%, P < .01), extubated (75% vs 37%, P < .01), and had echocardiographic resolution of PH (35% vs 7%, P = .02). CONCLUSIONS: An atypical PPHN course, characterized by persistent targeted therapies in the second week of life, warrants further work-up for fetal developmental causes.

Nutritional value and kinetics of in vitro fermentation of spineless cactus of the genus Nopalea in different phenological phases.

The objective was to evaluate the chemical composition and in vitro fermentation of spineless cactus of the genus Nopalea, F-21 (Nopalea cochenillifera Dyck), IPA-Sertânia (Nopalea cochenillifera Dyck) and Miúda (Nopalea cochenillifera Salm Dyck), in different phenophases. There was no effect (P < 0.05) of the phenological phases of spineless cactus on DM, ash, OM, EE, and CP. Varieties F-21 and Miúda presented higher values of DM and OM, whereas the CP was higher for IPA-Sertânia. The contents of NDF, ADF, and ADL, as well as the fractions of carbohydrates B2 and C were higher in the mature stage, irrespective of the variety. The Miúda variety showed higher levels of NFC and fractions A + B1 and the lower levels of pectin compared to the F-21 and IPA-Sertânia varieties, but not differ of TC to F-21. The volume of gas produced via the degradation of NFC was higher for young phenological phases. The young and intermediate stages showed a higher in vitro digestibility of DM. Based on the results, varieties IPA-Sertânia and Miúda have a high potential for use in animal feed because of their high nutritional quality. Mature cladodes showed a higher fibrous fraction and lower digestibility in all varieties.

TSC2 loss in neural progenitor cells suppresses translation of ASD/NDD-associated transcripts in an mTORC1- and MNK1/2-reversible fashion.

Tuberous sclerosis complex (TSC), an inherited neurodevelopmental (ND) disorder with frequent manifestations of epilepsy and autism spectrum disorder (ASD). TSC is caused by mutations in TSC1 or TSC2 tumor suppressor genes, with encoded proteins hamartin/TSC1 and tuberin/TSC2 forming a functional complex inhibiting mechanistic target of rapamycin complex-1 (mTORC1) signaling, leading to FDA-approved allosteric mTORC1-selective rapamycin analogs for TSC tumors. Rapalogs are effective for TSC-associated hamartomas, however, they are not effective for treating ND manifestations. mTORC1 signaling plays an essential role in protein synthesis through mTORC1-eIF4F and MNK-eIF4E-mediated mRNA translation. Further, the effects on mRNA translation by specific mTORC1 and MNK inhibitors such as RMC-6272 and eFT-508 in TSC have never been explored. Here, employing CRISPR-modified, isogenic TSC2 patient-derived neural progenitor cells (NPCs), we have examined mRNA translation upon loss of TSC2 . Our results reveal dysregulated translation in TSC2 -Null NPCs, which significantly overlap with the translatome from TSC1 -Null NPCs, which we reported recently. Most notably, numerous non-monogenic ASD-NDD- and epilepsy-associated genes identified in patients harboring putative loss-of-function mutations, including protein truncating, or damaging missense variants, were translationally suppressed in TSC2 -Null NPCs, and their translation were reversed upon RMC-6272 or eFT-508 treatment. Our study here establishes the importance of mTORC1-eIF4F and MNK-eIF4E-mediated mRNA translation in TSC, ASD and other neurodevelopmental disorders and lay the groundwork for evaluating drugs in clinical development that target these pathways as a treatment strategy for TSC as well as ASD/NDD.

Pulmonary hypertension in the intensive care unit after pediatric allogeneic hematopoietic stem cell transplant: incidence, risk factors, and outcomes.

Objective: To determine the incidence, risk factors, and outcomes of pulmonary hypertension (PH) in the pediatric intensive care unit (PICU) after pediatric hematopoietic stem cell transplant (HCT). Methods: This was a retrospective study of pediatric patients who underwent allogeneic HCT between January 2008-December 2014 at a center contributing to the Center for International Blood and Marrow Transplant Research data registry. Incidence of PH was assessed from PICU diagnostic codes from records merged from the Virtual Pediatric Systems database. Regression and survival analyses identified factors associated with post-HCT PH. Additional post-HCT morbidities and survival after PH were also assessed. Results: Among 6,995 HCT recipients, there were 29 cases of PH, a cumulative incidence of 0.42% (95% CI 0.27%-0.57%) at 60 months post-HCT. In the sub-cohort of 1,067 patients requiring intensive care after HCT, this accounted for a PH prevalence of 2.72% (95% CI 1.74-3.69%). There was an increased risk of developing PH associated with Black/African American race, metabolic disorders, partially HLA-matched or cord blood allografts, graft-versus-host prophylaxis regimen, and lower pre-HCT functional status. Patients who developed PH had significant PICU comorbidities including heart failure, pulmonary hemorrhage, respiratory failure, renal failure, and infections. Survival at 6 months after diagnosis of post-HCT PH was 51.7% (95% CI 32.5%-67.9%). Conclusions: PH is a rare but serious complication in the pediatric post-HCT population. A significant burden of additional comorbidities, procedural interventions, and risk of mortality is associated with its development. Close monitoring and prompt intervention for this severe complication are necessary in this vulnerable population.

