Preoperative Imaging in Cochlear Implants.

OBJECTIVE: To determine the utility of computed tomography (CT) and magnetic resonance imaging (MRI) in cochlear implant candidates. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral hospital. PATIENTS: A total of 207 cochlear implanted patients with CT and/or MRI. INTERVENTIONS: N/A. MAIN OUTCOME MEASURES: Age versus abnormal radiologic findings, imaging abnormality versus postoperative outcomes, postoperative outcomes versus electrode design, Cambridge Cochlear Implant Protocol (CCIP) status for imaging abnormalities, sensitivity and specificity of CT and MRI for round-window/cochlear occlusion, and MRI for incomplete partitions. RESULTS: A total of 207 patients with CT, MRI, or both were reviewed retrospectively. Less than half (15.5%) of CT scans had findings that might affect surgical intervention compared with 5.9% of MRI. No significant difference was found between children and adults for relevant imaging abnormalities (grade 4 or higher) with either CT (p = 0.931) or MRI (p = 0.606). CCIP status correlated with cochlear abnormalities (p = 0.040); however, only 46.2% of radiographic abnormalities on CT would be identified by these criteria. For detecting cochlear occlusion requiring surgical intervention, the sensitivity and specificity for CT were 40% (4 of 10; 95% confidence interval [CI], 12.16-73.76) and 95.73% (95% CI, 91.40-98.27), respectively. For MRI, the sensitivity and specificity were 33.33% (1 of 3; 95% CI, 0.84-90.57) and 96.97% (63 of 65; 95% CI, 89.32-99.63), respectively. There was no difference for postoperative AzBio scores for higher-grade imaging abnormalities (p = 0.6012) or for electrode designs (p = 0.3699). CONCLUSIONS: Significant radiographic abnormalities were relatively uncommon in cochlear implant patients on either CT or MRI at our single-center institution. If present, abnormal imaging findings rarely translated to management changes. CCIP status does not reliably predict which patients are likely to have abnormalities. Both MRI and CT have low sensitivity for round-window or cochlear occlusion, but detection likely leads to changes in surgical management.

Interim report of the reactogenicity and immunogenicity of SARS-CoV-2 XBB-containing vaccines.

BACKGROUND: Monovalent Omicron XBB.1.5-containing vaccines were approved for Coronavirus disease 2019 (COVID-19) 2023-2024 immunizations. METHODS: This ongoing, open-label, phase 2/3 study evaluated mRNA-1273.815-monovalent (50-µg Omicron XBB.1.5-spike mRNA) and mRNA-1273.231-bivalent (25-µg each Omicron XBB.1.5- and BA.4/BA.5-spike mRNAs))vaccines, administered as 5th doses to adults who previously received a primary series, a 3rd dose of an original mRNA COVID-19 vaccine, and a 4th dose of an Omicron BA.4/BA.5 bivalent vaccine. Interim safety and immunogenicity results 29 days post-vaccination are reported. RESULTS: Participants (randomized 1:1) received 50-µg mRNA-1273.815(n=50) or mRNA-1273.231(n=51); median (interquartile range) months from the prior BA.4/BA.5-bivalent dose were 8.2 (8.1-8.3) and 8.3 (8.1-8.4), respectively. Neutralizing antibody (nAb) increased from pre-booster levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants tested. Day 29 nAb fold-increases from pre-booster levels were numerically higher against XBB.1.5, XBB.1.16, EG.5.1, BA.2.86, and JN.1 than BA.4/BA.5, BQ.1.1 and D614G. The monovalent vaccine also cross-neutralized FL.1.5.1, EG.5.1, BA.2.86, HK.3.1, HV.1 and JN.1 variants in a participant (n=20) subset, 15 days post-vaccination. Reactogenicity was similar to previously reported mRNA-1273 original and bivalent vaccines. CONCLUSIONS: XBB.1.5-containing mRNA-1273 vaccines elicit robust, diverse nAb responses against more recent SARS-CoV-2 variants including JN.1, supporting the XBB.1.5-spike sequence selection for the 2023-2024 COVID-19 vaccine update.

