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Background: The emergence of new skills in the setting of dementia suggests that loss of function in one brain area can release new functions elsewhere.Aims: To characterise 12 patients with frontotemporal dementia (FTD) who acquired, or sustained, new musical or visual abilities despite progression of their dementia.Method: Twelve patients with FTD who acquired or maintained musical or artistic ability were compared with 46 patients with FTD in whom new or sustained ability was absent.Results: The group with musical or visual ability performed better on visual, but worse on verbal tasks than did the other patients with FTD. Nine had asymmetrical left anterior dysfunction. Nine showed the temporal lobe variant of FTD.Conclusion: Loss of function in the left anterior temporal lobe may lead to facilitation of artistic or musical skills. Patients with the left-sided temporal lobe variant of FTD offer an unexpected window into the neurological mediation of visual and musical talents. [ABSTRACT FROM AUTHOR]

Twenty-four patients who developed their first psychotic episode after the age of 45 were studied with MRI and comprehensive neuropsychological testing and compared with 72 healthy elderly subjects. The patients demonstrated more clinical abnormalities on MRI, were more likely to have large white-matter lesions or metabolic illness, and did more poorly on many neuropsychological tests, particularly those testing frontal-lobe and memory abilities. We conclude that structural brain injury is commonly associated with the late onset of psychosis. Neuroimaging investigations are a valuable component in the evaluation of this patient group. [ABSTRACT FROM AUTHOR]

In a prospective study of late-life onset psychosis, five of the first 27 patients studied had extensive white-matter lesions demonstrated by MRI and/or CT. None of 60 age-matched psychiatrically healthy controls demonstrated such lesions. All five patients had a mild dementia and a frontal behavioural syndrome. In addition, every patient performed poorly on neuropsychological tests of frontal function. Dysfunction of the frontal cortex associated with white-matter lesions appears to contribute to the clinical picture of some cases of late-life psychosis. [ABSTRACT FROM AUTHOR]

We apply the color–magnitude intercept calibration method (CMAGIC) to the Nearby Supernova Factory SNe Ia spectrophotometric data set. The currently existing CMAGIC parameters are the slope and intercept of a straight line fit to the linear region in the color–magnitude diagram, which occurs over a span of approximately 30 days after maximum brightness. We define a new parameter, ω XY , the size of the "bump" feature near maximum brightness for arbitrary filters X and Y. We find a significant correlation between the slope of the linear region, β XY , in the CMAGIC diagram and ω XY . These results may be used to our advantage, as they are less affected by extinction than parameters defined as a function of time. Additionally, ω XY is computed independently of templates. We find that current empirical templates are successful at reproducing the features described in this work, particularly SALT3, which correctly exhibits the negative correlation between slope and "bump" size seen in our data. In 1D simulations, we show that the correlation between the size of the "bump" feature and β XY can be understood as a result of chemical mixing due to large-scale Rayleigh–Taylor instabilities. [ABSTRACT FROM AUTHOR]

As a candidate 'super-Chandrasekhar' or 09dc-like Type Ia supernova (SN Ia), SN 2012dn shares many characteristics with other members of this remarkable class of objects but lacks their extraordinary luminosity. Here, we present and discuss the most comprehensive optical data set of this SN to date, comprised of a densely sampled series of early-time spectra obtained within the Nearby Supernova Factory project, plus photometry and spectroscopy obtained at the Very Large Telescope about 1 yr after the explosion. The light curves, colour curves, spectral time series, and ejecta velocities of SN 2012dn are compared with those of other 09dc-like and normal SNe Ia, the overall variety within the class of 09dc-like SNe Ia is discussed, and new criteria for 09dc-likeness are proposed. Particular attention is directed to additional insight that the late-phase data provide. The nebular spectra show forbidden lines of oxygen and calcium, elements that are usually not seen in late-time spectra of SNe Ia, while the ionization state of the emitting iron plasma is low, pointing to low ejecta temperatures and high densities. The optical light curves are characterized by an enhanced fading starting ∼60 d after maximum and very low luminosities in the nebular phase, which is most readily explained by unusually early formation of clumpy dust in the ejecta. Taken together, these effects suggest a strongly perturbed ejecta density profile, which might lend support to the idea that 09dc-like characteristics arise from a brief episode of interaction with a hydrogen-deficient envelope during the first hours or days after the explosion. [ABSTRACT FROM AUTHOR]

Aims. The scientific yield of current and future optical surveys is increasingly limited by systematic uncertainties in the flux calibration. This is the case for type Ia supernova (SN Ia) cosmology programs, where an improved calibration directly translates into improved cosmological constraints. Current methodology rests on models of stars. Here we aim to obtain flux calibration that is traceable to state-of-the-art detector-based calibration. Methods. We present the SNIFS Calibration Apparatus (SCALA), a color (relative) flux calibration system developed for the SuperNova integral field spectrograph (SNIFS), operating at the University of Hawaii 2.2 m (UH 88) telescope. Results. By comparing the color trend of the illumination generated by SCALA during two commissioning runs, and to previous laboratory measurements, we show that we can determine the light emitted by SCALA with a long-term repeatability better than 1%. We describe the calibration procedure necessary to control for system aging. We present measurements of the SNIFS throughput as estimated by SCALA observations. Conclusions. The SCALA calibration unit is now fully deployed at the UH 88 telescope, and with it color-calibration between 4000 Å and 9000 Å is stable at the percent level over a one-year baseline. [ABSTRACT FROM AUTHOR]