Management of pulmonary vascular disease associated with congenital left-to-right shunts: A single-center experience.

OBJECTIVE: The study objective was to describe the course and outcomes of children under 18 years of age, with left-to-right shunts and pulmonary arterial hypertension undergoing 1 of 2 management approaches: pulmonary arterial hypertension treatment before left-to-right shunt repair (Treat First) and left-to-right shunt repair first with or without subsequent pulmonary arterial hypertension treatment (Repair First). METHODS: We performed a retrospective single-center study, conducted from September 2015 to September 2021, of children with left-to-right shunts and pulmonary arterial hypertension (defined as indexed pulmonary vascular resistance ≥ 4 Wood units [WU]∗m2) but without Eisenmenger physiology. Patient characteristics, longitudinal hemodynamics data, pulmonary arterial hypertension management, left-to-right shunt repair, and outcomes were reviewed. RESULTS: Of 768 patients evaluated for left-to-right shunt closure, 51 (6.8%) had left-to-right shunts associated with pulmonary arterial hypertension (median age 1.1 [0.37-5] years, median indexed pulmonary vascular resistance 6 [5.2-8.7] WU∗m2). In the "Treat First" group (n = 33, 65%), 27 patients (82%) underwent left-to-right shunt closure and 6 patients (18%) did not respond to pulmonary arterial hypertension therapy and did not undergo left-to-right shunt closure. In the "Repair First" group (n = 18, 35%), 12 patients (67%) received pulmonary arterial hypertension therapy and 6 patients (33%) did not. Mortality rates were 6% in the "Treat First" group and 11% in "Repair First" group with follow-ups of 3.4 and 2.5 years, respectively. After left-to-right shunt closure, there was no significant change in indexed pulmonary vascular resistance over a median follow-up of 2 years after surgery (P = .77). CONCLUSIONS: In children with left-to-right shunts and associated pulmonary arterial hypertension, treatment with pulmonary arterial hypertension-targeted therapy before defect repair does not appear to endanger the subjects and may have some benefit. The response to pulmonary arterial hypertension-targeted therapy before shunt closure persists 2 to 3 years postclosure, providing valuable insights into the long-term management of these patients.

Erratum: Gene replacement therapy in a schwannoma mouse model of neurofibromatosis type 2.

[This corrects the article DOI: 10.1016/j.omtm.2022.06.012.].

Feelings as a currency of care: A role for agreeableness in emotional reactivity.

OBJECTIVE AND BACKGROUND: The personality trait of agreeableness is linked to a number of core tendencies (e.g., empathy, warmth) that operate in a feeling-based manner. Following considerations of this type, it is proposed that the motivations and characteristics of agreeable individuals, relative to disagreeable individuals, should render them more receptive to emotional events and more responsive to them for this reason. METHOD: Potential links between agreeableness and emotional reactivity were assessed in two studies involving four samples (total N = 517) in which participants continuously rated their feeling states in response to a variety of affective images. RESULTS: Agreeableness did not predict the speed with which emotional reactions began, but agreeable individuals exhibited higher-magnitude peak intensities, regardless of whether stimuli were appetitive (pleasant) or aversive (unpleasant) in nature. CONCLUSIONS: The findings provide novel insights into the personality trait of agreeableness, emotional reactivity phenomena, and the dynamic processes that link agreeableness to emotion.

Comparative Management Methods for Adolescents With Polycystic Ovarian Syndrome: A Systemic Review.

Polycystic ovarian syndrome (PCOS) is a common endocrinological disorder affecting many adolescents and women of reproductive age worldwide. A diagnosis of PCOS in adolescence relies upon investigating each medical history independently and noting commonly associated symptoms, including obesity, insulin resistance, acne, menstrual abnormalities, and hirsutism. Many researchers are aiming to discover a methodology to help manage the symptoms associated with PCOS, especially in adolescents. This review will investigate management methods possible for adolescents with PCOS. Although the most preferred way to help reduce symptoms is through lifestyle modifications such as vigorous exercise and dietary regimens low in carbohydrates, pharmaceuticals are also offering promising results to adolescents with PCOS. Metformin, oral contraceptives, gonadotropin-releasing hormone (GnRH) antagonists, and other alternatives, including finasteride, eflornithine, fibroblast growth factors (FGFs), and vitamin D, are all shown to help improve insulin sensitivity and regulate menstrual cycles and reduce hirsutism. Epilatory and surgical measurements are also available; however, they are reserved for when all other methods fail and once adulthood or an appropriate age is reached. Although there are many pharmaceuticals available, it is necessary to evaluate each adolescent with PCOS uniquely and prescribe the appropriate pharmacotherapy regarding their symptoms.

