Sequential early-life viral infections modulate the microbiota and adaptive immune responses to systemic and mucosal vaccination.

Increasing evidence points to the microbial exposome as a critical factor in maturing and shaping the host immune system, thereby influencing responses to immune challenges such as infections or vaccines. To investigate the effect of early-life viral exposures on immune development and vaccine responses, we inoculated mice with six distinct viral pathogens in sequence beginning in the neonatal period, and then evaluated their immune signatures before and after intramuscular or intranasal vaccination against SARS-CoV-2. Sequential viral infection drove profound changes in all aspects of the immune system, including increasing circulating leukocytes, altering innate and adaptive immune cell lineages in tissues, and markedly influencing serum cytokine and total antibody levels. Beyond changes in the immune responses, these exposures also modulated the composition of the endogenous intestinal microbiota. Although sequentially-infected mice exhibited increased systemic immune activation and T cell responses after intramuscular and intranasal SARS-CoV-2 immunization, we observed decreased vaccine-induced antibody responses in these animals. These results suggest that early-life viral exposures are sufficient to diminish antibody responses to vaccination in mice, and highlight the potential importance of considering prior microbial exposures when investigating vaccine responses.

The effect of ankle-foot orthoses on gait characteristics in people with Charcot-Marie-Tooth disease: A systematic review and meta-analysis.

INTRODUCTION: Ankle-foot orthoses (AFOs) are commonly prescribed for people with Charcot-Marie-Tooth disease (CMT) to improve gait efficiency and reduce the occurrence of tripping and falls. The aim of this study was to systematically review evidence on the effects of AFOs on gait kinematics and kinetics and postural stability/balance in people with CMT. METHODS: Studies were identified from electronic databases and screened for inclusion online using Rayyan. Data from all eligible studies were extracted into a standardised Excel spreadsheet. Methodological quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklists. Where available, continuous outcomes were pooled to estimate standardised mean differences in random-effects meta-analyses. RESULTS: A total of 15 studies were included with variable methodological quality. Sample sizes ranged from 1 to 32 with significant variability in participant characteristics, AFO designs and testing procedures. Data from eight studies were available for meta-analysis. Although AFOs impacted walking velocity, stride length, step length, cadence, ankle dorsiflexion, plantarflexion, knee and hip flexion and ankle plantarflexion and dorsiflexion moments, the effect sizes were small-to-moderate and non-significant. There were insufficient data available for pooled analyses of outcomes related to postural stability/balance. CONCLUSION: Although AFOs positively affect a number of gait and balance parameters, the small participant numbers, variability in participant characteristics, AFO designs and testing procedures adopted by the available studies resulted in the absence of statistically significant effects when data were pooled. The results from this review also highlight the importance of device customisation based on the individual needs of people with CMT and their degree of gait impairment.

Arg92Leu-cTnT Alters the cTnC-cTnI Interface Disrupting PKA-Mediated Relaxation.

BACKGROUND: Impaired left ventricular relaxation, high filling pressures, and dysregulation of Ca2+ homeostasis are common findings contributing to diastolic dysfunction in hypertrophic cardiomyopathy (HCM). Studies have shown that impaired relaxation is an early observation in the sarcomere-gene-positive preclinical HCM cohort, which suggests the potential involvement of myofilament regulators in relaxation. A molecular-level understanding of mechanism(s) at the level of the myofilament is lacking. We hypothesized that mutation-specific, allosterically mediated, changes to the cTnC (cardiac troponin C)-cTnI (cardiac troponin I) interface can account for the development of early-onset diastolic dysfunction via decreased PKA accessibility to cTnI. METHODS: HCM mutations R92L-cTnT (cardiac troponin T; Arg92Leu) and Δ160E-cTnT (Glu160 deletion) were studied in vivo, in vitro, and in silico via 2-dimensional echocardiography, Western blotting, ex vivo hemodynamics, stopped-flow kinetics, time-resolved fluorescence resonance energy transfer, and molecular dynamics simulations. RESULTS: The HCM-causative mutations R92L-cTnT and Δ160E-cTnT result in different time-of-onset diastolic dysfunction. R92L-cTnT demonstrated early-onset diastolic dysfunction accompanied by a localized decrease in phosphorylation of cTnI. Constitutive phosphorylation of cTnI (cTnI-D23D24) was sufficient to recover diastolic function to non-Tg levels only for R92L-cTnT. Mutation-specific changes in Ca2+ dissociation rates associated with R92L-cTnT reconstituted with cTnI-D23D24 led us to investigate potential involvement of structural changes in the cTnC-cTnI interface as an explanation for these observations. We probed the interface via time-resolved fluorescence resonance energy transfer revealing a repositioning of the N-terminus of cTnI, closer to cTnC, and concomitant decreases in distance distributions at sites flanking the PKA consensus sequence. Implementing time-resolved fluorescence resonance energy transfer distances as constraints into our atomistic model identified additional electrostatic interactions at the consensus sequence. CONCLUSIONS: These data show that the early diastolic dysfunction observed in a subset of HCM is attributable to allosterically mediated structural changes at the cTnC-cTnI interface that impair accessibility of PKA, thereby blunting ß-adrenergic responsiveness and identifying a potential molecular target for therapeutic intervention.