The role of constraints and information gaps in driving risky medicine purchasing practices in four African countries.

Substandard and falsified (SF) medical products pose a major threat to public health and socioeconomic development, particularly in low- and middle-income countries. In response, public education campaigns have been developed to alert consumers about the risks of SF medicines and provide guidance on 'safer' practices, along with other demand- and supply-side measures. However, little is currently known about the potential effectiveness of such campaigns while structural constraints to accessing quality-assured medicines persist. This paper analyses survey data on medicine purchasing practices, information and constraints from four African countries (Ghana, Nigeria, Sierra Leone and Uganda; n > 1000 per country). Using multivariate regression and structural equation modelling, we present what we believe to be the first attempt to tease apart, statistically, the effects of an information gap vs structural constraints in driving potential public exposure to SF medicines. The analysis confirms that less privileged groups (including, variously, those in rural settlements, with low levels of formal education, not in paid employment, often women and households with a disability or long-term sickness) are disproportionately potentially exposed to SF medicines; these same demographic groups also tend to have lower levels of awareness and experience greater levels of constraint. Despite the constraints, our models suggest that public health education may have an important role to play in modifying some (but not all) risky practices. Appropriately targeted public messaging can thus be a useful part of the toolbox in the fight against SF medicines, but it can only work effectively in combination with wider-reaching reforms to address higher-level vulnerabilities in pharmaceutical supply chains in Africa and expand access to quality-assured public-sector health services.

Circulating extracellular choline acetyltransferase regulates inflammation.

BACKGROUND: Choline acetyltransferase (ChAT) is required for the biosynthesis of acetylcholine, the molecular mediator that inhibits cytokine production in the cholinergic anti-inflammatory pathway of the vagus nerve inflammatory reflex. Abundant work has established the biology of cytoplasmic ChAT in neurons, but much less is known about the potential presence and function of ChAT in the extracellular milieu. OBJECTIVES: We evaluated the hypothesis that extracellular ChAT activity responds to inflammation and serves to inhibit cytokine release and attenuate inflammation. METHODS: After developing novel methods for quantification of ChAT activity in plasma, we determined whether ChAT activity changes in response to inflammatory challenges. RESULTS: Active ChAT circulates within the plasma compartment of mice and responds to immunological perturbations. Following the administration of bacterial endotoxin, plasma ChAT activity increases for 12-48 h, a time period that coincides with declining tumor necrosis factor (TNF) levels. Further, a direct activation of the cholinergic anti-inflammatory pathway by vagus nerve stimulation significantly increases plasma ChAT activity, whereas the administration of bioactive recombinant ChAT (r-ChAT) inhibits endotoxin-stimulated TNF production and anti-ChAT antibodies exacerbate endotoxin-induced TNF levels, results of which suggest that ChAT activity regulates endogenous TNF production. Administration of r-ChAT significantly attenuates pro-inflammatory cytokine production and disease activity in the dextran sodium sulfate preclinical model of inflammatory bowel disease. Finally, plasma ChAT levels are also elevated in humans with sepsis, with the highest levels observed in a patient who succumbed to infection. CONCLUSION: As a group, these results support further investigation of ChAT as a counter-regulator of inflammation and potential therapeutic agent.

Reducing the Burden of Disease Associated With Periprosthetic Fractures: Prevention and the Need for Improved Perioperative Care.

The management of periprosthetic fractures remains challenging and controversial. There continues to be a significant burden of disease and substantial resource implications associated with fractures following total joint arthroplasty. Achieving consensus opinions regarding the prevention and treatment of this problem has important implications given the profound effect on patient outcomes. Multidisciplinary care in the preoperative and postoperative settings is critical, with a specific focus on bone health.

American local government elections database.

