Genetic compensation between ribosomal protein paralogs mediated by a cognate circular RNA.

Inter-regulation between related genes, such as ribosomal protein (RP) paralogs, has been observed to be important for genetic compensation and paralog-specific functions. However, how paralogs communicate to modulate their expression levels is unknown. Here, we report a circular RNA involved in the inter-regulation between RP paralogs RpL22 and RpL22-like during Drosophila spermatogenesis. Both paralogs are mutually regulated by the circular stable intronic sequence RNA (sisRNA) circRpL22(NE,3S) produced from the RpL22 locus. RpL22 represses itself and RpL22-like. Interestingly, circRpL22 binds to RpL22 to repress RpL22-like, but not RpL22, suggesting that circRpL22 modulates RpL22's function. circRpL22 is in turn controlled by RpL22-like, which regulates RpL22 binding to circRpL22 to indirectly modulate RpL22. This circRpL22-centric inter-regulatory circuit enables the loss of RpL22-like to be genetically compensated by RpL22 upregulation to ensure robust male germline development. Thus, our study identifies sisRNA as a possible mechanism of genetic crosstalk between paralogous genes.

Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells.

Chemical modulation of proteins enables a mechanistic understanding of biology and represents the foundation of most therapeutics. However, despite decades of research, 80% of the human proteome lacks functional ligands. Chemical proteomics has advanced fragment-based ligand discovery toward cellular systems, but throughput limitations have stymied the scalable identification of fragment-protein interactions. We report proteome-wide maps of protein-binding propensity for 407 structurally diverse small-molecule fragments. We verified that identified interactions can be advanced to active chemical probes of E3 ubiquitin ligases, transporters, and kinases. Integrating machine learning binary classifiers further enabled interpretable predictions of fragment behavior in cells. The resulting resource of fragment-protein interactions and predictive models will help to elucidate principles of molecular recognition and expedite ligand discovery efforts for hitherto undrugged proteins.

Disparities in Screening for Adverse Childhood Experiences.

INTRODUCTION: Screening for adverse childhood experiences (ACEs) in the clinical setting is set to become more commonplace with continued efforts to reimburse clinicians for screening. However, an examination of disparities in ACEs screening and related attitudes and beliefs is needed. METHODS: Using the 2021 California Health Interview Survey (CHIS), this study examined if several measures of socioeconomic status, access to care and identities were associated with 3 outcomes: 1) getting screened for ACEs by a clinician; 2) beliefs about the importance of screening and 3) satisfaction with efforts to address the impacts of ACEs. Logistic regressions were used to estimate odds of the outcomes. RESULTS: Black, Latinx, and Asian individuals had lower odds of being screened for ACEs than non-Hispanic Whites. A recent doctor's visit, higher burden of ACEs, and serious psychological distress were associated with higher odds of being screened. Latinx individuals, women, bisexual individuals, those with a recent doctor's visit and those with serious psychological distress had higher odds of believing clinicians asking about ACEs was very important, relative to their counterparts. Latinx individuals, American Indian or Alaska native individuals, Asian individuals, those with higher educational attainment and those with serious psychological distress had lower odds of being very satisfied with providers' efforts to address the impact of ACEs, relative to their counterparts. CONCLUSIONS: Efforts to expand ACEs screening should consider the disparities in screening that currently exist. Given the wide-ranging impacts that ACEs have on health, an equitable approach to screening is necessary.

Lack of Reliable Transportation for Daily Living Among Adults: United States, 2022.

Access to transportation may be required for many daily tasks, including going to work, health care visits, and obtaining groceries. Previous research suggests that a lack of transportation, especially among adults who are older, uninsured, and have lower incomes, leads to reduced access to health care, which may then lead to adverse health outcomes (1,2). Using data from the 2022 National Health Interview Survey, this report describes the percentage of adults who lacked reliable transportation for daily living in the past 12 months by selected sociodemographic and geographic characteristics.

Discovery of Molecular Glue Degraders via Isogenic Morphological Profiling.

Molecular glue degraders (MGDs) are small molecules that degrade proteins of interest via the ubiquitin-proteasome system. While MGDs were historically discovered serendipitously, approaches for MGD discovery now include cell-viability-based drug screens or data mining of public transcriptomics and drug response datasets. These approaches, however, have target spaces restricted to the essential proteins. Here we develop a high-throughput workflow for MGD discovery that also reaches the nonessential proteome. This workflow begins with the rapid synthesis of a compound library by sulfur(VI) fluoride exchange chemistry coupled to a morphological profiling assay in isogenic cell lines that vary in levels of the E3 ligase CRBN. By comparing the morphological changes induced by compound treatment across the isogenic cell lines, we were able to identify FL2-14 as a CRBN-dependent MGD targeting the nonessential protein GSPT2. We envision that this workflow would contribute to the discovery and characterization of MGDs that target a wider range of proteins.