Tubulointerstitial Nephritis and Uveitis Syndrome: A Case Report.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is an uncommon autoimmune disorder that is defined by tubulointerstitial nephritis and uveitis. It is frequently underdiagnosed or goes unrecognized due to the challenges of accurately diagnosing the syndrome. TINU has mostly been seen among female pediatric patients with primarily bilateral anterior uveitis. However, screening for kidney disease often is overlooked; therefore, it is important for ophthalmologists, nephrologists, and rheumatologists to routinely screen for kidney disease and have TINU as a differential. We present a case of an adult female who had bilateral anterior uveitis for several years and then was found to have advanced chronic kidney disease, showing tubulointerstitial nephritis (TIN) features on renal biopsy.

Comparative Review of Standardized Incidence Ratio of Nonlymphoid, De Novo Malignancies After Liver Transplant Versus After Kidney Transplant.

OBJECTIVES: De novo malignancies are the most common cause of death after solid-organ transplant. Here, we aimed to summarize standard incidence ratios of de novo malignancies after liver and kidney transplant within the same geographical locations, compare these ratios among differenttypes of de novo malignancies after liver and kidney transplant, and elucidate differences in de novo malignancies between liver and kidney transplant recipients. MATERIALS AND METHODS: We performed a systematic review to identify studies on standard incidence ratios of de novo malignancies after liver and kidney transplant in the United Kingdom, Sweden, South Korea, and Taiwan. RESULTS: Four articles reported standard incidence ratios of de novo malignancies in 14 016 liver transplant recipients (mean follow-up 4.3 ± 0.7 y) and 48179 kidney transplant recipients (mean follow-up 6.1 ± 2.1 y). Mean ratios of oropharyngeal, pulmonary, colorectal, renal, and breast malignancies were 5.3, 1.6, 1.9, 1.8, and 1.1,respectively, after liver transplant and 3.2, 1.7, 1.5, 17.0, and 1.3, respectively, after kidney transplant. Mean ratios of bladder, cervixuterus, and stomach de novo malignancies were 1.8, 2.0, and 2.9, respectively, after liver transplant and 13.0, 1.9, and 1.9,respectively, after kidney transplant. Mean ratios of prostatic and esophageal malignancies were 1.6 and 1.8 after liver transplant and 1.2 and 1.1 after kidney transplant. Mean ratio of ovarian cancer was 1.2 and 2.9, respectively, after liver and kidney transplant. CONCLUSIONS: Low-frequency and lower standard incidence ratios were observed for testicular, ovarian and central nervous system malignancies after kidney and liver transplant. Standard incidence ratios of oropharyngeal and hepatic malignancies were higher after liver transplant compared with kidney transplant. After kidney transplant, standardized ration for renal malignancy were 9.4 times and bladder malignancies were 7.2 times higher compared with liver transplant recipients.

A Comparison of Demographic Diversity Between Orthopaedic Surgery Residents and ACGME Foot and Ankle Fellows From 2007 to 2022.