Community-clinical partnerships are an effective approach to connecting primary care with public health to increase disease prevention and screenings and reduce health inequities. We explore how the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) award recipients and clinic teams are using community-clinical linkages to deliver services to populations who are without access to health care and identify barriers, facilitators, and lessons that can be used to improve program implementation. We used purposive sampling to select nine state recipients of the NBCCEDP and a clinic partner for each recipient. The data collection was implemented through a multimodal approach using questionnaires, semistructured interviews, and focus groups. Partnerships between award recipients and clinic teams enhanced planning as clinics were able to optimize the use of electronic medical records to identify women who were not up to date with screening. Partnerships with community organizations, hospital systems, and academic institutions were important to increase community outreach and access to services. These partnerships offered a source of client referrals, a forum to deliver in-person education, a platform for joint dissemination activities to reach a wider audience, collaborations to provide transportation, and coverage for clinical services not available at NBCCEDP participating clinics. In conclusion, partnerships between various organizations are important to enhance planning, increase outreach, and improve access to cancer screening. Internal organizational and external support is important to identify appropriate partners, and technical assistance and training may be beneficial to maintain and optimize community partnerships to address health disparities.

Background: Venous thromboembolisms constitute a major cause of morbidity and mortality with 60,000 to 100,000 deaths attributed to pulmonary embolism in the US annually. Both clinical presentations and treatment strategies can vary greatly, and the selection of an appropriate therapeutic strategy is often provider specific. A pulmonary embolism response team (PERT) offers a multidisciplinary approach to clinical decision making and the management of high-risk pulmonary emboli. There is insufficient data on the effect of PERT programs on clinical outcomes. Methods: We searched PubMed, Scopus, Web of Science, and Cochrane to identify PERT studies through March 2024. The primary outcome was all-cause mortality, and the secondary outcomes included the rates of surgical thrombectomy, catheter directed thrombolysis, hospital length of stay (HLOS), and ICU length of stay (ICULOS). We used the Newcastle-Ottawa Scale tool to assess studies' quality. We used random-effects models to compare outcomes between the pooled populations and moderator analysis to identify sources of heterogeneity and perform subgroup analysis. Results: We included 13 observational studies, which comprised a total of 12,586 patients, 7512 (60%) patients were from the pre-PERT period and 5065 (40%) patients were from the PERT period. Twelve studies reported the rate of all-cause mortality for their patient population. Patients in the PERT period were associated with similar odds of all-cause mortality as patients in the pre-PERT period (OR: 1.52; 95% CI: 0.80-2.89; p = 0.20). In the random-effects meta-analysis, there was no significant difference in ICULOS between PERT and pre-PERT patients (difference in means: 0.08; 95% CI: -0.32 to 0.49; p = 0.68). There was no statistically significant difference in HLOS between the two groups (difference in means: -0.82; 95% CI: -2.86 to 1.23; p = 0.43). Conclusions: This meta-analysis demonstrates no significant difference in all studied measures in the pre- and post-PERT time periods, which notably included patient mortality and length of stay. Further study into the details of the PERT system at institutions reporting mortality benefits may reveal practice differences that explain the outcome discrepancy and could help optimize PERT implementation at other institutions.