Threat sensitivity in emotion dynamics: Negativity effects and sex differences.

Evolutionary theorizing has given rise to the idea that responding to any particular threat may be more mandatory than responding to any particular reward. The present three experiments (total N = 375) sought to provide support for this perspective in an emotion dynamics task in which participants continuously rated their affective state in response to appetitive (reward-related) versus aversive (threat-related) images. Even when equating images for arousal and extremity, several negativity effects (e.g., steeper reactivity slopes in response to aversive images) were found. These negativity effects can serve as an experimental model of threat sensitivity, which should predispose some individuals, more than others, to symptoms related to fear and anxiety. This point was made with respect to sex differences, given that women (relative to men) are diagnosed with anxiety disorders at higher rates. Sex differences were pronounced and extensions of this work, both basic and applied, are proposed.

Congenital infectious encephalopathies from the intrapartum period to postnatal life.

Congenital infections are a common but often underrecognized cause of fetal brain abnormalities, as well as fetal-neonatal morbidity and mortality, that should be considered by all healthcare professionals providing neurological care to fetuses and newborns. Maternal infection with various pathogens (cytomegalovirus, Toxoplasmosis, Rubella virus, Parvovirus B19, lymphocytic choriomeningitis virus, syphilis, Zika virus, varicella zoster virus) during pregnancy can be transmitted to the developing fetus, which can cause multisystem dysfunction and destructive or malformative central nervous system lesions. These can be recognized on fetal and neonatal imaging, including ultrasound and MRI. Imaging and clinical features often overlap, but some distinguishing features can help identify specific pathogens and guide subsequent testing strategies. Some pathogens can be specifically treated, and others can be managed with targeted interventions or symptomatic therapy based on expected complications. Neurological and neurodevelopmental complications related to congenital infections vary widely and are likely driven by a combination of pathophysiologic factors, alone or in combination. These include direct invasion of the fetal central nervous system by pathogens, inflammation of the maternal-placental-fetal triad in response to infection, and long-term effects of immunogenic and epigenetic changes in the fetus in response to maternal-fetal infection. Congenital infections and their neurodevelopmental impacts should be seen as an issue of public health policy, given that infection and the associated complications disproportionately affect woman and children from low- and middle-income countries and those with lower socio-economic status in high-income countries. Congenital infections may be preventable and treatable, which can improve long-term neurodevelopmental outcomes in children.

Vulnerability to APOBEC3G linked to the pathogenicity of deltaretroviruses.

Human retroviruses are derived from simian ones through cross-species transmission. These retroviruses are associated with little pathogenicity in their natural hosts, but in humans, HIV causes AIDS, and human T-cell leukemia virus type 1 (HTLV-1) induces adult T-cell leukemia-lymphoma (ATL). We analyzed the proviral sequences of HTLV-1, HTLV-2, and simian T-cell leukemia virus type 1 (STLV-1) from Japanese macaques (Macaca fuscata) and found that APOBEC3G (A3G) frequently generates G-to-A mutations in the HTLV-1 provirus, whereas such mutations are rare in the HTLV-2 and STLV-1 proviruses. Therefore, we investigated the mechanism of how HTLV-2 is resistant to human A3G (hA3G). HTLV-1, HTLV-2, and STLV-1 encode the so-called antisense proteins, HTLV-1 bZIP factor (HBZ), Antisense protein of HTLV-2 (APH-2), and STLV-1 bZIP factor (SBZ), respectively. APH-2 efficiently inhibits the deaminase activity of both hA3G and simian A3G (sA3G). HBZ and SBZ strongly suppress sA3G activity but only weakly inhibit hA3G, suggesting that HTLV-1 is incompletely adapted to humans. Unexpectedly, hA3G augments the activation of the transforming growth factor (TGF)-ß/Smad pathway by HBZ, and this activation is associated with ATL cell proliferation by up-regulating BATF3/IRF4 and MYC. In contrast, the combination of APH-2 and hA3G, or the combination of SBZ and sA3G, does not enhance the TGF-ß/Smad pathway. Thus, HTLV-1 is vulnerable to hA3G but utilizes it to promote the proliferation of infected cells via the activation of the TGF-ß/Smad pathway. Antisense factors in each virus, differently adapted to control host cellular functions through A3G, seem to dictate the pathogenesis.