Demographic Differences in Life Dissatisfaction Among Adults: United States, 2021.

Objective-Previous work has established life satisfaction as an important indicator of overall health and well-being. This report describes differences in life dissatisfaction by selected characteristics, grouped by family income. Methods-Data from the 2021 National Health Interview Survey were used to examine the percentage of adults that were dissatisfied with life by selected demographic characteristics (age, sex, race and Hispanic origin, and nativity status [born in the United States or U.S. territory]), grouped by family income. Results-In 2021, 4.8% of adults were dissatisfied with life. In general, analyses showed significant differences by all selected demographic characteristics among adults with incomes of less than 200% of the federal poverty level. Among this group, men, adults ages 45-64, White non-Hispanic adults, Black non-Hispanic adults, and adults born in the United States were more likely to be dissatisfied with life compared with their counterparts. No significant differences in life dissatisfaction by selected demographic characteristics among adults with incomes greater than 200% of the federal poverty level were observed. Conclusion-This report presents estimates of life dissatisfaction among adults by demographic subgroups and family income. These results highlight the importance of monitoring life dissatisfaction among detailed subgroups grouped by income, in addition to the overall national estimate.

Stressful Life Events and Healthcare Utilization Among U.S. Children Aged 2-17 Years.

Objective-Associations between stressful life events (SLEs) during childhood and suboptimal healthcare access and use has been documented. Recent changes to the National Health Interview Survey's questionnaire enabled the inclusion of SLEs in the child sample, resulting in an additional national data source where SLEs can be tracked. In this report, the latest SLE estimates are examined for children aged 2-17 years in the United States and their associations with healthcare utilization. Methods-Data from the 2021 National Health Interview Survey were used to examine the percentage of children who experienced one or more SLEs-emotional abuse, unmet basic needs, experiences of racism, household mental illness, household substance abuse, parental incarceration, and exposure to neighborhood violence-and describe the association between SLEs and selected healthcare utilization indicators over the past 12 months (as in no well-child visit, emergency room visits, urgent care visits, unmet medical care needs due to cost, use of prescription medications for mental health, and use of any mental health therapy). Multivariate logistic regression models were fit to produce prevalence ratios for selected healthcare utilization indicators by SLEs, after adjusting for child and family sociodemographic characteristics. Results-In 2021, one in five children aged 2-17 years had ever experienced an SLE. In general, all SLEs were related to higher healthcare utilization (as in emergency department visits or mental health therapy) and unmet medical care needs. In general, no significant associations were found between experiencing SLEs and not receiving preventive health care. After adjusting for demographic characteristics, higher rates of healthcare utilization, unmet medical care needs, and mental healthcare utilization generally persisted for children with SLEs. Conclusion-This report expands knowledge on the relationship between childhood SLEs and the use of preventive care, healthcare utilization, and mental health care. National Health Interview Survey data can be used to monitor trends in these associations over time.

A window of opportunity: Adverse childhood experiences and time alone with a provider in the United States.

BACKGROUND: To date, there is limited literature on the relationship between Adverse Childhood Experiences (ACEs) and the quality of health care provider encounters. This is key, as people with a history of ACEs have a greater burden of illness. METHODS: This study uses data from the 2020-2021 National Survey of Children's Health to examine relationships between ACEs and (1) spending less than ten minutes with a health care provider, and (2) spending time alone with a health care provider. RESULTS: In general, our results suggested most ACEs were associated with higher odds of a provider spending <10 min with a child during their last preventative care visit, while ACEs were inconsistently related to spending time alone with a provider. Each additional ACE was found to be associated with higher odds of both outcomes. CONCLUSIONS: This work emphasizes the importance of ACEs screening in a health care setting and may set the groundwork for future research investigating mechanisms within these associations. Given the established link between health care quality and patient-provider trust, and health outcomes, intervention work is needed to develop healthcare practices that may encourage the length and quality of health care provider visits.

Diagnosed Developmental Disabilities in Children Aged 3-17 Years: United States, 2019-2021.

Developmental disabilities are common in children in the United States, and the prevalence has increased in recent years (1). Timely estimates are necessary to assess the adequacy of services and interventions that children with developmental disabilities typically need (2). This report provides updated prevalence estimates for diagnosed autism spectrum disorder, intellectual disability, and other developmental delay among children aged 3-17 years from the 2019-2021 National Health Interview Survey (NHIS), with differences in prevalence examined between years and by sex, age group, and race and Hispanic origin. Estimates are also presented for any developmental disability, defined as having had one or more of these three diagnoses.