The study of urban and local politics in the United States has long been hindered by a lack of centralized sources of election data. We introduce a new database of about 78,000 candidates in 57,000 electoral contests that encompasses races for seven distinct local political offices in most medium and large cities and counties in the U.S. over the last three decades. This is the most comprehensive publicly-available source of information on local elections across the country. We provide partisan and demographic information about candidates in these races as well as electoral outcomes. This new database will facilitate a myriad of new research on representation and elections in local governments.

Domain-based mRNA vaccines encoding spike protein N-terminal and receptor binding domains confer protection against SARS-CoV-2.

With the success of messenger RNA (mRNA) vaccines against coronavirus disease 2019, strategies can now focus on improving vaccine potency, breadth, and stability. We designed and evaluated domain-based mRNA vaccines encoding the wild-type spike protein receptor binding domain (RBD) or N-terminal domain (NTD) alone or in combination. An NTD-RBD-linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2° to 8°C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In BALB/c mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses from viral challenge were observed against wild-type, beta, delta, or omicron (BA.1) viruses compared with mRNA-1273-immunized mice, especially at lower vaccine dosages. K18-hACE2 mice immunized with mRNA-1283 or mRNA-1273 as a primary series demonstrated similar degrees of protection from challenge with SARS-CoV-2 Delta and Omicron variants at all vaccine dosages. These results support clinical assessment of mRNA-1283, which has now entered clinical trials (NCT05137236).

Lowering the Incidence of Endophthalmitis Following Intravitreal Anti-VEGF Injection: An Analysis of Aseptic Protocol Adjustment.

BACKGROUND AND OBJECTIVE: The impact of anti-sepsis-anesthesia sequence in intravitreal injection (IVI)-associated endophthalmitis is unknown. We compared outcomes of patients who had 10% topical povidone-iodine before or after 2% topical lidocaine gel during IVIs. PATIENTS AND METHODS: A retrospective study of IVIs in nine clinical sites was undertaken. Group 1 had lidocaine gel applied first. This protocol was changed on March 1, 2020, with Group 2 having povidone-iodine applied first. Visual and micro-biological outcomes were compared. RESULTS: Among 72 cases (0.07%) from 102,908 IVIs, Group 1 had 59 cases from 65,307 IVI (0.09%) and Group 2 had 13 cases from 37,601 IVI (0.03%; P = 0.001). There was no significant difference in the best-corrected visual acuity between groups. Highly virulent bacteria were predominantly isolated in Group 1, but proportions of gram-positive bacterial growth were similar. CONCLUSIONS: Application of povidone-iodine before lidocaine gel, compared to after, significantly decreased rate of IVI endophthalmitis, with no significant changes in visual and microbiological outcomes. [Ophthalmic Surg Lasers Imaging Retina 2023;54:520-525.].

Can a Smartphone Application Help Address Barriers to Reporting Substandard/Falsified Medical Products? A Pilot Study in Tanzania and Indonesia.

INTRODUCTION: Reporting is an essential component of efforts to combat the distribution and circulation of substandard and falsified (SF) medical products worldwide. However, little is known about why health care professionals (HCPs) do not report suspect products to the national medicine regulatory authority (NMRA) and what measures might address this. This pilot study aimed to assess the utility of a smartphone application for reporting SF medical products in Tanzania and Indonesia. METHODS: At baseline, in 2017, HCPs completed a survey describing perceived barriers to reporting and received training in the identification of SF products and received use of the smartphone reporting application (N=309). The application reporting system was piloted for 6 months. Evaluations took place with HCPs and NMRA staff at the midpoint and endline of the pilot study (2018). RESULTS: At baseline, HCPs surveyed (n=254) identified the following key barriers to reporting: difficulties identifying SF products, frustrations with existing reporting systems, and fears that reporting may have personal or reputational repercussions. During the pilot period, HCPs submitted a total of 36 reports of 27 products to the NMRAs in their respective countries; of these, 8 products were determined to be SF and 2 were unregistered. In all 10 cases, appropriate regulatory action was taken. Feedback from HCPs and NMRA staff was positive in both countries, suggesting that the application addressed several barriers to reporting as it was convenient and, importantly, opened a line of communication between HCPs and the NMRA. However, the application did not address all barriers to reporting, such as concerns of repercussions. CONCLUSION: The findings suggest that this smartphone application may be useful for improving HCPs' reporting of suspected SF products. Developing and piloting similar reporting applications in other countries and contexts is required.