Abstract: Electroconvulsive therapy (ECT) is an effective treatment for patients with severe psychiatric disorders. Stigma and lack of knowledge surrounding ECT are major obstacles for both patients and their caregivers, who play an important role as shared decision-makers. Insight in caregivers' perspectives on ECT can support the consent process and patient compliance with ECT. We aimed to review perspectives on knowledge, attitudes, and experiences of caregivers of adult and adolescent patients who received ECT. We performed a computerized search (EMBASE, MEDLINE) for articles meeting the following inclusion criteria: (1) qualitative studies, quantitative studies, or quasi-experimental studies that (2) report on caregiver perspectives of patients who received ECT. We conducted our systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method. In total, 29 articles were included. Variation in knowledge about ECT was high among caregivers. Their attitudes were generally positive and most would advise for future ECT if necessary. Psychoeducational tools and ECT experience increased knowledge and attitudes in caregivers. In general, caregivers were satisfied with ECT but wanted more information on risks and side effects before ECT. Caregivers reported more positive attitudes toward and had better experiences with ECT compared with patients. Our systematic review demonstrated moderate knowledge, but overall positive attitudes and experiences on ECT in caregivers. Overall low methodological quality of included studies limits our conclusions. Future research should focus more on qualitative methods and cohort studies., Competing Interests: The authors have no conflicts of interest or financial disclosures to report., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Methods: Our study sought to evaluate if an association exists between Helicobacter pylori (H. pylori), metabolic dysfunction- associated steatotic liver disease (MASLD), and liver fibrosis in patients with severe obesity (BMI > 35). Our retrospective study included 584 patients over the age of 18 years with severe obesity, who underwent preoperative liver transient elastography (VCTE), upper endoscopy, blood work, and intra-operative liver biopsy concurrent with bariatric surgery at a single institution from July 2020 to September 2021. Liver fibrosis scores including FIB-4, APRI, NAFLD fibrosis score, BARD score, AST: ALT ratio, and NAFLD activity score (NAS) were calculated from the laboratory results and liver biopsy findings. The presence or absence of H. pylori was determined based on gastric biopsies obtained during upper endoscopy. Other variables collected included age, gender, mean preoperative weight, BMI, and the presence or absence of comorbidities. Student's t-test and non-parametric testing were used for the analysis of continuous variables and Chi-square analysis was used for categorical data., Results: Of the 584 patients, 14.7% were H. pylori positive and 85.3% were negative. Liver fibrosis scores including FIB-4, APRI, and NAFLD fibrosis scores were significantly higher in the positive group (p < 0.05), but there was no difference in AST: ALT ratio and BARD score. A significantly higher VCTE steatosis and fibrosis scores were noted in the H. pylori-positive group (p < 0.05). Similarly, a significantly higher NAS (NAFLD activity score) on liver biopsies was noted in the positive group, with all the individual components of NAS (steatosis, lobular inflammation, and hepatocyte ballooning) being significantly higher in the positive group (p < 0.05). A significantly higher incidence of fibrosis on liver biopsies was noted in the positive group overall and across all stages of fibrosis (p < 0.05). There were no significant differences between the groups in relation to gender, mean weight, BMI, presence of comorbidities including Diabetes Mellitus, and laboratory values., Conclusion: Our study demonstrates that H. pylori colonization or infection is associated with a higher risk of development of MASLD and progression to fibrosis. Further, population-based studies are needed to corroborate our findings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

More work is needed to establish the validity of the Alternative Model of Personality Disorders (AMPD) in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Acceptance of the AMPD as the primary model of personality disorder requires identifying neurocognitive validators of AMPD-defined personality functioning and demonstrating superiority of the AMPD over the traditional categorical model of personality disorder. It is also important to establish the utility of the AMPD in a developmental context given evidence that personality disorder emerges in adolescence. We assessed the incremental validity of AMPD-defined level of personality functioning (LPF) versus borderline personality features (BPF) in explaining alterations in neural processing of social acceptance feedback in early adolescent girls. One hundred nine girls (M age  = 12.21, SD = 1.21; N = 79 with a psychiatric history) completed a computerized peer interaction task to elicit neural response to social acceptance feedback via electroencephalogram (EEG). Subjects or caregivers reported adolescent psychopathology. In hierarchical regressions controlling for neural response to social rejection and internalizing and externalizing symptoms, LPF incremented BPF and all other covariates in predicting response to social acceptance, but BPF did not. Higher LPF impairment was associated with enhanced reactivity to social acceptance (St.b = 0.274, p = 0.018). LPF appears to provide additional information about neural response to social reward in early adolescence beyond that provided by borderline personality features. These findings add to an emerging literature demonstrating the validity and superiority of the AMPD and help build the rationale for moving toward the AMPD as the primary model of personality disorder classification., (© 2025 The Authors Personality and Mental Health Published by John Wiley & Sons Ltd.)

Objective: In a cohort of patients who were treated with resection and adjuvant radiotherapy (RT) for adamantinomatous craniopharyngioma (ACP), the authors aimed to determine whether gross tumor volume (GTV) at the initiation of RT was associated with the risk of progressive disease (PD) following treatment., Methods: Pediatric and adolescent patients who received surgery and RT for ACP at a single institution from 1998 to 2021 were identified. Univariable Cox regression analyses (UVAs) were performed to assess the association between pre-RT GTV and PD after RT. Multivariable analyses (MVAs) were used to control for potential confounders. Two different endpoints were used to define PD. The first definition was based on radiographic tumor growth, with or without progression of clinical symptoms. The second definition was the requirement for an additional tumor-directed intervention following the completion of RT., Results: Forty-eight patients were eligible for inclusion. The median age at diagnosis was 7.9 years (range 2.1-17.4 years). All patients were treated with surgery and RT with a median dose of 52.2 Gy (range 45-55.8 Gy) and median GTV of 9.86 cm3 (range 0.7-117.7 cm3). After a median follow-up of 66.4 months, 8 patients experienced PD based on both definitions. The 5-year event-free survival rate was 85.4% (95% CI 74.1%-98.3%). On both UVA and MVA, GTV was significantly associated with an increased likelihood of PD (UVA: HR 1.02, 95% CI 1.00-1.04, p = 0.02; MVA: HR 1.10, 95% CI 1.02-1.19, p = 0.01). However, after exclusion of a single outlier with a GTV of 117.7 cm3 prior to RT (remainder of the cohort: range 0.7-37.3 cm3), a second analysis identified no significant association between GTV and PD (UVA: HR 1.03, 95% CI 0.96-1.10, p = 0.4; MVA: HR 1.06, 95% CI 0.96-1.17, p = 0.24)., Conclusions: The authors conclude that for most children and adolescents with ACP, the GTV at the initiation of RT is not associated with the risk of PD. This finding may influence surgical practice, because it suggests that aggressive tumor debulking for the purpose of improving the efficacy of RT may not be necessary. In the case of giant tumors, however, novel strategies may be needed for tumor control.

