Linguistic isolation correlates with length of stay and mortality for pediatric oncology patients in California.

OBJECTIVE: To evaluate social drivers of health and how they impact pediatric oncology patients' clinical outcomes during pediatric intensive care unit (PICU) admission via correlation with patient ZIP codes. METHODS: Demographic, clinical, and outcome variables from Virtual Pediatric Systems®, LLC for oncology patients (2009-2021) in California PICUs (excluding postoperative) using 3-digit ZIP Codes with social drivers of health variables linguistic isolation, poverty, race/ethnicity, and education abstracted from American Community Survey data for 3-digit ZIP Codes using the Environmental Protection Agency's EJScreen tool. Outcomes of length of stay (LOS), mortality, acuity scores, were compared with social variables. RESULTS: Positive correlation between mortality and minority racial groups (Hispanic/Latino) across ZIP Codes (correlation coefficients of 0.45 (95% CI: 0.22-0.64, p < 0.001) in 2017, 0.50 (95% CI: 0.27-0.68, p < 0.001) in 2018, 0.33 (95% CI: 0.07-0.54, p = 0.013) in 2020, and 0.32 (95% CI: 0.06-0.53, p = 0.018) in 2021). Median PICU length of stay significantly correlated with linguistic isolation (coefficient of 0.42 (95% CI: 0.18-0.61, p = 0.001) in 2021 versus -0.41 (95% CI: -0.61 to -0.16, p = 0.002) in 2019), which included PRISMIII (n = 7417). Mixed effects logistic regression model for other constant variables (PRISMIII, cancer type, race/ethnicity, year), random effect of patient, linguistic isolation (percentage as a continuous value) was significantly associated (95% CI: 1.01-1.06; p = 0.02) with mortality; (OR = 1.03). CONCLUSIONS: Linguistic isolation was correlated with LOS and mortality, however variable year to year.

Patient-reported barriers for adherence to prophylactic enoxaparin after orthopedic trauma surgery.

INTRODUCTION: Venous thromboembolism following orthopedic trauma surgery remains prevalent despite prophylaxis being a standard of care. Enoxaparin injection is a commonly utilized prophylaxis regimen among high-risk patients. Patient-reported rates of nonadherence and barriers to enoxaparin use are not described in the literature. A better understanding of these barriers and their impact on adherence to post-discharge prophylaxis regimens may shed light on persistent outcomes gaps. MATERIALS AND METHODS: Semi-structured interviews were administered to adult patients prescribed prophylactic enoxaparin and presenting to orthopedic surgery outpatient clinic at an urban level 1 trauma center for a post-operative appointment following traumatic injury from April to July 2023. Patients self-reported their age, gender, race, and mobility. Inductive thematic analysis with three-reviewer consensus identified common barriers among responses. Adherence rates were calculated by dividing patients' estimated number of missed doses over total prescribed doses at the point of inquiry. RESULTS: We identified 154 eligible patients through chart review, and 50 enrolled and interviewed. Participants had a mean age of 37 years. Of 50 participants, 20 identified as female; 25 identified as Black or African American, 16 as White, 5 as Hispanic, 2 as Asian, and 2 as multiracial. Twenty-one participants were non-ambulatory at time of interview. Mean and median patient-reported adherence were 64.5 % (SD 35.5) and 70.5 % (IQR 33-100) respectively. Five patients reported complete nonadherence, while 17 patients reported perfect adherence. Every participant reporting complete nonadherence identified as Black or African American, as compared to 8 out of 17 reporting perfect adherence. Despite acknowledging a twice-daily prescription, 17 patients reported once-daily rather than twice-daily use. Inductive thematic analysis revealed the following six barriers to prophylaxis adherence (number of participants reporting): Inconvenience (18 patients), Pain (16), Fear (12), Acquisition (7), Bruising (7), and Mechanism (7). Altogether, 40 patients endorsed at least one barrier to adherence. DISCUSSION & CONCLUSIONS: Most patients face barriers to adherence with post-discharge prophylactic enoxaparin, and the resultant rates of adherence are low. This may contribute to persistent outcomes gaps in the orthopedic trauma population despite prophylaxis standards. Changes in prescribing patterns and patient engagement techniques may improve post-operative thromboembolic outcomes.

Can Patient-centered Education and Pain Management Delivered by Coaches Improve Pain Outcomes After Orthopaedic Trauma? A Randomized Trial.