Childhood asthma in the Bronx, NY; the impact of pollutants on length of hospital stay.

OBJECTIVE: The length of hospital stay (LOS) is a proxy of asthma exacerbation severity and healthcare cost. The study aims to estimate the effect of ambient air pollution on pediatric asthma LOS in the Bronx, NY. METHODS: A total of 1,920 children admitted to the hospital in Bronx, NY due to asthma during 2017-2019 period were included in the study. Demographic and clinical parameters were obtained from medical records. Daily ozone (O3) and fine particulate matter (PM2.5) measurements were obtained from local air quality networks. Poisson regression adjusting for gender, age, weight status, respiratory infections including influenza, and ambient temperature was applied to determine whether there was an association of air pollution with length of hospital stay. RESULTS: The mean LOS varied by age, sex, weight status, influenza vaccination status, respiratory viral panel (RVP) results, asthma controller use, and asthma classification. After controlling for these factors in Poisson regression, the mean LOS increased up to 10.62% (95%CI: 0.78-21.41; p = 0.03) for an increase of 10 µg/m3 of PM2.5 exposure on admission day, and 3.90% (95%CI = 0.06-7.88; p = 0.05) for an increase of 10 ppbv of O3 concentration during the previous day. CONCLUSION: Ambient particulate and ozone pollution is associated with lengthier hospital stays for pediatric asthma, potentially indicating more severe asthma exacerbations.

Susceptibilidad in vitro a antifúngicos de especies de Cándida / In vitro antifungal susceptibility of Candida spp

Resumen Objetivo. Analizar la susceptibilidad in vitro de aislamientos de Candida spp. provenientes de onicomicosis obtenidos entre 2016 y 2019, para contribuir con el conocimiento sobre la necesidad o no de realizar pruebas de susceptibilidad a los microorganismos aislados antes de prescribir el tratamiento. Métodos. El estudio consistió en identificar 23 aislamientos de Candida spp. utilizando el sistema automatizado Vitek2® (bioMérieux, Francia). Se determinó la susceptibilidad in vitro de estos aislamientos ante dos antifúngicos tópicos (amorolfina y ciclopirox) y dos antifúngicos sistémicos (fluconazol e itraconazol) por el método de microdilución en caldo M27-A3 del Instituto Estándares para el Laboratorio Clínico (CLSI por sus siglas en inglés) de los Estados Unidos de América. Resultados. La mayoría de los aislamientos correspondieron a Candida parapsilosis (34,8 %), seguido por C. albicans (30,3 %), C. guilliermondii (17,4 %), C. tropicalis (8,7 %), C. dubliniensis (4,4 %) y C. krusei (4,4 %). No se encontraron diferencias estadísticamente significativas entre las CIMs de los diferentes antifúngicos y en promedio hubo susceptibilidad para todos los antifúngicos analizados. Sin embargo, para fluconazol se encontró un aislamiento con CIM alta de C. guilliermondii y un aislamiento resistente de C. parapsilosis. Conclusiones. Las directrices internacionales recomiendan pruebas de susceptibilidad para Candida spp. de hemocultivos o tejidos tras infecciones sistémicas. En todas las demás candidiasis se identifica la especie y se revisan sus patrones de susceptibilidad en la literatura. Por lo tanto, es de importancia conocer que aislamientos de onicomicosis de Candida no-albicans, especialmente de C. guilliermondii y C. parapsilosis, presentan una susceptibilidad disminuida a ciertos antifúngicos que se utilizan como tratamiento, por lo que se recomienda realizar pruebas de susceptibilidad en caso de no tener una buena respuesta al tratamiento en casos de onicomicosis por estas levaduras.