Plasma Cell-free RNA Signatures of Inflammatory Syndromes in Children.

Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), Multisystem Inflammatory Syndrome in Children (MIS-C), viral infections and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C - two conditions presenting with overlapping symptoms - with high performance (Test Area Under the Curve (AUC) = 0.97). We further extended this methodology into a multiclass machine learning framework that achieved 81% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes.

Investigating patient engagement associations between a postdischarge texting programme and patient experience, readmission and revisit rates outcomes.

OBJECTIVES: This study aimed (1) to examine the association between patient engagement with a bidirectional, semiautomated postdischarge texting programme and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey outcomes, readmissions and revisit rates in a large health system and (2) to describe operational and clinical flow considerations for implementing a postdischarge texting programme. SETTING: The study involved 1 main academic hospital (beds: 2500+) and 6 community hospitals (beds: 190-400, averaging 300 beds per hospital) in Houston, Texas. METHODS: Retrospective, observational cohort study between non-engaged patients (responded with 0-2 incoming text messages) and engaged patients (responded with 3+ incoming, patient-initiated text messages) between December 2022 and May 2023. We used the two-tailed t-test for continuous variables and χ2 test for categorical variables to compare the baseline characteristics between the two cohorts. For the binary outcomes, such as the revisit (1=yes, vs 0=no) and readmissions (1=yes vs 0=no), we constructed mixed effect logistic regression models with the random effects to account for repeated measurements from the hospitals. For the continuous outcome, such as the case mix index (CMI), a generalised linear quantile mixed effect model was built. All tests for significance were two tailed, using an alpha level of 0.05, and 95% CIs were provided. Significance tests were performed to evaluate the CMI and readmissions and revisit rates. RESULTS: From 78 883 patients who were contacted over the course of this pilot implementation, 49 222 (62.4%) responded, with 39 442 (50%) responded with 3+ incoming text messages. The engaged cohort had higher HCAHPS scores in all domains compared with the non-engaged cohort. The engaged cohort used significantly fewer 30-day acute care resources, experiencing 29% fewer overall readmissions and 20% fewer revisit rates (23% less likely to revisit) and were 27% less likely to be readmitted. The results were statistically significant for all but two hospitals. CONCLUSIONS: This study builds on the few postdischarge texting studies, and also builds on the patient engagement literature, finding that patient engagement with postdischarge texting can be associated with fewer acute care resources. To our knowledge, this is the only study that documented an association between a text-based postdischarge programme and HCAHPS scores, perhaps owing to the bidirectionality and ease with which patients could interact with nurses. Future research should explore the texting paradigms to evaluate their associated outcomes in a variety of postdischarge applications.

Preclinical evaluation of the third-generation, bi-steric mechanistic target of rapamycin complex 1-selective inhibitor RMC-6272 in NF2-deficient models.

Background: NF2-associated meningiomas are progressive, highly morbid, and nonresponsive to chemotherapies, highlighting the need for improved treatments. We have established aberrant activation of the mechanistic target of rapamycin (mTOR) signaling in NF2-deficient tumors, leading to clinical trials with first- and second-generation mTOR inhibitors. However, results have been mixed, showing stabilized tumor growth without shrinkage offset by adverse side effects. To address these limitations, here we explored the potential of third-generation, bi-steric mTOR complex 1 (mTORC1) inhibitors using the preclinical tool compound RMC-6272. Methods: Employing human NF2-deficient meningioma lines, we compared mTOR inhibitors rapamycin (first-generation), INK128 (second-generation), and RMC-6272 (third-generation) using in vitro dose-response testing, cell-cycle analysis, and immunoblotting. Furthermore, the efficacy of RMC-6272 was assessed in NF2-null 3D-spheroid meningioma models, and its in vivo potential was evaluated in 2 orthotopic meningioma mouse models. Results: Treatment of meningioma cells revealed that, unlike rapamycin, RMC-6272 demonstrated superior growth inhibitory effects, cell-cycle arrest, and complete inhibition of phosphorylated 4E-BP1 (mTORC1 readout). Moreover, RMC-6272 had a longer retention time than INK128 and inhibited the expression of several eIF4E-sensitive targets on the protein level. RMC-6272 treatment of NF2 spheroids showed significant shrinkage in size as well as reduced proliferation. Furthermore, in vivo studies in mice revealed effective blockage of meningioma growth by RMC-6272, compared with vehicle controls. Conclusions: Our study in preclinical models of NF2 supports possible future clinical evaluation of third-generation, investigational mTORC1 inhibitors, such as RMC-5552, as a potential treatment strategy for NF2.