BACKGROUND: Pain after orthopaedic trauma is complex, and many patients who have experienced orthopaedic trauma are at increased risk for prolonged opioid utilization after the injury. Patient-centered interventions capable of delivering enhanced education and opioid-sparing pain management approaches must be implemented and evaluated in trauma care settings to improve pain outcomes and minimize opioid-related risks. QUESTIONS/PURPOSES: Does personalized pain education and management delivered by coaches (1) improve pain-related outcomes, (2) reduce opioid consumption, and (3) improve patient-reported outcome measures (Patient-Reported Outcomes Measurement Information System [PROMIS] scores) compared to written discharge instructions on pain management and opioid safety? METHODS: This clinical trial aimed to examine the effect of a personalized pain education and management intervention, delivered by paraprofessional coaches, on pain-related outcomes and opioid consumption compared with usual care (written discharge instructions on pain management and opioid safety). Between February 2021 and September 2022, 212 patients were randomized to the intervention (49% [104]) or control group (51% [108]). A total of 31% (32 of 104) and 47% (51 of 108) in those groups, respectively, were lost before the minimum study follow-up of 12 weeks or had incomplete datasets, leaving 69% (72 of 104) and 53% (57 of 108) for analysis in the intervention and control group, respectively. Patients randomized to the intervention worked with the paraprofessional coaches throughout hospitalization after their orthopaedic injury and at their 2-, 6-, and 12-week visits with the surgical team after discharge to implement mindfulness-based practices and nonpharmacological interventions. Most participants in the final sample of 129 identified as Black (73% [94 of 129]) and women (56% [72 of 129]), the mean Injury Severity score was 8 ± 4, and one-third of participants were at medium to high risk for an opioid-use disorder based on the Opioid Risk Tool. Participants completed surveys during hospitalization and at the 2-, 6-, and 12-week follow-up visits. Surveys included average pain intensity scores over the past 24 hours measured on the pain numeric rating scale from 0 to 10 and PROMIS measures (physical functioning, pain interference, sleep disturbance). Opioid utilization, measured as daily morphine milligram equivalents, was collected from the electronic health record, and demographic and clinical characteristics were collected from self-report surveys. Groups were compared in terms of mean pain scores at at the 12-week follow-up, daily morphine milligram equivalents both during inpatient and at discharge, and mean PROMIS scores at 12 weeks of follow-up. Additionally, differences in the proportion of participants in each group achieving minimum clinically important differences (MCID) on pain and PROMIS scores were examined. For pain scores, an MCID of 2 points on the pain numeric rating scale assessing past 24-hour pain intensity was utilized. RESULTS: We found no difference between the intervention and control in terms of mean pain score at 12 weeks nor in the proportions of patients who achieved the MCID of 2 points for 24-hour average pain scores (85% [61 of 72] versus 72% [41 of 57], respectively, OR 2.2 [95% confidence interval (CI) 0.9 to 5.3]; p = 0.08). No differences were noted in daily morphine milligram equivalents utilized between the intervention and control groups during hospitalization, at discharge, or in prescription refills. Similarly, we observed no differences in the proportions of patients in the intervention and control groups who achieved the MCID on PROMIS Physical Function (81% [58 of 72] versus 63% [36 of 57], respectively, OR 2.2 [95% CI 0.9 to 5.2]; p = 0.06). We saw no differences in the proportions of patients who achieved the MCID on PROMIS Sleep Disturbance between the intervention and control groups (58% [42 of 72] versus 47% [27 of 57], respectively, OR 1.4 [95% CI 0.7 to 3.0]; p = 0.31). The proportion of patients who achieved the MCID on PROMIS Pain Interference scores did not differ between the intervention and the control groups (39% [28 of 72] versus 37% [21 of 57], respectively, OR 1.1 [95% CI 0.5 to 2.1]; p = 0.95). CONCLUSION: In this trial, we observed no differences between the intervention and control groups in terms of pain outcomes, opioid medication utilization, or patient-reported outcomes after orthopaedic trauma. However, future targeted research with diverse samples of patients at increased risk for poor postoperative outcomes is warranted to ascertain a potentially meaningful patient perceived effect on pain outcomes after working with coaches. Other investigators interested in this interventional approach may consider the coach program as a framework at their institutions to increase access to evidence-based nonpharmacological interventions among patients who are at increased risk for poor postoperative pain outcomes. Smaller, more focused programs connecting patients to coaches to learn about nonpharmacological pain management interventions may deliver a larger impact on patient's recovery and outcomes. LEVEL OF EVIDENCE: Level I, therapeutic study.