Significant gains have been made in the treatment of personality disorder among young people. However, effect sizes for evidence-based treatments have been modest, and emerging evidence suggests the potential of generalist approaches to improve outcomes in this population. The aim of this review was to highlight how generalist approaches such as good psychiatric management for adolescents (GPM-A) hold promise for early intervention for personality disorders among young people. The authors discuss recent advances in clinical understanding of the diagnosis and treatment of personality disorder among youths and demonstrate how these advances align with GPM-A. Specifically, the authors show how several of GPM-A's guiding principles-most notably the need for access, common-factor approaches, and a focus on interpersonal hypersensitivity and restoring general functioning-align with these advances. This review suggests that GPM-A provides a timely and promising framework for innovating early interventions for personality disorder among young people., Competing Interests: Dr. Choi-Kain receives royalties from the American Psychiatric Association and Springer, serves as a consultant for Tetricus Labs, and has served as a consultant for Boehringer Ingelheim. Dr. Sharp receives book royalties from the American Psychiatric Association. The other author reports no financial relationships with commercial interests. Holly A. Swartz, M.D., Editor of the journal, was the decision editor during peer review.

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections in the USA and of preventable blindness worldwide. This obligate intracellular pathogen replicates within a membrane-bound inclusion, but how it acquires nutrients from the host while avoiding detection by the innate immune system is incompletely understood. C. trachomatis accomplishes this in part through the translocation of a unique set of effectors into the inclusion membrane, the inc lusion membrane proteins (Incs). Incs are ideally positioned at the host-pathogen interface to reprogram host signaling by redirecting proteins or organelles to the inclusion. Using a combination of co-affinity purification, immunofluorescence confocal imaging, and proteomics, we characterize the interaction between an early-expressed Inc of unknown function, Tri1, and tumor necrosis factor receptor-associated factor 7 (TRAF7). TRAF7 is a multi-domain protein with a RING finger ubiquitin ligase domain and a C-terminal WD40 domain. TRAF7 regulates several innate immune signaling pathways associated with C. trachomatis infection and is mutated in a subset of tumors. We demonstrate that Tri1 and TRAF7 specifically interact during infection and that TRAF7 is recruited to the inclusion. We further show that the predicted coiled-coil domain of Tri1 is necessary to interact with the TRAF7 WD40 domain. Finally, we demonstrate that Tri1 displaces the native TRAF7 binding partners, mitogen-activated protein kinase kinase kinase 2 (MEKK2), and MEKK3. Together, our results suggest that by displacing TRAF7 native binding partners, Tri1 has the capacity to alter TRAF7 signaling during C. trachomatis infection.IMPORTANCE Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections in the USA and preventable blindness worldwide. Although easily treated with antibiotics, the vast majority of infections are asymptomatic and therefore go untreated, leading to infertility and blindness. This obligate intracellular pathogen evades the immune response, which contributes to these outcomes. Here, we characterize the interaction between a C. trachomatis -secreted effector, Tri1, and a host protein involved in innate immune signaling, TRAF7. We identified host proteins that bind to TRAF7 and demonstrated that Tri1 can displace these proteins upon binding to TRAF7. Remarkably, the region of TRAF7 to which these host proteins bind is often mutated in a subset of human tumors. Our work suggests a mechanism by which Tri1 may alter TRAF7 signaling and has implications not only in the pathogenesis of C. trachomatis infections but also in understanding the role of TRAF7 in cancer., Competing Interests: The authors declare no conflict of interest.