Mental Health Treatment Among Children Aged 5-17 Years: United States, 2021.

Mental health disorders, such as attention-deficit/hyperactivity disorder, anxiety, and behavioral conditions, are common in school-aged children in the United States (1). Frontline treatments for mental health disorders can include medication, counseling or therapy, or both, depending on the condition and the age of the child (2). This report describes the percentage of children aged 5-17 years who have received mental health treatment in the past 12 months by selected characteristics, based on data from the 2021 National Health Interview Survey. Mental health treatment is defined as having taken medication for mental health, received counseling or therapy from a mental health professional, or both in the past 12 months.

The perceived neighborhood walking environment and self-reported sleep health in a nationally representative sample of the United States.

Neighborhood environment can influence sleep health; yet, there is a lack of data on specific environment features in nationally representative samples. We used the 2020 National Health Interview Survey to determine associations between perceived built and social environment factors related to pedestrian access (walking paths, sidewalks), amenities (shops, transit stops, entertainment/services, places to relax), and unsafe walking conditions (traffic, crime) and self-reported sleep duration and disturbances. Places to relax and pedestrian access were associated with better sleep health while unsafe walking conditions were associated with worse sleep health. Access to amenities (shops, transit stops, entertainment venues) had null associations with sleep health.

Adverse Childhood Experiences and Family-Centered Care.

Adverse Childhood Experiences (ACEs) include experiences of child maltreatment and household dysfunction. Prior work has shown that children with ACEs may have suboptimal utilization of preventive health care, including annual well-visits, however little is known about the relationship between ACEs and quality of patient care. Using data from the 2020 National Survey of Children's Health (N = 22,760) a series of logistic regression models estimated associations between ACEs, both individually and cumulatively, and five components of family-centered care. Most ACEs were consistently associated with lower odds of family-centered care (e.g. financial hardship was associated with doctors always spend enough time with children, AOR = 0.53; 95% CI = 0.47, 0.61), except for having a parent or guardian die, which was associated with higher odds. Cumulative ACE score was also associated with lower odds of family-centered care (e.g. doctors always listened carefully to the parent, AOR = 0.86; 95% CI = 0.81, 0.90). These findings emphasize the importance of the consideration of ACEs in the context of family-centered care, and support the need for ACEs screening in the clinical setting. Future work should focus on mechanisms explaining the observed associations.

Health Conditions and Health Care Use Among American Indian and Alaska Native Adults by Tribal Land Residential Status: United States, 2019-2021.

Objective-This report presents estimates for selected health conditions and health care use among American Indian and Alaska Native (AIAN) adults by tribal land residential status.

Telemedical Support Using Smartphones for Spine Surgery in Low- and Middle-Income Countries.

Objective: Low- and middle-income countries (LMICs) face many challenges compared to industrialized nations, most notably in regard to the health care system. Patients often have to travel long distances to receive medical care with few reliable transportation mechanisms. In time-critical emergencies, this is a significant disadvantage. One specialty that is particularly affected by this is spine surgery. Within this field, traumatic injuries and acutely compressive pathologies are often time-critical. Increasing global networking capabilities through internet access offers the possibility for telemedical support in remote regions. Recently, high-performance cameras and processors became available in commercially available smartphones. Due to their wide availability and ease of use, this could provide a unique opportunity to offer telemedical support in LMICs. Methods: We conducted a feasibility study with a neurosurgical institution in east Africa. To ensure telemedical support, a commercially available smartphone was selected as the experimental hardware. Preoperatively, resolution, contrast, brightness, and color reproduction were assessed under theoretical conditions using a test chart. Intraoperatively, the image quality was assessed under different conditions. In the first step, the instrumentation table was displayed, and the mentor surgeon marked an instrument that the mentee surgeon should recognize correctly. In the next evaluation step, the surgical field was shown on film and the mentor surgeon marked an anatomical structure, and in the last evaluation step, the screen of the X-ray machine was captured, and the mentor surgeon again marked an anatomical structure. Subjective image quality was rated by two independent reviewers using the similar modified Likert scale as before on a scale of 1-5, with 1 indicating inadequate quality and 5 indicating excellent quality. Results: The image quality during the video calls was rated as sufficient overall. When evaluating the test charts, a quality of 97% ± 5 on average was found for the chart with the white background and a quality of 84% ± 5 on average for the chart with the black background. The color reproduction, the contrast, and the reproduction of brightness were rated excellent. Intraoperatively, the visualization of the instrument table was also rated excellent. Visualization of the operative site was rated 1.5 ± 0.5 on average and it was not possible to recognize relevant anatomical structures with the required confidence for surgical procedures. Image quality of the X-ray screen was rated 1.5 ± 0.9 on average. Conclusion: Current generation smartphones have high imaging performance, high computing power, and excellent connectivity. However, relevant anatomical structures during spine surgery procedures and on the X-ray screen in the operating room could not be identified with reliability to provide adequate surgical support. Nevertheless, our study showed the potential in smartphones supporting surgical procedures in LMICs, which could be helpful in other surgical fields.