Risk of autism spectrum disorder in children with infantile epileptic spasms syndrome: a retrospective study in a single center in Brazil.

OBJECTIVE: This study aimed to investigate the prevalence of autism spectrum disorder and its possible correlations with clinical characteristics in patients with infantile epileptic spasms syndrome in a single center in Brazil. METHODS: This retrospective cross-sectional study examined 53 children with the diagnosis of infantile epileptic spasms syndrome prior to an autism spectrum disorder assessment. Participants were divided into two groups based on the presence or absence of autism spectrum disorder. Available variables (sex, medications, median age at onset of infantile epileptic spasms syndrome, and presence of comorbidities) were compared using Mann-Whitney U or chi-square tests. RESULTS: Among the included patients, 12 (23 %) were diagnosed with autism spectrum disorder, corresponding to a relative risk of 0.29 (95 % confidence interval 0.174-0.492). The age at the first seizure ranged from 3 to 15 months, with a mean of 6.65 months. This age significantly differed between participants with autism spectrum disorder (10.58 months) and those without (5.43 months), p<0.001. CONCLUSION: Children with infantile epileptic spasms syndrome have a higher risk of being diagnosed with autism spectrum disorder. Later age of onset and period of spasm occurrence might be predisposing risk factors.

Corrigendum: Phenotypic and transcriptional characterization of F. tularensis LVS during transition into a viable but non-culturable state.

[This corrects the article DOI: 10.3389/fmicb.2024.1347488.].

Large-scale mutational analysis identifies UNC93B1 variants that drive TLR-mediated autoimmunity in mice and humans.

Nucleic acid-sensing Toll-like receptors (TLR) 3, 7/8, and 9 are key innate immune sensors whose activities must be tightly regulated to prevent systemic autoimmune or autoinflammatory disease or virus-associated immunopathology. Here, we report a systematic scanning-alanine mutagenesis screen of all cytosolic and luminal residues of the TLR chaperone protein UNC93B1, which identified both negative and positive regulatory regions affecting TLR3, TLR7, and TLR9 responses. We subsequently identified two families harboring heterozygous coding mutations in UNC93B1, UNC93B1+/T93I and UNC93B1+/R336C, both in key negative regulatory regions identified in our screen. These patients presented with cutaneous tumid lupus and juvenile idiopathic arthritis plus neuroinflammatory disease, respectively. Disruption of UNC93B1-mediated regulation by these mutations led to enhanced TLR7/8 responses, and both variants resulted in systemic autoimmune or inflammatory disease when introduced into mice via genome editing. Altogether, our results implicate the UNC93B1-TLR7/8 axis in human monogenic autoimmune diseases and provide a functional resource to assess the impact of yet-to-be-reported UNC93B1 mutations.

Effects of superparamagnetic iron oxide nanoparticles (SPIONS) testicular injection on Leydig cell function and sperm production in a murine model.

In the domain of medical advancement, nanotechnology plays a pivotal role, especially in the synthesis of biocompatible materials for therapeutic use. Superparamagnetic Iron Oxide Nanoparticles (SPIONs), known for their magnetic properties and low toxicity, stand at the forefront of this innovation. This study explored the reproductive toxicological effects of Sodium Citrate-functionalized SPIONs (Cit_SPIONs) in adult male mice, an area of research that holds significant potential yet remains largely unknown. Our findings reveal that Cit_SPIONs induce notable morphological changes in interstitial cells and the seminiferous epithelium when introduced via intratesticular injection. This observation is critical in understanding the interactions of nanomaterials within reproductive biological systems. A striking feature of this study is the rapid localization of Cit_SPIONs in Leydig cells post-injection, a factor that appears to be closely linked with the observed decrease in steroidogenic activity and testosterone levels. This data suggests a possible application in developing nanostructured therapies targeting androgen-related processes. Over 56 days, these nanoparticles exhibited remarkable biological distribution in testis parenchyma, infiltrating various cells within the tubular and intertubular compartments. While the duration of spermatogenesis remained unchanged, there were many Tunel-positive germ cells, a notable reduction in daily sperm production, and reduced progressive sperm motility in the treated group. These insights not only shed light on the intricate mechanisms of Cit_SPIONs interaction with the male reproductive system but also highlight the potential of nanotechnology in developing advanced biomedical applications.

Opioid utilization after orthopaedic trauma hospitalization among Medicaid-insured adults.