Peri-implantitis is a complex infectious disease that manifests as progressive loss of alveolar bone around the dental implants and hyper-inflammation associated with microbial dysbiosis. Using antibiotics in treating peri-implantitis is controversial because of antibiotic resistance threats, the non-selective suppression of pathogens and commensals within the microbial community, and potentially serious systemic sequelae. Therefore, conventional treatment for peri-implantitis comprises mechanical debridement by nonsurgical or surgical approaches with adjunct local microbicidal agents. Consequently, current treatment options may not prevent relapses, as the pathogens either remain unaffected or quickly re-emerge after treatment. Successful mitigation of disease progression in peri-implantitis requires a specific mode of treatment capable of targeting keystone pathogens and restoring bacterial community balance toward commensal species. Antimicrobial peptides (AMPs) hold promise as alternative therapeutics through their bacterial specificity and targeted inhibitory activity. However, peptide sequence space exhibits complex relationships such as sparse vector encoding of sequences, including combinatorial and discrete functions describing peptide antimicrobial activity. In this paper, we generated a transparent Machine Learning (ML) model that identifies sequence-function relationships based on rough set theory using simple summaries of the hydropathic features of AMPs. Comparing the hydropathic features of peptides according to their differential activity for different classes of bacteria empowered predictability of antimicrobial targeting. Enriching the sequence diversity by a genetic algorithm, we generated numerous candidate AMPs designed for selectively targeting pathogens and predicted their activity using classifying rough sets. Empirical growth inhibition data is iteratively fed back into our ML training to generate new peptides, resulting in increasingly more rigorous rules for which peptides match targeted inhibition levels for specific bacterial strains. The subsequent top scoring candidates were empirically tested for their inhibition against keystone and accessory peri-implantitis pathogens as well as an oral commensal bacterium. A novel peptide, VL-13, was confirmed to be selectively active against a keystone pathogen. Considering the continually increasing number of oral implants placed each year and the complexity of the disease progression, prevalence of peri-implant diseases continues to rise. Our approach offers transparent ML-enabled paths towards developing antimicrobial peptide-based therapies targeting the changes in the microbial communities that can beneficially impact disease progression., Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Novel medical technologies are designed to aid in cardiopulmonary resuscitation both in and out of the hospital. Out-of-hospital innovations utilize the skills of paramedics, bystanders, and other prehospital personnel, while in-hospital innovations traditionally aid in physician intervention. Our review of current literature aims to describe the benefits and limitations of six main technologic advancements with wide adoption for their practicality and functionality. The six key technologies include: extracorporeal membrane oxygenation (ECMO), real-time feedback devices, smart devices, video review, point-of-care ultrasound, and unmanned aerial vehicle (drone) automated external defibrillator (AED) delivery. The benefits and limitations of each technology were independently reviewed and expounded upon. Newer technologies like drone AED delivery, paramedic ultrasound use, and smart devices have been demonstrated to be safe and feasible, however, further studies are needed to compellingly demonstrate improved patient outcomes. In-hospital use of ECMO and ultrasound is well established by current literature to aid in cardiopulmonary resuscitation and improve patient outcomes.

The current study investigated the understudied relationship between pubertal timing and borderline personality disorder (BPD) symptoms in males and females. We conducted hierarchical linear regressions in a longitudinal Cohort 1 ( N = 117) and a cross-sectional Cohort 2 ( N = 127). Cohort 1: Pubertal timing was self-reported at age 10; BPD symptoms and covariates were assessed between ages 13 and 19. Cohort 2: All assessments were between ages 8 and 12. Covariates: race, age, internalizing and externalizing symptoms, and income-to-needs ratio. Sex differences were examined post hoc. In Cohort 1, early gonadal timing was associated with more BPD symptoms in females (beta = .46, p = .002), and late gonadal timing was associated with more BPD symptoms in males (beta = -.23, p = .035). In Cohort 2, early gonadal timing was associated with more BPD symptoms (beta = .21, p = .033) without sex moderation. Results indicate that early gonadal development could be a risk indicator for the emergence of BPD in adolescence, particularly in females, which could inform causal mechanisms and intervention targets.

Localization of a variety of RNAs to non-membrane-bound cellular compartments such as nucleoli and Cajal bodies is critical for their stability and function. The molecular mechanisms that underly the recruitment and exclusion of RNAs from these phase-separated organelles is incompletely understood. Telomerase is a ribonucleoprotein composed of the reverse transcriptase protein telomerase reverse transcriptase (TERT), the telomerase RNA (TR), and several auxiliary proteins, including TCAB1. Here we show that in the absence of TCAB1, a large fraction of TR is tightly bound to the nucleolus, while TERT is largely excluded from the nucleolus, reducing telomerase assembly. This suggests that nuclear compartmentalization by the non-membrane-bound nucleolus counteracts telomerase assembly, and TCAB1 is required to retain TR in the nucleoplasm. Our work provides insight into the mechanism and functional consequences of RNA recruitment to organelles formed by phase separation and demonstrates that TCAB1 plays an important role in telomerase assembly., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: COVID-19 vaccines are safe, effective, and widely available, but many adults in the U.S. have not been vaccinated for COVID-19. This study examined the associations between behavioral and social drivers of vaccination with COVID-19 vaccine uptake in the U.S. adults and their prevalence by region., Methods: A nationally representative sample of U.S. adults participated in a cross-sectional telephone survey in August-November 2021; the analysis was conducted in January 2022. Survey questions assessed self-reported COVID-19 vaccine initiation, demographics, and behavioral and social drivers of vaccination., Results: Among the 255,763 respondents, 76% received their first dose of COVID-19 vaccine. Vaccine uptake was higher among respondents aged ≥75 years (94%), females (78%), and Asian non-Hispanic people (94%). The drivers of vaccination most strongly associated with uptake included higher anticipated regret from nonvaccination, risk perception, and confidence in vaccine safety and importance, followed by work- or school-related vaccination requirements, social norms, and provider recommendation (all p<0.05). The direction of association with uptake varied by reported level of difficulty in accessing vaccines. The prevalence of all of these behavioral and social drivers of vaccination was highest in the Northeast region and lowest in the Midwest and South., Conclusions: This nationally representative survey found that COVID-19 vaccine uptake was most strongly associated with greater anticipated regret, risk perception, and confidence in vaccine safety and importance, followed by vaccination requirements and social norms. Interventions that leverage these social and behavioral drivers of vaccination have the potential to increase COVID-19 vaccine uptake and could be considered for other vaccine introductions., (Published by Elsevier Inc.)

