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Ozge Erdogan,1,2 Sharon M Casey,1,2 Nikita B Ruparel,3 Asgeir Sigurdsson1 1Department of Endodontics, New York University College of Dentistry, New York, NY, USA; 2Department of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine, Boston, MA, USA; 3Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USACorrespondence: Ozge ErdoganDepartment of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine, 188 Longwood Ave, Boston, MA, 02115, USA, Email ozge_erdogan@hsdm.harvard.eduIntroduction and Objectives: Local anesthesia is essential in dentistry in providing intraoperative analgesia and anesthesia. However, knowledge related to its use for management of post-operative pain is limited. Perioperative pain management is especially important for root canal treatment (ie, endodontic therapy), performed by endodontists. In this study, we sought to better understand endodontists’ attitudes regarding the use of long-lasting anesthetic, namely 0.5% bupivacaine HCl with 1:200,000 epinephrine, for the management of post-endodontic pain. Additionally, we aimed to understand the perspectives of dental patients about receiving longer lasting anesthesia for endodontic therapy and to determine factors that affect their anesthetic preferences within the orofacial region.Methods: An email invitation to participate in an anonymous online survey was sent to members of the American Association of Endodontists. Also, 82 patients attending an in-person visit to an endodontic clinic were recruited to the study.Results: Data from 474 endodontic practitioners and 82 patients included in analysis. Among practitioners, the majority reported to either never (33.31%) or rarely (34.84%) using bupivacaine. Most chose “I don’t think I need it” (47%) and “patient discomfort because of longer duration of soft tissue anesthesia” (30.81%) as reasons for not preferring the use of bupivacaine. Of the practitioners who reported at least rare use, most chose bupivacaine for post-operative pain management (78.02%). Conversely, 52% of patients reported that they were likely/most likely to request long-lasting anesthetics for post-operative pain control.Conclusion: Bupivacaine is rarely used as a post-operative pain management strategy for endodontic therapy. Specifically, bupivacaine is not preferred not because of adverse events, toxicity, or slow onset concerns, but rather, because of longer duration of soft tissue anesthesia. However, our data suggest that patients may be willing to receive long-lasting anesthesia. Further patient-centered research should investigate the use of long-lasting anesthetic agents for management of post-endodontic pain.Keywords: bupivacaine, long lasting local anesthesia, post-operative pain, root canal treatment, endodontics

Abstract Microplastics and nanoplastics (collectively, MNPs) are increasingly entering soils, with potential adverse impacts to agriculture and groundwater. Environmental detection, characterization, and quantification of MNPs is difficult and subject to artifacts, often requiring labor-intensive separation from environmental matrices. These analytical challenges make it difficult to conduct experiments investigating specific MNP characteristics influencing their transport and fate, particularly when examining multiple plastic types at low concentrations. By synthesizing a suite of metal-tagged polymers, which are cryomilled to create polydisperse fragmented particle suspensions, single particle ICP-MS (spICP-MS) can be used to quantify MNP particle size and concentration in controlled fate and transport studies. Use of unique metal-polymer pairs enables accurate, simultaneous analysis of multiple MNP types which can be used to track total particle transport and retention within a variety of environmental matrices. This was demonstrated using saturated sand column transport experiments to quantify the movement of two plastics having different properties: tin-tagged polystyrene (Sn-PS) and tantalum-tagged polyvinylpyrrolidone (Ta-PVP). The behavior of these polydisperse, fragmented MNPs was compared to that of fluorescent, carboxylated monodisperse PS spherical microspheres (Fl-PS). Mobility of all MNP types increased with decreasing particle size, and hydrophilic Ta-PVP particles migrated more effectively than the hydrophobic Sn-PS particles. Furthermore, the addition of humic acid (HA) to the carrier solution increased the colloidal stability of both metal-tagged MNP suspensions, resulting in much greater elution from the column than in HA-free deionized water or moderately- hard water (ionic strength = 5mM). This combination of particle synthesis and spICP-MS analysis provides insights into the transport of MNP having physical properties that are representative of environmental MNPs and opens up a broad range of applications for study of MNP environmental fate and transport.