Background: Academic medicine emphasizes the need to recruit a diverse workforce in graduate medical education. Orthopaedic surgery residency has demonstrated efforts to model program compositions with evolving US demographics. However, it remains unclear whether orthopaedic fellowships, particularly foot and ankle, also reflect these efforts. Methods: Using the publicly available Accreditation Council for Graduate Medical Education (ACGME) Data Resource Book, a census of the gender and racial/ethnic identities of orthopaedic foot and ankle fellows, as well as active orthopaedic surgery residents, were compiled from 2007 to 2022. Linear trend analysis was conducted to evaluate the trends of orthopaedic residents and foot and ankle fellows, with a Pearson correlation for comparison. Results: Prior analysis demonstrated no significant change in sex and ethnic diversity of fellows from 2006 to 2015. The majority of foot and ankle fellows were White (31%-69%) and male (63%-88%). Linear analysis demonstrated growing diversity in female and non-White active orthopaedic surgery residents. Similarly, there was an increasing number of female foot and ankle fellows (0%-38%) reflective of the trend in orthopaedic residency (12%-20%); however, there was no significant change among racial/ethnic identities. Pearson correlation analysis between the trend of orthopaedic residency residents and foot and ankle fellows suggests moderate correlation among female, Asian, and "Unknown" racial/ethnic categories. Conclusion: The proportion of foot and ankle female fellows in ACGME-accredited fellowships has matched or exceeded the percentage of female orthopaedic residents. Despite increased diversity of orthopaedic surgery residents over the past 2 decades, ACGME-accredited foot and ankle fellowships do not yet reflect similar trends among racial/ethnic minorities. Level of Evidence: Level III, retrospective cohort study.

Thoracolumbar fusions for adult lumbar deformity show superior QALY gain and lower costs compared with upper thoracic fusions.

PURPOSE: Adult spinal deformity (ASD) patients with sagittal plane deformity (N) or structural lumbar/thoraco-lumbar (TL) curves can be treated with fusions stopping at the TL junction or extending to the upper thoracic (UT) spine. This study evaluates the impact on cost/cumulative quality-adjusted life year (QALY) in patients treated with TL vs UT fusion. METHODS: ASD patients with > 4-level fusion and 2-year follow-up were included. Index and total episode-of-care costs were estimated using average itemized direct costs obtained from hospital records. Cumulative QALY gained were calculated from preoperative to 2-year postoperative change in Short Form Six-Dimension (SF-6D) scores. The TL and UT groups comprised patients with upper instrumented vertebrae (UIV) at T9-T12 and T2-T5, respectively. RESULTS: Of 566 patients with type N or L curves, mean age was 63.2 ± 12.1 years, 72% were female and 93% Caucasians. Patients in the TL group had better sagittal vertical axis (7.3 ± 6.9 vs. 9.2 ± 8.1 cm, p = 0.01), lower surgical invasiveness (- 30; p < 0.001), and shorter OR time (- 35 min; p = 0.01). Index and total costs were 20% lower in the TL than in the UT group (p < 0.001). Cost/QALY was 65% lower (492,174.6 vs. 963,391.4), and 2-year QALY gain was 40% higher, in the TL than UT group (0.15 vs. 0.10; p = 0.02). Multivariate model showed TL fusions had lower total cost (p = 0.001) and higher QALY gain (p = 0.03) than UT fusions. CONCLUSION: In Schwab type N or L curves, TL fusions showed lower 2-year cost and improved QALY gain without increased reoperation rates or length of stay than UT fusions. LEVEL OF EVIDENCE: III.

Agomelatine Is Unable to Attenuate Kainic Acid-Induced Deficits in Early Life Communicative Behavior.

Early life seizures are associated with a variety of behavioral comorbidities. Among the most prevalent of these are deficits in communication. Auditory communicative behaviors in mice, known as ultrasonic vocalizations (USVs), can be used to assess potential treatments. Agomelatine is a melatonin agonist that effectively reduces behavioral comorbidities of seizures in adults; however, its ability to attenuate seizure-induced communicative deficits in neonates is unknown. To address this, we administered C57 mice either saline or kainic acid (KA) on postnatal day (PD) 10. The mice then received either agomelatine or saline 1-h post-status epilepticus. On PD 11, we assessed the quantity of USVs produced, the duration, peak frequency, fundamental frequency, and amplitude of the vocalizations, as well as the call type utilization. We found that KA increased vocal production and reduced USV variability relative to controls. KA also increased USV duration and amplitude and significantly altered the types of calls produced. Agomelatine did not attenuate any of the deficits. Our study is the first to assess agomelatine's efficacy to correct USVs and thus provides an important point of context to the literature, indicating that despite its high therapeutic efficacy to attenuate other behavioral comorbidities of seizures, agomelatine's ability to correct neonatal communicative deficits is limited.