Abstract Aim. The purpose of this investigation was to determine the in vitro susceptibility patterns of Candida spp. isolated from onychomycosis, in order to contribute with strategies for optimal clinical laboratory management of patients with onychomycosis infected with these yeasts. Methods . A total of 23 isolates of Candida spp. were identified with the automatized system Vitek®2 (system bioMérieux, France). In vitro susceptibility patterns were evaluated with two topic antifungals (amorolfine and ciclopirox) and two systemic antifungals (fluconazole and itraconazole) using the Clinical Laboratory and Standards Institute (CLSI) broth microdilution M27-A3 guidelines. Results . Most of the isolates were identified as Candida parapsilosis (34,8 %), followed by C. albicans (30,3 %), C. guilliermondii (17,4 %), C. tropicalis (8,7 %), C. dubliniensis (4,4 %) and C. krusei (4,4 %). There were no statistically significant differences among the MICs of the antifungals tested. However, there was one isolate of C. guilliermondii with high MIC for fluconazole and one fluconazole resistant isolate of C. parapsilosis. Conclusions. Susceptibility tests are only recommended internationally for Candida spp. isolated from blood stream or tissue in systemic infections. In every other candidiasis there is only a species identification, while its susceptibility pattern for treatment is reviewed in literature. Therefore, it is important to report that Candida no-albicans isolates from onychomycosis, especially C. guilliermondii and C. parapsilosis, have a reduced susceptibility to some antifungals commonly used for treatment. According to the obtained in vitro results, we recommend performing antifungal susceptibility testing in those cases of onychomycosis caused by Candida spp. no responsive to treatment.

Bilobed flap reconstruction after en-bloc removal of solitary fibrous tumor of the lacrimal sac.

Purpose: To report a rare case of a solitary fibrous tumor (SFT) of the lacrimal sac and discuss considerations for management of similar cases. Observations: We present the case of a 41-year-old woman who presented with a primary lacrimal sac SFT for which she underwent en-bloc surgical resection. We discuss management options for SFTs and our surgical approach for this case: bilobed flap reconstruction of the medial canthus and inferior orbit. Conclusions: We present an uncommon presentation of a rare tumor and a successful one-stage reconstruction with a bilobed flap.

Validation and adaption of an Information-Motivation-Behavioral Skills model of medication adherence in older patients with multimorbidity.

OBJECTIVE: To test and adapt the Information-Motivation-Behavioral Skills (IMB) model in explaining medication adherence for older patients with multimorbidity. METHODS: Older patients with at least three chronic conditions (N = 254) were recruited from community health centers in Changsha, China. All participants completed a self-administrated questionnaire assessing adherence information, personal motivation, social motivation, behavioral skills, medication adherence, depressive symptoms, medication treatment satisfaction, treatment burden, and disease burden. Structural equation modeling was used to examine the hypothesized models and relationships between variables. RESULTS: The final extended IMB model could explain 52.0% of the variance in adherence. Personal motivation (ß = 0.29, p < 0.001), behavioral skills (ß = 0.36, p < 0.001), and medication treatment satisfaction (ß = 0.23, p = 0.001) had a positive direct effect on adherence. Information, social motivation, personal motivation, medication treatment satisfaction, and treatment burden could also affect adherence indirectly through multiple pathways. CONCLUSION: This study demonstrated that an extended IMB model could be used to conceptualize determinants of medication adherence among older patients with multimorbidity. PRACTICAL IMPLICATIONS: Adherence improvement programs might be more effective if targeting psychosocial factors, including adherence information, motivation, behavioral skills, treatment burden, and medication treatment satisfaction.

Developing a Medication Self-Management Program to Enhance Medication Adherence Among Older Adults With Multimorbidity Using Intervention Mapping.