Opioids are vital to pain management and sedation after trauma-related hospitalization. However, there are many confounding clinical, social, and environmental factors that exacerbate pain, post-injury care needs, and receipt of opioid prescriptions following orthopaedic trauma. This retrospective study sought to characterize differences in opioid prescribing and dosing in a national Medicaid eligible sample from 2010-2018. The study population included adults, discharged after orthopaedic trauma hospitalization, and receiving an opioid prescription within 30 days of discharge. Patients were identified using the International Classification of Diseases (ICD-9; ICD-10) codes for inpatient diagnosis and procedure. Filled opioid prescriptions were identified from National Drug Codes and converted to morphine milligram equivalents (MME). Opioid receipt and dosage (e.g., morphine milligram equivalents [MME]) were examined as the main outcomes using regressions and analyzed by year, sex, race/ethnicity, residence rurality-urbanicity, and geographic region. The study population consisted of 86,091 injured Medicaid-enrolled adults; 35.3% received an opioid prescription within 30 days of discharge. Male patients (OR = 1.12, 95% CI: 1.07-1.18) and those between 31-50 years of age (OR = 1.15, 95% CI: 1.08-1.22) were found to have increased odds ratio of receiving an opioid within 30 days of discharge, compared to female and younger patients, respectively. Patients with disabilities (OR = 0.75, 95% CI: 0.71-0.80), prolonged hospitalizations, and both Black (OR = 0.87, 95% CI: 0.83-0.92) and Hispanic patients (OR = 0.72, 95% CI: 0.66-0.77), relative to white patients, had lower odds ratio of receiving an opioid prescription following trauma. Additionally, Black and Hispanic patients received lower prescription doses compared to white patients. Individuals hospitalized in the Southeastern United States and those between the ages of 51-65 age group were found to be prescribed lower average daily MME. There were significant variations in opioid prescribing practices by race, sex, and region. National guidelines for use of opioids and other pain management interventions in adults after trauma hospitalization may help limit practice variation and reduce implicit bias and potential harms in outpatient opioid usage.

Massed written exposure therapy delivered to veterans with posttraumatic stress symptoms on an acute inpatient mental health unit.

Written exposure therapy (WET) is a brief, manualized trauma-focused treatment typically delivered in five individual weekly sessions. Given the brevity and effectiveness of WET, researchers have begun to focus on its delivery in a massed format. However, only one case study examining massed delivery has been published to date. As such, the objective of the current study was to examine the acceptability, feasibility, and preliminary effectiveness of massed WET among veterans with a trauma- and stressor-related disorder receiving care on an acute inpatient mental health unit. Veterans (N = 26) were assessed prior to, immediately after, and 1 month following massed WET. Most veterans found massed WET to be useful and acceptable. Recruitment and retention rates suggested that the treatment was feasible. Notably, the results revealed statistically significant reductions in overall posttraumatic stress symptoms, ηp 2 = .81, p < .001; depressive symptoms, ηp 2 = .71, p < .001; and functional impairment, ηp 2 = .42, p = .002. These findings add to a growing body of literature highlighting the preliminary effectiveness of WET across various settings, populations, and delivery formats. Limitations include the small sample size and uncontrolled design.

Calculated Medicine: Seven Decades of Accelerating Growth.

The field of Calculated Medicine has grown substantially over the last 7 decades. Comprised of objective, evidence-based medical decision tools, Calculated Medicine has broad application in medical practice, medical research, and health care management. This article reviews the history and varied methodologies of Calculated Medicine, starting with the 1953 Apgar score and concluding with a look into modern computational tools of the field: machine learning, natural language processing, artificial intelligence, and in silico research techniques. We'll also review and quantify the rapidly accelerating growth of Calculated Medicine in the medical literature. Our database of journal articles referring to the field has accumulated over 1.8 million citations, with more than 460 new citations (on average) posted every day. Using natural language processing, we examine and analyze this burgeoning database. Lastly, we examine an important new direction of Calculated Medicine: self-reflection on its potential effect on racial and ethnic disparities in health care. Our field is making great strides promoting health care egality, and some of the most prominent contributions will be reviewed.

Characteristics of Opsoclonus-Myoclonus Syndrome in Patients of the Largest Pediatric Hospital in Latin America.