A Comparative Review of Standardized Incidence Ratios of De Novo Malignancies Post Liver Transplantation in Males Versus Females.

After liver transplantation (LTx), the most common cause of death in the long-term is de-novo malignancy (DNM). The aim is to review the gender differences in the standardized incidence ratio (SIR) of DNM within the same geographical locations. METHODS: Four studies were identified comparing post-LTx SIR between males and females. RESULTS: From 6663 males and 2780 females LTx recipients, the mean SIR from each of the four studies for males is 2.8, 2.0, 1.94, and 3.4, and 3.5, 1.3, 1.95, and 2.3 for females. On meta-analysis using a random effect model for each gender group. No significant difference was revealed after logarithmic transformation and subgroup meta-analysis. Overall mean SIR with 95% Confidence Interval (CI) for males is 2.53 (95% CI 1.65-3.88) and 2.3 (1.25-4.24) for females. lung malignancy, 1.97 (1.14-3.41) for males and 2.65 (0.67-10.47) for females. For colorectal malignancy, the combined SIR for males is 1.98 (0.58-6.78) and 1.85 (1.02-3.37) for females. The SIR for female gender-specific malignancies; SIR for breast is 1.1 ± 4.4, cervix 2.9 ± 1.9, uterus 2.8, and ovarian 0.7, and for males, testis 1.6 ± 1.3, prostate 1.2 ± 0.4. However, rare malignancies, male breast cancers (n = 1, SIR, 22.6), and Kaposi's sarcoma, in males (n = 6) and in females (n = 1), had SIR 120. and 212.7, respectively. CONCLUSION: Overall, there are no statistical differences between male and female DNM. Female-specific cervix, uterus, ovarian, and male-specific testis and prostate have similar SIR. Rare malignancies have very high SIR.

A multi-biomarker panel for predicting Tocilizumab response in Rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammation in the synovial lining of the joints. Key inflammatory cytokines such as interleukin-6 (IL-6), TNF-α, and others play a critical role in the activation of local synovial leukocytes and the induction of chronic inflammation. Tocilizumab (TCZ), a humanized anti-IL-6 receptor monoclonal antibody, has demonstrated significant clinical efficacy in treating RA patients. However, similar to other inflammatory cytokine blockers, such as TNF-alpha inhibitors, Interleukin-1 inhibitors, or CD20 inhibitors, some patients do not respond to treatment. To address this challenge, our study employed a high-precision proteomics approach to identify protein biomarkers capable of predicting clinical responses to Tocilizumab in RA patients. Through the use of data-independent acquisition (DIA) mass spectrometry, we analyzed serum samples from both TCZ responders and non-responders to discover potential biomarker candidates. These candidates were subsequently validated using individual serum samples from two independent cohorts: a training set (N = 70) and a test set (N = 18), allowing for the development of a robust multi-biomarker panel. The constructed multi-biomarker panel demonstrated an average discriminative power of 86 % between response and non-response groups, with a high area under the curve (AUC) value of 0.84. Additionally, the panel exhibited 100 % sensitivity and 60 % specificity. Collectively, our multi-biomarker panel holds promise as a diagnostic tool to predict non-responders to TCZ treatment in RA patients.

Caregiver preferences for physically harsh discipline of children in rural Uganda.

Purpose: Physically harsh discipline is associated with poor developmental outcomes among children. These practices are more prevalent in areas experiencing poverty and resource scarcity, including in low- and middle-income countries. Designed to limit social desirability bias, this cross-sectional study in rural Uganda estimated caregiver preferences for physically harsh discipline; differences by caregiver sex, child sex, and setting; and associations with indicators of household economic stress and insecurity. Method: Three-hundred-fifty adult caregivers were shown six hypothetical pictographic scenarios depicting children whining, spilling a drink, and kicking a caregiver. Girls and boys were depicted engaging in each of the three behaviors. Approximately half of the participants were shown scenes from a market setting and half were shown scenes from a household setting. For each scenario, caregivers reported the discipline strategy they would use (time out, beating, discussing, yelling, ignoring, slapping). Results: Two thirds of the participants selected a physically harsh discipline strategy (beating, slapping) at least once. Women selected more physically harsh discipline strategies than men (b = 0.40; 95% confidence interval [CI], 0.26 to 0.54). Participants shown scenes from the market selected fewer physically harsh discipline strategies than participants shown scenes from the household (b = -0.51; 95% CI, -0.69 to -0.33). Finally, caregivers selected more physically harsh discipline strategies in response to boys than girls. Indicators of economic insecurity were inconsistently associated with preferences for physically harsh discipline. Conclusions: The high prevalence of physically harsh discipline preferences warrant interventions aimed at reframing caregivers' approaches to discipline.