Overcoming the short lifespan of current dental adhesives remains a significant clinical need. Adhesives rely on formation of the hybrid layer to adhere to dentin and penetrate within collagen fibrils. However, the ability of adhesives to achieve complete enclosure of demineralized collagen fibrils is recognized as currently unattainable. We developed a peptide-based approach enabling collagen intrafibrillar mineralization and tested our hypothesis on a type-I collagen-based platform. Peptide design incorporated collagen-binding and remineralization-mediating properties using the domain structure conservation approach. The structural changes from representative members of different peptide clusters were generated for each functional domain. Common signatures associated with secondary structure features and the related changes in the functional domain were investigated by attenuated total reflectance Fourier-transform infrared (ATR-FTIR) and circular dichroism (CD) spectroscopy, respectively. Assembly and remineralization properties of the peptides on the collagen platforms were studied using atomic force microscopy (AFM). Mechanical properties of the collagen fibrils remineralized by the peptide assemblies was studied using PeakForce-Quantitative Nanomechanics (PF-QNM)-AFM. The engineered peptide was demonstrated to offer a promising route for collagen intrafibrillar remineralization. This approach offers a collagen platform to develop multifunctional strategies that combine different bioactive peptides, polymerizable peptide monomers, and adhesive formulations as steps towards improving the long-term prospects of composite resins.

Collagen is fundamental to a vast diversity of health functions and potential therapeutics. Short peptides targeting collagen are attractive for designing modular systems for site-specific delivery of bioactive agents. Characterization of peptide-protein binding involves a larger number of potential interactions that require screening methods to target physiological conditions. We build a hydropathy-based free energy estimation tool which allows quick evaluation of peptides binding to collagen. Previous studies showed that pH plays a significant role in collagen structure and stability. Our design tool enables probing peptides for their collagen-binding property across multiple pH conditions. We explored binding features of currently known collagen-binding peptides, collagen type I alpha chain 2 sense peptide (TKKTLRT) and decorin LRR-10 (LRELHLNNN). Based on these analyzes, we engineered a collagen-binding peptide with enhanced properties across a large pH range in contrast to LRR-10 pH dependence. To validate our predictions, we used a quantum-dots-based binding assay to compare the coverage of the peptides on type I collagen. The predicted peptide resulted in improved collagen binding. Hydropathy of the peptide-protein pair is a promising approach to finding compatible pairings with minimal use of computational resources, and our method allows for quick evaluation of peptides for binding to other proteins. Overall, the free-energy-based tool provides an alternative computational screening approach that impacts protein interaction search methods., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Introduction: Little is known about how the drivers of COVID-19 vaccination vary across the U.S. To inform vaccination outreach efforts, this study explores geographic variation in correlates of COVID-19 nonvaccination among adults., Methods: Participants were a nationally representative sample of U.S. adults identified through random-digit dialing for the National Immunization Survey-Adult COVID Module. Analyses examined the geographic and temporal landscape of constructs in the Behavioral and Social Drivers of Vaccination Framework among unvaccinated respondents from May 2021 to December 2021 (n=531,798) and sociodemographic and geographic disparities and Behavioral and Social Drivers of Vaccination predictors of COVID-19 nonvaccination from October 2021 to December 2021 (n=187,756)., Results: National coverage with at least 1 dose of COVID-19 vaccine was 79.3% by December 2021, with substantial geographic heterogeneity. Regions with the largest proportion of unvaccinated persons who would probably get a COVID-19 vaccine or were unsure resided in the Southeast and Midwest (Health and Human Services Regions 4 and 5). Both regions had similar temporal trends regarding concerns about COVID-19 and confidence in vaccine importance, although the Southeast had especially low confidence in vaccine safety in December 2021, lowest in Florida (5.5%) and highest in North Carolina (18.0%). The strongest Behavioral and Social Drivers of Vaccination correlate of not receiving a COVID-19 vaccination was lower confidence in COVID-19 vaccine importance (adjusted prevalence ratio=5.19, 95% CI=4.93, 5.47; strongest in the Northeast, Southwest, and Mountain West and weakest in the Southeast and Midwest). Other Behavioral and Social Drivers of Vaccination correlates also varied by region., Conclusions: Contributors to nonvaccination showed substantial geographic heterogeneity. Strategies to improve COVID-19 vaccination uptake may need to be tailored regionally., (Published by Elsevier Inc.)