Decompression alone versus decompression with fusion in patients with lumbar spinal stenosis with degenerative spondylolisthesis: a systematic review and meta-analysis.

INTRODUCTION: Surgical decompression is standard care in the treatment of degenerative spondylolisthesis in patients with symptomatic lumbar spinal stenosis, but there remains controversy over the benefits of adding fusion. The persistent lack of consensus on this matter and the availability of new data warrants a contemporary systematic review and meta-analysis of the literature. METHODS: Multiple online databases were systematically searched up to October 2022 for randomized controlled trials (RCTs) and prospective studies comparing outcomes of decompression alone versus decompression with fusion for lumbar spinal stenosis in patients with degenerative spondylolisthesis. Primary outcome was the Oswestry Disability Index. Secondary outcomes included leg and back pain, surgical outcomes, and radiological outcomes. Pooled effect estimates were calculated and presented as mean differences (MD) with their 95% confidence intervals (CI) at two-year follow-up. RESULTS: Of the identified 2403 studies, eventually five RCTs and two prospective studies were included. Overall, most studies had a low or unclear risk of selection bias and most studies were focused on low grade degenerative spondylolisthesis. All patient-reported outcomes showed low statistical heterogeneity. Overall, there was high-quality evidence suggesting no difference in functionality at two years of follow-up (MD - 0.31, 95% CI - 3.81 to 3.19). Furthermore, there was high-quality evidence of no difference in leg pain (MD - 1.79, 95% CI - 5.08 to 1.50) or back pain (MD - 2.54, 95% CI - 6.76 to 1.67) between patients undergoing decompression vs. decompression with fusion. Pooled surgical outcomes showed less blood loss after decompression only, shorter length of hospital stay, and a similar reoperation rate compared to decompression with fusion. CONCLUSION: Based on the current literature, there is high-quality evidence of no difference in functionality after decompression alone compared to decompression with fusion in patients with degenerative lumbar spondylolisthesis at 2 years of follow-up. Further studies should focus on long-term comparative outcomes, health economic evaluations, and identifying those patients that may benefit more from decompression with fusion instead of decompression alone. This review was registered at Prospero (CRD42021291603).

Diagnosed Allergic Conditions in Adults: United States, 2021.

An allergy occurs when an individual's immune system misclassifies typically harmless substances as harmful and has a specific and reproducible immune response (1,2). The severity of allergy symptoms can range from itchy, watery eyes and hives to life-threatening anaphylaxis, and the presence of allergies can negatively impact an individual's quality of life (3-6). This report uses 2021 National Health Interview Survey (NHIS) data to describe the prevalence of seasonal allergies, eczema, and food allergies in adults in the United States.

Retrospective reports of socioeconomic disadvantage in childhood and mortality risk: are associations consistent across measures and sex?

Although prior research has established associations between childhood socioeconomic disadvantage and all-cause mortality, there is still limited research investigating (1) the consistency between subjective and objective reports of childhood socioeconomic status, (2) sex differences in the associations between childhood socioeconomic disadvantage and all-cause mortality, and (3) potential mediators within these associations. Drawing on data from the Midlife in the United States (MIDUS) cohort (N = 7425), we examined the associations between three distinct indicators of childhood socioeconomic disadvantage and all-cause mortality risk, and whether these associations differ for males and females. Among males only, lower perceived relative childhood financial status, lower levels of parents' education, and receipt of welfare during childhood were associated with excess mortality risk, adjusted for age and minority status, with adjusted hazard ratios ranging from 1.24 (95% confidence interval (CI): 1.02, 1.51) for perceived childhood financial status to 1.28 (95% CI: 1.11, 1.47) for welfare in childhood. When additionally adjusted for education, substance use, depression, and underlying health conditions, only childhood welfare status maintained an association with mortality (AHR, 1.17; 95% CI, 1.02-1.35). Mediation analyses among males revealed that education, substance use, depression, and underlying health conditions accounted for substantial proportions of these associations, ranging from 31.03 to 57.63%, across indicators of childhood socioeconomic disadvantage. Future research is needed to clarify the developmental mechanisms that lead to sex differences and identify effective strategies to intervene on the relation between childhood socioeconomic position and excess mortality risk among males.