Biomechanical, biochemical, and histological characterization of sacroiliac joint cartilage in the Yucatan minipig.

Although the sacroiliac (SI) joint can be a source of lower back and buttock pain, no comprehensive characterization studies on SI cartilage have been conducted. Using the minipig as a large animal model, this study conducted the first biomechanical, biochemical, and histological characterization of SI joint cartilage. Because previous literature has reported that sacral cartilage and iliac cartilage within the SI joint are histologically distinct, concomitantly it was expected that functional properties of the sacral cartilage would differ from those of the iliac cartilage. Creep indentation, uniaxial tension, biochemical, and histological analyses were conducted on the sacral and iliac cartilage of skeletally mature female Yucatan minipigs (n = 6-8 for all quantitative tests). Concurring with prior literature, the iliac cartilage appeared to be more fibrous than the sacral cartilage. Glycosaminoglycan content was 2.2 times higher in the sacral cartilage. The aggregate modulus of the sacral cartilage was 133 ± 62 kPa, significantly higher than iliac cartilage, which only had an aggregate modulus of 51 ± 61 kPa. Tensile testing was conducted in both cranial-caudal and ventral-dorsal axes, and Young's modulus values ranged from 2.5 ± 1.5 MPa to 13.6 ± 1.5 MPa, depending on anatomical structure (i.e., sacral vs. iliac) and orientation of the tensile test. The Young's modulus of sacral cartilage was 5.5 times higher in the cranial-caudal axis and 2.0 times higher in the ventral-dorsal axis than the iliac cartilage. The results indicate that the sacral and iliac cartilages are functionally distinct from each other. Understanding the distinct differences between sacral and iliac cartilage provides insight into the structure and function of the SI joint, which may inform future research aimed at repairing SI joint cartilage.

Cerebrospinal Fluid Leaks: Challenges in Localizing Spontaneous Spinal Leak Sites and Minimally Invasive Treatment.

The confirmation of cerebrospinal fluid (CSF) leaks in the setting of spontaneous intracranial hypotension (SIH) by imaging involves a growing toolset of multimodal advanced spinal and skull base imaging techniques, for which exists a unique set of challenges for each CSF leak type. Furthermore, the repertoire of minimally invasive CSF leak treatment beyond nontargeted epidural blood patch administration has grown widely, with varied practices across institutions. This review describes current diagnostic imaging and treatment modalities as they apply to the challenges of CSF leak localization and management.

Radiographic and Clinical Outcomes of Transverse Process Hook Placement at the Proximal Thoracic Upper Instrumented Vertebra in Adult Spinal Deformity Surgery.

OBJECTIVE: Few studies have reported radiographic and clinical outcomes of transverse process hook (TPH) placement at the proximal thoracic upper instrumented vertebra (UIV) in adult spinal deformity (ASD) surgery. This study aims to investigate radiographic and clinical outcomes of TPH placement at the UIV for ASD surgery. METHODS: This is a retrospective cohort of 56 patients with ASD (age, 59 ± 13 years; followup, 44 ± 19 months) from Johns Hopkins Hospital, who underwent long posterior spinal fusion to the proximal thoracic spine (T2-5). Visual analogue scale (VAS) for back pain, Oswestry Disability Index (ODI), 36-item Short Form health survey scores, thoracic kyphosis (TK), lumbar lordosis, sacral slope, pelvic tilt, pelvic incidence, proximal junctional kyphosis (PJK) angle, PJK incidence, pattern of PJK, grades of TPH dislodgement, revision surgery, and factors associated with high-grade TPH dislodgement were analyzed. RESULTS: VAS for back pain and ODI values improved significantly from preoperatively to final follow-up. Mean change in PJK angle was 12° (range, 0.5°-43°). Twenty patients (36%) developed PJK, of whom 13 had compression fractures at 1 vertebra distal to the UIV (UIV-1). Final TPH position was stable in 42 patients (75%). In most patients (86%), TPH dislodgement did not progress after 6-month postoperative follow-up. Three patients (5.3%) underwent revision surgery to extend the fusion because of symptomatic PJK. Unstable TPH position was associated only with revision surgery and TK. CONCLUSION: TPH placement at the proximal thoracic UIV for long fusion showed favorable clinical and radiographic outcomes in terms of the incidence of PJK and mean PJK angle at mean 44-month follow-up. TPHs placed in the proximal thoracic UIV were in stable position in 75% of patients. Compression fracture at UIV-1 was the most common pattern of PJK. PJK angle progression was greater in revision cases and in patients with greater preoperative thoracic kyphosis.