Background: Despite a growing literature detailing early childhood risk factors for borderline personality disorder (BPD), few studies have examined moderating factors that might mitigate or exacerbate the effects of those risk factors. The current study examined whether three preschool-age characteristics-impulsivity, emotional lability, and initiative-taking-moderated the relationship between known preschool-age risk factors and adolescent BPD symptoms., Methods: We performed multilevel modeling analyses in a sample (n = 151) from the Preschool Depression Study, a prospective longitudinal study with assessments from preschool through adolescence. Preschool risk factors included adverse childhood experiences, internalizing symptoms, and externalizing symptoms measured with parent clinical interviews. Preschool moderating factors were assessed via parent report and observational coding of temperament and behavior. The Borderline Personality Features Scale for Children measured BPD symptoms in adolescence., Results: We found that observed initiative-taking moderated the relationship between preschool internalizing symptoms and adolescent BPD symptoms (b = 0.57, p = .011) and moderated the relationship between preschool externalizing symptoms and adolescent BPD symptoms (b = 1.42, p = .013). Greater initiative-taking was associated with lower BPD risk for children with high internalizing or externalizing symptoms. Conversely, for children with low internalizing or externalizing symptoms, greater initiative-taking was associated with increased BPD risk., Conclusions: We identify a potential moderating factor in BPD development, offer novel targets for screening and intervention, and provide a framework for using early childhood observational assessments in BPD research. Our findings suggest the need for future research on early moderating factors in BPD development, which could inform early childhood interventions targeting those factors to mitigate the effects of potentially less malleable risk factors., (© 2022. The Author(s).)

Caries is the most ubiquitous infectious disease of mankind, and early childhood caries (ECC) is the most prevalent chronic disease in children worldwide, with the resulting destruction of the teeth recognized as a global health crisis. Recent the United States Food and Drug Administration (FDA) approval for the use of silver diamine fluoride (SDF) in dentistry offers a safe, accessible, and inexpensive approach to arrest caries progression in children with ECC. However, discoloration, i.e., black staining, of demineralized or cavitated surfaces treated with SDF has limited its widespread use. Targeting SDF-treated tooth surfaces, we developed a biohybrid calcium phosphate nanocomposite interface building upon the self-assembly of synthetic biomimetic peptides. Here, an engineered bifunctional peptide composed of a silver binding peptide (AgBP) is covalently joined to an amelogenin derived peptide (ADP). The AgBP provides anchoring to the SDF-treated tooth tissue, while the ADP promotes rapid formation of a calcium phosphate isomorph nanocomposite mimicking the biomineralization function of the amelogenin protein. Our results demonstrate that the bifunctional peptide was effective in remineralizing the biomineral destroyed by caries on the SDF-treated tooth tissues. The proposed engineered peptide approach offers a biomimetic path for remineralization of the SDF-treated tissues producing a calcium phosphate nanocomposite interface competent to be restored using commonly available adhesive dental composites.

Objective: The purpose of the present study was to compare performance on a wide range of PVTs in a neuropsychology clinic sample of African Americans and White Americans to determine if there are differences in mean scores or cut-off failure rates between the two groups, and to identify factors that may account for false positive PVT results in African American patients., Method: African American and White American non-compensation-seeking neuropsychology clinic patients were compared on a wide range of standalone and embedded PVTs: Dot Counting Test, b Test, Warrington Recognition Memory Test, Rey 15-item plus recognition, Rey Word Recognition Test, Digit Span (ACSS, RDS, 3-digit time, 4-digit time), WAIS-III Picture Completion (Most discrepant index), WAIS-III Digit Symbol/Coding (recognition equation), Rey Auditory Verbal Learning Test, Rey Complex figure, WMS-III Logical Memory, Comalli Stroop Test, Trails A, and Wisconsin Card Sorting Test., Results: When groups were equated for age and education, African Americans obtained mean performances significantly worse than White Americans on only four of 25 PVT scores across the 14 different measures (Stroop Word Reading and Color Naming, Trails A, Digit Span 3-digit time); however, FSIQ was also significantly higher in White American patients. When subjects with borderline IQ (FSIQ = 70 to 79) were excluded (resulting in 74 White Americans and 25 African Americans), groups no longer differed in IQ and only continued to differ on a single PVT cutoff (Trails A). Further, specificity rates in African Americans were comparable to those of White Americans with the exception of the b Test, the Dot Counting Test, and Stroop B., Conclusions: PVT performance generally does not differ as a function of Black versus White race once the impact of intellectual level is controlled, and most PVT cutoffs appear appropriate for use in African Americans of low average IQ or higher.