Genome-centric analysis of short and long read metagenomes reveals uncharacterized microbiome diversity in Southeast Asians.

Despite extensive efforts to address it, the vastness of uncharacterized 'dark matter' microbial genetic diversity can impact short-read sequencing based metagenomic studies. Population-specific biases in genomic reference databases can further compound this problem. Leveraging advances in hybrid assembly (using short and long reads) and Hi-C technologies in a cross-sectional survey, we deeply characterized 109 gut microbiomes from three ethnicities in Singapore to comprehensively reconstruct 4497 medium and high-quality metagenome assembled genomes, 1708 of which were missing in short-read only analysis and with >28× N50 improvement. Species-level clustering identified 70 (>10% of total) novel gut species out of 685, improved reference genomes for 363 species (53% of total), and discovered 3413 strains unique to these populations. Among the top 10 most abundant gut bacteria in our study, one of the species and >80% of strains were unrepresented in existing databases. Annotation of biosynthetic gene clusters (BGCs) uncovered more than 27,000 BGCs with a large fraction (36-88%) unrepresented in current databases, and with several unique clusters predicted to produce bacteriocins that could significantly alter microbiome community structure. These results reveal significant uncharacterized gut microbial diversity in Southeast Asian populations and highlight the utility of hybrid metagenomic references for bioprospecting and disease-focused studies.

Ten-Step 3-Dimensional-Navigated Single-Stage Lateral Surgery With Microtubular Decompression: A Case Series.

BACKGROUND: Single-stage lateral lumbar interbody fusion is a safe and effective procedure that relies on indirect decompression and fusion to treat various lumbar pathologies. This technique, however, has an overall 9% rate of indirect decompression failure, which may require additional surgery to achieve adequate direct decompression. To address this concern, we modified this technique by adding a minimally invasive, direct tubular decompression in lateral position when indicated. No study has described the technical nuances of incorporating a microtubular decompression into the single-stage lateral lumbar interbody fusion workflow (SSLLIF+). OBJECTIVE: To report on the procedural steps and clinical outcomes of the SSLLIF+. METHODS: In this retrospective case series of prospectively collected data, we present the detailed surgical approach of the SSLLIF+ with a single-center case series over a 5-year period. Surgical and clinical outcomes are presented. RESULTS: A total of 7 patients underwent a SSLLIF+ with a total of 18 levels fused and 7 levels decompressed. The SSLLIF+ was successfully performed in all cases without the occurrence of intraoperative complications in this case series. There was 1 revision after 20 months of follow-up because of adjacent segment disease. There was no need for further direct decompression in a delayed fashion. CONCLUSION: SSLLIF with direct microtubular decompression in lateral position is a safe and effective procedure in patients where indirect decompression alone may not achieve the surgical goal. Adherence to minimally invasive spine surgery principles and thoughtful patient selection facilitate the successful management of these patients while demonstrating short hospital stay and low-risk of perioperative complications.

Long-term ecological and evolutionary dynamics in the gut microbiomes of carbapenemase-producing Enterobacteriaceae colonized subjects.

Long-term colonization of the gut microbiome by carbapenemase-producing Enterobacteriaceae (CPE) is a growing area of public health concern as it can lead to community transmission and rapid increase in cases of life-threatening CPE infections. Here, leveraging the observation that many subjects are decolonized without interventions within a year, we used longitudinal shotgun metagenomics (up to 12 timepoints) for detailed characterization of ecological and evolutionary dynamics in the gut microbiome of a cohort of CPE-colonized subjects and family members (n = 46; 361 samples). Subjects who underwent decolonization exhibited a distinct ecological shift marked by recovery of microbial diversity, key commensals and anti-inflammatory pathways. In addition, colonization was marked by elevated but unstable Enterobacteriaceae abundances, which exhibited distinct strain-level dynamics for different species (Escherichia coli and Klebsiella pneumoniae). Finally, comparative analysis with whole-genome sequencing data from CPE isolates (n = 159) helped identify substrain variation in key functional genes and the presence of highly similar E. coli and K. pneumoniae strains with variable resistance profiles and plasmid sharing. These results provide an enhanced view into how colonization by multi-drug-resistant bacteria associates with altered gut ecology and can enable transfer of resistance genes, even in the absence of overt infection and antibiotic usage.