Low bone mineral density: a primer for the spine surgeon.

Within spinal surgery, low bone mineral density is associated with several postoperative complications, such as proximal junctional kyphosis, pseudoarthrosis, and screw loosening. Although modalities such as CT and MRI can be utilized to assess bone quality, DEXA scans, the "Gold Standard" for diagnosing osteoporosis, is not routinely included in preoperative workup. With an increasing prevalence of osteoporosis in an aging population, it is critical for spine surgeons to understand the importance of evaluating bone mineral density preoperatively to optimize postoperative outcomes. The purpose of this state-of-the-art review is to provide surgeons a summary of the evaluation, treatment, and implications of low bone mineral density in patients who are candidates for spine surgery.

Inhibition of mast cell degranulation by novel small molecule MRGPRX2 antagonists.

BACKGROUND: Mas-related G protein-coupled receptor X2 (MRGPRX2) is a promiscuous receptor on mast cells that mediates IgE-independent degranulation and has been implicated in multiple mast cell-mediated disorders, including chronic urticaria, atopic dermatitis, and pain disorders. Although it is a promising therapeutic target, few potent, selective, small molecule antagonists have been identified, and functional effects of human MRGPRX2 inhibition have not been evaluated in vivo. OBJECTIVE: We sought to identify and characterize novel, potent, and selective orally active small molecule MRGPRX2 antagonists for potential treatment of mast cell-mediated disease. METHODS: Antagonists were identified using multiple functional assays in cell lines overexpressing human MRGPRX2, LAD2 mast cells, human peripheral stem cell-derived mast cells, and isolated skin mast cells. Skin mast cell degranulation was evaluated in Mrgprb2em(-/-) knockout and Mrgprb2em(MRGPRX2) transgenic human MRGPRX2 knock-in mice by assessment of agonist-induced skin vascular permeability. Ex vivo skin mast cell degranulation and associated histamine release was evaluated by microdialysis of human skin tissue samples. RESULTS: MRGPRX2 antagonists potently inhibited agonist-induced MRGPRX2 activation and mast cell degranulation in all mast cell types tested in an IgE-independent manner. Orally administered MRGPRX2 antagonists also inhibited agonist-induced degranulation and resulting vascular permeability in MRGPRX2 knock-in mice. In addition, antagonist treatment dose dependently inhibited agonist-induced degranulation in ex vivo human skin. CONCLUSIONS: MRGPRX2 small molecule antagonists potently inhibited agonist-induced mast cell degranulation in vitro and in vivo as well as ex vivo in human skin, supporting potential therapeutic utility as a novel treatment for multiple human diseases involving clinically relevant mast cell activation.

Psychosocial correlates of parents' willingness to vaccinate their children against COVID-19.