Background: Individual extracts of Garcinia kola and Kigelia africana have been shown to have therapeutic effects against a variety of variables linked to the development of diabetes mellitus. However, there is still a lack of information about the combined effects of these extracts on Insulin and Paraoxonase 1 (PON-1) in Streptozotocin-Nicotinamide-induced type-2 diabetic Wistar rats., Methods: Forty-two young male rats (180-200g) were randomly divided into six groups (n = 7/group). Diabetes was intraperitoneally induced with 110 mg/kg of nicotinamide constituted in distilled water and fifteen minutes later with 65 mg/kg of streptozocin freshly prepared in 0.1M citrate buffer (pH of 4.5) and treated for six weeks as follows: the control rats received either 0.9% normal saline (NS) or 250 mg/kg extract by gavage. The remaining animals were diabetes induced and subsequently treated with either NS, graded doses of the extract (250 mg/kg and 500 mg/kg), or 5 mg/kg Glibenclamide + 100mg/kg Metformin. Gas chromatography-mass spectrometry (GCMS) of the combined extracts was also analyzed to identify the bioactive compounds present in it. Insulin, PON-1 levels, lipid profiles, and atherogenic index were assessed., Results: Our findings show that Insulin and PON-1 levels in the plasma of diabetic rats treated with the combined extracts were significantly increased when compared to the control rats. Moreover, the GCMS of the extract shows the presence of both monounsaturated (oleic acid) and polyunsaturated (linoleic acid) fatty acids., Conclusion: The current findings suggest that the extract may help improve glucose homeostasis and prevent atherosclerosis through the established mechanism of the identified bioactive compounds., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Empirical antimicrobial use is common in hospitalized infants and may contribute to antimicrobial resistance in low- and middle-income countries. In this observational birth cohort study nested in a randomized controlled trial in Dhaka, Bangladesh, inpatient antimicrobial prescription data were extracted from serious adverse event forms completed for hospitalizations of infants (0-12 months of age). The primary outcome was the proportion of inpatient admissions where systemic antimicrobials were prescribed. Infant and hospitalization-related factors associated with antimicrobial prescriptions were determined. Among 1254 infants, there were 448 admissions to 32 facilities from 2014 to 2016. Antimicrobials were prescribed in 73% of admissions with a mean antimicrobial exposure rate of 0.25 antimicrobials per day of admission [95% confidence intervals (95% CIs): 0.24-0.27]. The most common antibiotics were aminoglycosides (29%), penicillins (26%) and third-generation cephalosporins (25%). In all, 58% of antibiotics were classified as 'access', 38% 'watch' and 1% 'reserve' using the World Health Organization (WHO) Essential Medicines List classification. WHO-recommended antimicrobial regimens were used in 68% of neonatal sepsis and 9% of lower respiratory tract infection (LRTI) admissions. 'Watch' antimicrobials were used in 26% of neonatal sepsis and 76% of LRTI admissions. Compared with private facilities, antimicrobial prescription rates were lower at government [rate ratio (RR) 0.71; 95% CI: 0.61-0.83] and charitable facilities (RR 0.39; 95% CI: 0.28-0.53), after adjustment for household wealth index and parental education. Younger infant age, older maternal age and longer admission were associated with higher prescription rates. These findings highlight the need for paediatric antimicrobial stewardship programs in Bangladesh., (© The Author(s) [2020]. Published by Oxford University Press.)

Resin-based composite materials have been widely used in restorative dental materials due to their aesthetic, mechanical, and physical properties. However, they still encounter clinical shortcomings mainly due to recurrent decay that develops at the composite-tooth interface. The low-viscosity adhesive that bonds the composite to the tooth is intended to seal this interface, but the adhesive seal is inherently defective and readily damaged by acids, enzymes, and oral fluids. Bacteria infiltrate the resulting gaps at the composite-tooth interface and bacterial by-products demineralize the tooth and erode the adhesive. These activities lead to wider and deeper gaps that provide an ideal environment for bacteria to proliferate. This complex degradation process mediated by several biological and environmental factors damages the tooth, destroys the adhesive seal, and ultimately, leads to failure of the composite restoration. This paper describes a co-tethered dual peptide-polymer system to address composite-tooth interface vulnerability. The adhesive system incorporates an antimicrobial peptide to inhibit bacterial attack and a hydroxyapatite-binding peptide to promote remineralization of damaged tooth structure. A designer spacer sequence was incorporated into each peptide sequence to not only provide a conjugation site for methacrylate (MA) monomer but also to retain active peptide conformations and enhance the display of the peptides in the material. The resulting MA-antimicrobial peptides and MA-remineralization peptides were copolymerized into dental adhesives formulations. The results on the adhesive system composed of co-tethered peptides demonstrated both strong metabolic inhibition of S. mutans and localized calcium phosphate remineralization. Overall, the result offers a reconfigurable and tunable peptide-polymer hybrid system as next-generation adhesives to address composite-tooth interface vulnerability.