BACKGROUND AND OBJECTIVES: Suboptimal medication adherence is prevalent in older adults with multimorbidity. However, intervention programs for enhancing adherence in this population are limited. This study describes the development process of a medication self-management program for older adults with multimorbidity. RESEARCH DESIGN AND METHODS: We adopted the first 4 steps of the intervention mapping to develop the program: (1) needs assessment, including a literature review, a systematic review, and a cross-sectional study; (2) development of program outcomes and objectives; (3) selection of theory-based intervention methods and practical applications; and (4) development of the program. RESULTS: We conducted a needs assessment to identify factors affecting medication adherence among older adults with multimorbidity and created a logic model of the adherence problem in Step 1. In Step 2, we developed the specific program outcomes and objectives and then selected adherence information, personal motivation, social motivation, behavioral skills, and treatment experiences as modifiable and important targets that needed to change in this program. In Step 3, we chose several theory-based methods and strategies for practical applications. We finally created a nurse-led medication self-management program in Step 4. Feedback from relevant stakeholders refined the intervention protocol and materials. DISCUSSION AND IMPLICATIONS: The newly developed medication self-management program incorporated theory and evidence from literature and empirical studies with the engagement of multiple stakeholders, making it a contextually and culturally appropriate intervention. This study provides insights into strategies for geriatrics health care professionals to support medication self-management among older adults with multimorbidity.

Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant in mice.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in the Omicron lineage has resulted in diminished Coronavirus Disease 2019 (COVID-19) vaccine efficacy and persistent transmission. In this study, we evaluated the immunogenicity and protective efficacy of two, recently authorized, bivalent COVID-19 vaccines that contain two mRNAs encoding Wuhan-1 and either BA.1 (mRNA-1273.214) or BA.4/5 (mRNA-1273.222) spike proteins. As a primary two-dose immunization series in mice, both bivalent vaccines induced greater neutralizing antibody responses against Omicron variants than the parental, monovalent mRNA-1273 vaccine. When administered to mice as a booster at 7 months after the primary vaccination series with mRNA-1273, the bivalent vaccines induced broadly neutralizing antibody responses. Whereas most anti-Omicron receptor binding domain antibodies in serum induced by mRNA-1273, mRNA-1273.214 and mRNA-1273.222 boosters cross-reacted with the antecedent Wuhan-1 spike antigen, the mRNA-1273.214 and mRNA-1273.222 bivalent vaccine boosters also induced unique BA.1-specific and BA.4/5-specific responses, respectively. Although boosting with parental or bivalent mRNA vaccines substantially improved protection against BA.5 compared to mice receiving two vaccine doses, the levels of infection, inflammation and pathology in the lung were lowest in animals administered the bivalent mRNA vaccines. Thus, boosting with bivalent Omicron-based mRNA-1273.214 or mRNA-1273.222 vaccines enhances immunogenicity and confers protection in mice against a currently circulating SARS-CoV-2 strain.

Incidence of neonatal sepsis after universal antenatal culture-based screening of group B streptococcus and intrapartum antibiotics: A multicentre retrospective cohort study.

OBJECTIVE: To compare the incidences of early and late-onset neonatal sepsis, including group B streptococcus (GBS) and Escherichia coli (E. coli) before and after implementation of universal screening and intrapartum antibiotics prophylaxis (IAP). DESIGN: Retrospective cohort study. SETTING: Eight public hospitals and 31 Maternal and Child Health Centres (in Hong Kong. POPULATION: 460 552 women attending routine antenatal service from 2009 to 2020. METHODS: Universal culture-based GBS screening has been offered to eligible women since 2012. Total births, GBS screening tests, maternal GBS colonisation and neonatal sepsis with positive blood or cerebrospinal fluid were retrieved from clinical and laboratory database. MAIN OUTCOME MEASURES: Maternal GBS colonisation rate, early- and late-onset neonatal sepsis (including GBS and E. coli). RESULTS: Of 318 740 women with universal culture-based screening, 63 767 women (20.0%) screened positive. After implementation of GBS screening and IAP, the incidence of early-onset neonatal sepsis decreased (3.25 versus 2.26 per 1000 live births, p < 0.05), including those caused by GBS (1.03 versus 0.26 per 1000 live births, p < 0.05). Segmented regression showed that change in early-onse GBS sepsis incidence after screening was the only significant variable in the outcome trend. There was no significant evidence of increase in incidence of late-onset neonatal sepsis including those caused by GBS. CONCLUSIONS: Universal culture-based GBS screening and IAP were associated with reduction in early-onset neonatal sepsis including GBS disease. Although an increase in incidence of late-onset neonatal sepsis including those caused by GBS cannot be totally ruled out, we did not identify significant evidence that this occurred.