BACKGROUND: Opsoclonus-myoclonus syndrome (OMS) is a rare neuroinflammatory disorder characterized by ataxia, opsoclonus, and myoclonus. Clinical diagnosis of OMS has been challenging; therefore, we sought to determine the clinical and treatment profiles of patients with OMS at the largest pediatric hospital in Latin America. METHODS: We analyzed the data of patients diagnosed with OMS between 2010 and 2020 at Pequeno Principe Hospital (Brazil) to determine the corresponding clinical profile more accurately. RESULTS: Of the approximately 50,000 visitors to our pediatric neurology department from 2010 to 2020, 10 patients with OMS were observed. Five nontumor cases included three parainfectious and two idiopathic cases. The median time from symptom onset to diagnosis was 34 days. All patients with diagnostic OMS criteria in the idiopathic, nontumor group underwent whole-exome sequencing, with potentially pathogenic mutations identified in two cases. Nine patients were treated with methylprednisolone pulse, followed by oral steroids; eight received one or more intravenous immunoglobulin treatments; and six received azathioprine and cyclophosphamide. Complete symptomatic recovery was observed in only one patient. CONCLUSIONS: OMS diagnosis remains challenging. Diagnostic suspicion is necessary to improve the management of these patients and allow early immunosuppressive treatment. Paraneoplastic etiology is the most prevalent. In idiopathic patients who do not respond to immunosuppressive treatment, tests, such as whole-exome sequencing, may reveal a differential diagnosis. Genetic alterations that increase the risk of tumors may be an important clue to the pathophysiology of OMS.

Phenotypic and transcriptional characterization of F. tularensis LVS during transition into a viable but non-culturable state.

Francisella tularensis is a gram-negative, intracellular pathogen which can cause serious, potentially fatal, illness in humans. Species of F. tularensis are found across the Northern Hemisphere and can infect a broad range of host species, including humans. Factors affecting the persistence of F. tularensis in the environment and its epidemiology are not well understood, however, the ability of F. tularensis to enter a viable but non-culturable state (VBNC) may be important. A broad range of bacteria, including many pathogens, have been observed to enter the VBNC state in response to stressful environmental conditions, such as nutrient limitation, osmotic or oxidative stress or low temperature. To investigate the transition into the VBNC state for F. tularensis, we analyzed the attenuated live vaccine strain, F. tularensis LVS grown under standard laboratory conditions. We found that F. tularensis LVS rapidly and spontaneously enters a VBNC state in broth culture at 37°C and that this transition coincides with morphological differentiation of the cells. The VBNC bacteria retained an ability to interact with both murine macrophages and human erythrocytes in in vitro assays and were insensitive to treatment with gentamicin. Finally, we present the first transcriptomic analysis of VBNC F. tularensis, which revealed clear differences in gene expression, and we identify sets of differentially regulated genes which are specific to the VBNC state. Identification of these VBNC specific genes will pave the way for future research aimed at dissecting the molecular mechanisms driving entry into the VBNC state.

Psychobehavioral factors and family functioning in mucopolysaccharidosis: preliminary studies.

Introduction: Mucopolysaccharidoses (MPS) constitute a group of progressive and multisystemic inherited metabolic diseases that profoundly affect both the mental health of patients and the wellbeing of their families. This study aims to evaluate the impact of MPS on family functioning and related factors. Methods and results: Twenty-five patients with MPS, including types I (n = 4), II (n = 11), IIIB (n = 2), IVA (n = 3), and VI (n = 5), and their families participated in this study. The mean patient age was 13 years [standard deviation (SD): 7.7 years]. Behavioral and emotional problems were noted in 9.1% of all patients. While the type of MPS did not directly influence mental problems, the presence of neuronal involvement did (p = 0.006). Patients with MPS III exhibited difficulties primarily in emotional areas, conduct, hyperactivity, and peer problems. Importantly, both patients with MPS II and those with MPS III experienced a significant impact on communication [mean scores for communication domain: MPS II, 35.6 (SD: 24.3); MPS III, 35.0 (SD: 22.6)]; poorer communication was directly linked to worse adaptive behavior (p = 0.012), and worse adaptive behavior was associated with lower quality of life (p = 0.001). Quality of life and caregiver burden among family members did not significantly differ across MPS types; however, higher caregiver burden was negatively associated with quality of life (p = 0.002). Concerning family functioning, the most impacted domains included independence, intellectual/cultural orientation, activity/recreation, and expressiveness. Domain scores did not vary based on MPS type, treatment, or neurological involvement. Quality-of-life scores were positively associated with the cultural/intellectual domain score. Conclusion: The impacts of quality of life and family extend beyond clinical characteristics and MPS type, strongly influenced by patient cognition and communication, as well as type of family functioning, especially those with greater cultural/intellectual skills of their family members. A multidisciplinary approach addressing the broader needs of individuals with MPS becomes essential. Techniques aimed at improving communication, including prompt interventions such as speech therapy and augmentative and alternative communication strategies, can contribute to overall family functioning improvement.