BACKGROUND: Public health guidance recommended that children who are 6 months or older be vaccinated against COVID-19 in June of 2022. In the U.S., 56% of children under 17 had not received the COVID-19 vaccination in 2023. We examine parents' willingness to vaccinate their children against COVID-19 using the theory of planned behavior in order to design effective strategies to promote vaccine uptake. METHODS: The Philadelphia Community Engagement Alliance is part of an NIH community-engaged consortium focused on addressing COVID-19 disparities across the U.S. We surveyed 1,008 Philadelphia parents (mean age 36.86, SD 6.55; 42.3% racial/ethnic minorities) between September 2021 and February 2022, a period when guidance for child vaccination was anticipated. Structural Equation Modeling analysis examined associations between parental willingness and vaccine-related attitudes, norms, and perceived control. Covariates included parents' COVID-19 vaccination status, race/ethnicity, gender, and survey completion post-CDC pediatric COVID-19 vaccination guidelines. Subgroup analyses by race/ethnicity and gender were conducted. RESULTS: Our model demonstrated good fit (χ2 = 907.37, df = 419, p<0.001; comparative fit index [CFI] = 0.951; non-normed fit index [NNFI] = 0.946; root mean square error of approximation [RMSEA] = 0.034 with 95% CI = 0.030-0.038). Attitudes ([Formula: see text] = 0.447, p<0.001) and subjective norms ([Formula: see text] = 0.309, p = 0.002) were predictors of intention. Racial/ethnic minority parents exhibited weaker vaccination intentions ([Formula: see text] = -0.053, p = 0.028) than non-Hispanic White parents. CONCLUSIONS: Parents' attitudes and norms influence their vaccination intentions. Despite the survey predating widespread child vaccine availability, findings are pertinent given the need to increase and sustain pediatric vaccinations against COVID-19. Interventions promoting positive vaccine attitudes and prosocial norms are warranted. Tailored interventions and diverse communication strategies for parental subgroups may be useful to ensure comprehensive and effective vaccination initiatives.

Risk Factors for Progression of Cervical Congenital Scoliosis and Associated Compensatory Curve Behavior.

Background: This study investigated risk factors for progression of deformity in pediatric congenital cervical scoliosis (CCS) and evaluated the correlation between congenital cervical curves and compensatory thoracic and lumbar curves. Methods: Medical records were retrospectively reviewed for 38 pediatric patients with CCS with a minimum 2-year follow-up. Curve progression was defined as >10° increase in cervical coronal curve angle between presentation and last follow-up. Results: A total of 38 patients (16 girls, 22 boys) with a mean age at presentation of 5.6 ± 4.1 years met the inclusion criteria. Sixteen patients (42%) had curve progression with a mean follow-up of 3.1 ± 3.0 years. At presentation, T1 slope was significantly larger among children with progressive deformities (p = 0.041). A total of 18 of the 38 patients with strictly cervical spine deformity were then selected for subanalysis to evaluate the progression of compensatory curves. Cervical major coronal curves were found to significantly correlate with lumbar major coronal curves (r = 0.409), C2 central sacral vertical line (CSVL) (r = 0.407), and C7-CSVL (r = 0.403) (p < 0.05). Thoracic major coronal curves did not significantly correlate with cervical major coronal curves (r = 0.218) (p > 0.05). Conclusion: In conclusion, 42% of osseous CCS curves progressed over time in the overall cohort, and high initial T1 slope was found to be most highly correlated with progression of cervical deformity. Cervical major coronal curves significantly correlated with lumbar curve magnitude but not with thoracic curve size in isolated CCS, possibly due to the increased flexibility of the lumbar spine which may allow greater compensatory balance and thus have a greater correlation with cervical curve magnitude and possibly progression.

The association between street construction projects and community violence in New York City.

Introduction: Community violence is a major cause of injury and death in the United States. Empirical studies have identified that some place-based interventions of urban private places, such as remediations of vacant lots and buildings, are associated with reductions in community violence in surrounding areas. The aim of this study was to examine whether routine maintenance and repair of urban public places (e.g., street construction projects) are also associated with reductions in community violence, proxied by violent crime. Method: This staggered adoption difference-in-difference analysis investigated the association between street construction projects and community violence in New York City from 2010-2019, divided into 40 calendar quarters. The units of analysis were street-quarters (n = 155,280). Intervention street-quarters were those with completed projects in 2010-2019; control streets were those where projects were scheduled but not completed before 2019. The outcome of community violence was proxied by counts of crime and violence incidents reported to the New York Police Department, within street-quarters. Results: There were 79,592 street-quarters with any community violence incidents (51.2%). We found that street construction projects were associated with a decrease in reckless endangerment (ATT = -0.013; 95% CI = -0.021, -0.004), robbery (ATT = -0.035; 95% CI = -0.063, -0.007), and weapons offenses (ATT = -0.016; 95% CI = -0.031, -0.001) occurring on street-quarters. Conclusion: Street construction projects may be yet another type of place-based intervention to reduce community violence.