Methodology of the INVestigating traIning assoCiated blasT pAthology (INVICTA) study.

BACKGROUND: Subconcussive blast exposure during military training has been the subject of both anecdotal concerns and reports in the medical literature, but prior studies have often been small and have used inconsistent methods. METHODS: This paper presents the methodology employed in INVestigating traIning assoCiated blasT pAthology (INVICTA) to assess a wide range of aspects of brain function, including immediate and delayed recall, gait and balance, audiologic and oculomotor function, cerebral blood flow, brain electrical activity and neuroimaging and blood biomarkers. RESULTS: A number of the methods employed in INVICTA are relatively easy to reproducibly utilize, and can be completed efficiently, while other measures require greater technical expertise, take longer to complete, or may have logistical challenges. CONCLUSIONS: This presentation of methods used to assess the impact of blast exposure on the brain is intended to facilitate greater uniformity of data collection in this setting, which would enable comparison between different types of blast exposure and environmental circumstances, as well as to facilitate meta-analyses and syntheses across studies.

Development of SARS-CoV-2 mRNA vaccines encoding spike N-terminal and receptor binding domains.

With the success of mRNA vaccines against coronavirus disease 2019 (COVID-19), strategies can now focus on improving vaccine potency, breadth, and stability. We present the design and preclinical evaluation of domain-based mRNA vaccines encoding the wild-type spike-protein receptor-binding (RBD) and/or N-terminal domains (NTD). An NTD-RBD linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2-8°C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses and protection from viral challenge were observed against wild-type, beta, delta, or omicron (BA. 1) compared with mRNA-1273 immunized mice, especially at lower vaccine dosages. These results support clinical assessment of mRNA-1283 ( NCT05137236 ). One Sentence Summary: A domain-based mRNA vaccine, mRNA-1283, is immunogenic and protective against SARS-CoV-2 and emerging variants in mice.

Associations of Pediatric Symptom Checklist Scores with Sexual Activity and Sexually Transmitted Infections in Urban Adolescents.

OBJECTIVE: To assess the association between the Youth Pediatric Symptom Checklist-17 (YPSC-17) and adolescents' reports of ever having sex and with having positive testing results for sexually transmitted infections (STIs). METHODS: Analyzed electronic data from primary care clinics for 27,901 adolescents aged 13-17 years with responses to the YPSC-17 and urine screen results for gonorrhea/chlamydia. RESULTS: On the YPSC-17 in total 8.3% screened positive. Over one quarter (26%) reported ever having sex and 11% of sexually active youth had a positive STI test. Logistic regression analyses revealed increased odds of sexual activity among those positive on the YPSC-17 total (aOR 1.87, 95% CI 1.68-2.08) or any subscale (INT-aOR 1.43, 95% CI 1.32-1.55; EXT-aOR 1.62, 95% CI 1.40-1.88; ATT-aOR 1.67, 95% CI 1.47-1.90). In addition, sexually active youth with positive EXT (aOR 1.41 95% CI 1.00-1.98) scores were more likely to have STIs. CONCLUSION: The YPSC-17 can identify adolescents with heightened risks for STIs.