A Shadow of Doubt: Is There Implicit Bias Among Orthopaedic Surgery Faculty and Residents Regarding Race and Gender?

BACKGROUND: Orthopaedic surgery continues to be one of the least diverse medical specialties. Recently, increasing emphasis has been placed on improving diversity in the medical field, which includes the need to better understand existing biases. Despite this, only about 6% of orthopaedic surgeons are women and 0.3% are Black. Addressing diversity, in part, requires a better understanding of existing biases. Most universities and residency programs have statements and policies against discrimination that seek to eliminate explicit biases. However, unconscious biases might negatively impact the selection, training, and career advancement of women and minorities who are underrepresented in orthopaedic surgery. Although this is difficult to measure, the Implicit Association Test (IAT) by Project Implicit might be useful to identify and measure levels of unconscious bias among orthopaedic surgeons, providing opportunities for additional interventions to improve diversity in this field. QUESTIONS/PURPOSES: (1) Do orthopaedic surgeons demonstrate implicit biases related to race and gender roles? (2) Are certain demographic characteristics (age, gender, race or ethnicity, or geographic location) or program characteristics (geographic location or size of program) associated with the presence of implicit biases? (3) Do the implicit biases of orthopaedic surgeons differ from those of other healthcare providers or the general population? METHODS: A cross-sectional study of implicit bias among orthopaedic surgeons was performed using the IAT from Project Implicit. The IAT is a computerized test that measures the time required to associate words or pictures with attributes, with faster or slower response times suggesting the ease or difficulty of associating the items. Although concerns have been raised recently about the validity and utility of the IAT, we believed it was the right study instrument to help identify the slight hesitation that can imply differences between inclusion and exclusion of a person. We used two IATs, one for Black and White race and one for gender, career, and family roles. We invited a consortium of researchers from United States and Canadian orthopaedic residency programs. Researchers at 34 programs agreed to distribute the invitation via email to their faculty, residents, and fellows for a total of 1484 invitees. Twenty-eight percent (419) of orthopaedic surgeons and trainees completed the survey. The respondents were 45% (186) residents, 55% (228) faculty, and one fellow. To evaluate response biases, the respondent population was compared with that of the American Academy of Orthopaedic Surgeons census. Responses were reported as D-scores based on response times for associations. D-scores were categorized as showing strong (≥ 0.65), moderate (≥ 0.35 to < 0.65), or slight (≥ 0.15 to < 0.35) associations. For a frame of reference, orthopaedic surgeons' mean IAT scores were compared with historical scores of other self-identified healthcare providers and that of the general population. Mean D-scores were analyzed with the Kruskal-Wallis test to determine whether demographic characteristics were associated with differences in D-scores. Bonferroni correction was applied, and p values less than 0.0056 were considered statistically significant. RESULTS: Overall, the mean IAT D-scores of orthopaedic surgeons indicated a slight preference for White people (0.29 ± 0.4) and a slight association of men with career (0.24 ± 0.3), with a normal distribution. Hence, most respondents' scores indicated slight preferences, but strong preferences for White race were noted in 27% (112 of 419) of respondents. There was a strong association of women with family and home and an association of men with work or career in 14% (60 of 419). These preferences generally did not correlate with the demographic, geographic, and program variables that were analyzed, except for a stronger association of women with family and home among women respondents. There were no differences in race IAT D-scores between orthopaedic surgeons and other healthcare providers and the general population. Gender-career IAT D-scores associating women with family and home were slightly lower among orthopaedic surgeons (0.24 ± 0.3) than among the general population (0.32 ± 0.4; p < 0.001) and other healthcare professionals (0.34 ± 0.4; p < 0.001). All of these values are in the slight preference range. CONCLUSION: Orthopaedic surgeons demonstrated slight preferences for White people, and there was a tendency to associate women with career and family on IATs, regardless of demographic and program characteristics, similar to others in healthcare and the general population. Given the similarity of scores with those in other, more diverse areas of medicine, unconscious biases alone do not explain the relative lack of diversity in orthopaedic surgery. CLINICAL RELEVANCE: Implicit biases only explain a small portion of the lack of progress in improving diversity, equity, inclusion, and belonging in our workforce and resolving healthcare disparities. Other causes including explicit biases, an unwelcoming culture, and perceptions of our specialty should be examined. Remedies including engagement of students and mentorship throughout training and early career should be sought.

Alternative splice variants of the mitochondrial fission protein DNM1L/Drp1 regulate mitochondrial dynamics and tumor progression in ovarian cancer.

Aberrant mitochondrial fission/fusion dynamics have been reported in cancer cells. While post translational modifications are known regulators of the mitochondrial fission/fusion machinery, we show that alternative splice variants of the fission protein Drp1 (DNM1L) have specific and unique roles in cancer, adding to the complexity of mitochondrial fission/fusion regulation in tumor cells. Ovarian cancer specimens express an alternative splice transcript variant of Drp1 lacking exon 16 of the variable domain, and high expression of this splice variant relative to other transcripts is associated with poor patient outcome. Unlike the full-length variant, expression of Drp1 lacking exon 16 leads to decreased association of Drp1 to mitochondrial fission sites, more fused mitochondrial networks, enhanced respiration, and TCA cycle metabolites, and is associated with a more metastatic phenotype in vitro and in vivo. These pro-tumorigenic effects can also be inhibited by specific siRNA-mediated inhibition of the endogenously expressed transcript lacking exon 16. Moreover, lack of exon 16 abrogates mitochondrial fission in response to pro-apoptotic stimuli and leads to decreased sensitivity to chemotherapeutics. These data emphasize the significance of the pathophysiological consequences of Drp1 alternative splicing and divergent functions of Drp1 splice variants, and strongly warrant consideration of Drp1 splicing in future studies.

Psychometric properties of the PTSD checklist for DSM-5 in treatment-seeking Black veterans.

OBJECTIVE: Despite widespread use of the posttraumatic stress disorder (PTSD) Checklist for Diagnostic and Statistical Manual of Mental Disorders-fifth edition (PCL-5) across various trauma-exposed populations, little is known about the psychometric properties of the instrument in certain ethnic minority groups with increased risk of trauma exposure, including Black veterans. To this end, the current study examined the internal consistency of the PCL-5, convergent validity using correlations between the PCL-5 and another measure of PTSD, and discriminant validity using correlations between the PCL-5 and other commonly occurring psychiatric symptoms, including depression as well as alcohol and substance misuse. METHOD: The sample was composed of 327 Black veterans (84% male, Mage = 51.87, SD = 13.72) presenting to a PTSD specialty clinic at a large Veterans Affairs hospital in the Midwest United States to receive psychological services. In addition to a diagnostic interview, veterans were asked to complete a brief battery of self-report questionnaires to assist with diagnostic clarification and treatment planning. RESULTS: The PCL-5 demonstrated excellent internal consistency. Furthermore, the PCL-5 was significantly and positively correlated with PTSD diagnostic status, suggesting evidence of convergent validity. Finally, the PCL-5 was strongly correlated with symptoms of depression and moderately correlated with alcohol and substance misuse. CONCLUSIONS: Findings suggest that the PCL-5 is a psychometrically sound measure to assess PTSD symptoms among Black veterans. Considering the brevity of PCL-5 administration, clinicians should consider utilizing this and other psychometric tests in clinical care to reduce disparities in health equity among Black patients. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Bio-based polyester-polyurethane foams: synthesis and degradability by Aspergillus niger and Aspergillus clavatus.

In this article, the degradability by Aspergillus niger and Aspergillus clavatus of three bio-based polyurethane (PU) foams is compared to previous degradability studies involving a Pseudomonas sp. bacterium and similar initial materials (Spontón et al. in Int. Biodet. Biodeg. 85:85-94, 2013, https://doi.org/10.1016/j.ibiod.2013.05.019 ). First, three new polyester-polyurethane foams were prepared from mixtures of castor oil (CO), maleated castor oil (MACO), toluene diisocyanate (TDI), and water. Then, their degradation tests were carried out in an aqueous medium, and employing the two mentioned fungi, after their isolation from the environment. From the degradation tests, the following was observed: (a) the insoluble (and slightly collapsed) foams exhibited free hydroxyl, carboxyl, and amine moieties; and (b) the water soluble (and low molar mass) compounds contained amines, carboxylic acids, and glycerol. The most degraded foam contained the highest amount of MACO, and therefore the highest concentration of hydrolytic bonds. A basic biodegradation mechanism was proposed that involves hydrolysis and oxidation reactions.

Capturing the Range of Disease Involvement in Localized Scleroderma: The Localized Scleroderma Total Severity Scale.

OBJECTIVE: Juvenile localized scleroderma (jLS) is a chronic autoimmune disease commonly associated with poor outcomes, including contractures, hemiatrophy, uveitis, and seizures. Despite improvements in treatment, >25% of patients with jLS have functional impairment. To improve patient evaluation, our workgroup developed the Localized scleroderma Total Severity Scale (LoTSS), an overall disease severity measure. METHODS: LoTSS was developed as a weighted measure by a consensus process involving literature review, surveys, case vignettes, and multicriteria decision analysis. Feasibility was assessed in larger Childhood Arthritis and Rheumatology Research Alliance groups. Construct validity with physician assessment and inter-rater reliability was assessed using case vignettes. Additional evaluation was performed in a prospective patient cohort initiating treatment. RESULTS: LoTSS severity items were organized into modules that reflect jLS disease patterns, with modules for skin, extracutaneous, and craniofacial manifestations. Construct validity of LoTSS was supported by a strong positive correlation with the Physician Global Assessment (PGA) of severity and damage and weak positive correlation with PGA-Activity, as expected. LoTSS was responsive, with a small effect size identified. Moderate-to-excellent inter-rater reliability was demonstrated. LoTSS was able to discriminate between patient subsets, with higher scores identified in those with greater disease burden and functional limitation. CONCLUSION: We developed a new LS measure for assessing cutaneous and extracutaneous severity and have shown it to be reliable, valid, and responsive. LoTSS is the first measure that assesses and scores all the major extracutaneous manifestations in LS. Our findings suggest LoTSS could aid assessment and management of patients and facilitate outcome evaluation in treatment studies.

Cross-protection and cross-neutralization capacity of ancestral and VOC-matched SARS-CoV-2 adenoviral vector-based vaccines.

COVID-19 vaccines were originally designed based on the ancestral Spike protein, but immune escape of emergent Variants of Concern (VOC) jeopardized their efficacy, warranting variant-proof vaccines. Here, we used preclinical rodent models to establish the cross-protective and cross-neutralizing capacity of adenoviral-vectored vaccines expressing VOC-matched Spike. CoroVaxG.3-D.FR, matched to Delta Plus Spike, displayed the highest levels of nAb to the matched VOC and mismatched variants. Cross-protection against viral infection in aged K18-hACE2 mice showed dramatic differences among the different vaccines. While Delta-targeted vaccines fully protected mice from a challenge with Gamma, a Gamma-based vaccine offered only partial protection to Delta challenge. Administration of CorovaxG.3-D.FR in a prime/boost regimen showed that a booster was able to increase the neutralizing capacity of the sera against all variants and fully protect aged K18-hACE2 mice against Omicron BA.1, as a BA.1-targeted vaccine did. The neutralizing capacity of the sera diminished in all cases against Omicron BA.2 and BA.5. Altogether, the data demonstrate that a booster with a vaccine based on an antigenically distant variant, such as Delta or BA.1, has the potential to protect from a wider range of SARS-CoV-2 lineages, although careful surveillance of breakthrough infections will help to evaluate combination vaccines targeting antigenically divergent variants yet to emerge.

Co-Occurring Posttraumatic Stress Disorder Symptoms and Alcohol Use Behaviors: The Mediating Role of Drinking to Cope with PTSD Symptoms.

OBJECTIVE: Posttraumatic stress disorder (PTSD) symptoms and hazardous drinking often co-occur. One widely acknowledged explanation for this co-occurrence is the self-medication hypothesis. However, only one study to date has explicitly examined the extent to which drinking to cope with trauma-related symptoms, rather than drinking to cope with negative affect more broadly, accounts for this association. METHOD: Survey data were collected from a nationally representative sample of adults (n = 360; 48.9% female, Mage = 38.50 years, SD = 10.23). RESULTS: Results revealed a significant indirect effect of PTSD symptom severity on alcohol use frequency and alcohol use-related problems via drinking to cope with PTSD symptoms but not alcohol use quantity or binge drinking frequency. Drinking to cope with negative affect did not indirectly mediate the relations between PTSD symptom severity and any of the alcohol use-related outcomes. CONCLUSIONS: Findings will be discussed with regard to previous and future research.