Introduction: Community paramedicine is a field in its infancy. The use of community paramedics has expanded in recent years as an alternative or adjunct to home health in the continued drive to decrease health disparities and complications. In current practice, they function in a position like a home healthcare nurse with an expanded scope of practice, such as providing specialized follow-up care, for example with postoperative care for patients who have undergone major surgery or recent hospitalization. This study assesses if community paramedics are a valid option in reducing rehospitalization of patients who underwent a coronary artery bypass grafting (CABG) procedure. Methods: A retrospective chart review between 2021 and 2022 was performed on all patients who underwent CABG in Bismarck, North Dakota, along with obtaining a referral for the community paramedics spanning urban and rural areas. A comparison was made between individuals who saw the community paramedics in their post-care versus those who continued with the standard of care. Results: There were 80 participants and 38 location-matched controls. All variables were found to be statistically insignificant except for the number of walk-in visits (urgent care), in which 7 out of 38 sought medical attention in the controls and 4 out of 80 sought medical attention in the participants. The proportions of inpatient readmission rates and emergency department (ED) visits were similar. Discussion: Given that paramedicine is in its infancy, the emergence of other variations of the community paramedic certification has brought a discussion of their scope of practice. While walk-in visits, even with the limitations, showed significant improvement with the addition of community paramedics, more research is still needed to show their effectiveness in reducing readmission to hospital. Additionally, the patients who sought help from community paramedics may be more likely than the controls to seek help from medical professionals. Conclusion: This study provided a novel look into the effect that community paramedics can have on patients in urban and rural areas in regard to reducing postoperative complications and minimizing unnecessary advanced healthcare utilization.

Mental health issues are a growing concern in the workplace, linked to negative outcomes including reduced productivity, increased absenteeism, and increased turnover. Employer-sponsored mental health benefits that are accessible and proactive may help address these concerns. The aim of this retrospective cohort study was to evaluate the impact of a digital mental health benefit (Spring Health) on frontline healthcare service workers' clinical and workplace outcomes. The benefit was sponsored by a national health services company from 2021-2022 and included mental health screening, care navigation, psychotherapy and/or medication management. We hypothesized program use would be associated with improvements in depression and anxiety symptoms, and increased productivity and retention. Participants were employees enrolled in the benefit program, had at least moderate anxiety or depression, at least 1 treatment appointment, and at least 2 outcome assessments. Clinical improvement measures were PHQ-9 scale (range, 0-27) for depression and GAD-7 scale (range, 0-21) for anxiety; workplace measures were employee retention and the Sheehan Disability Scale (SDS) for functional impairment. A total of 686 participants were included. Participants using the mental health benefit had a 5.60 point (95% CI, 4.40-6.79, d = 1.28) reduction in depression and a 5.48 point (95% CI, 3.88-7.08, d = 1.64) reduction in anxiety across 6 months. 69.9% (95% CI, 61.8%-78.1%) of participants reliably improved (≥5 point change) and 84.1% (95% CI, 78.2%-90.1%) achieved reliable improvement or recovery (

The rapid surge in perovskite solar cell efficiency has necessitated the development of viable metrology techniques during device integration, paving the way for commercialization. Ellipsometry is considered the most appropriate technique for fast and accurate thickness measurement for large scale production. However, a precise and well-calibrated model is a prerequisite for this technique. While ellipsometry of individual device layers has been reported in recent perovskite literature, a comprehensive multilayer modeling approach is thus far unavailable. Perovskite optoelectronic devices generally consist of a six-layer film stack with three transparent layers required for optical absorption in the perovskite layer. Spin casted thin films, now common in this line of research, impart their own difficulties into ellipsometric modeling. Roughnesses at each heterointerface, similarities in optical spectra of transparent layers, and anomalous dispersion of perovskite are just a few of such challenges. In this work, we report the process of building an ellipsometry model from scratch for thickness measurement of methylammonium lead iodide (MAPI) perovskite and indium tin oxide (ITO)/hole transport layer (HTL) bilayer thin film stacks on a glass substrate. Three promising representatives of HTLs (CuI, Cu2O, and PEDOT:PSS) were studied. The models were extended to measure the individual layer thicknesses of the MAPI/HTL/ITO film stack on a glass substrate using the models developed for individual layers. Optical constants of all the representative thin films were thus extracted for a wide wavelength range (300 nm–900 nm).

The structure of the dimer bis{tricarbonyl[η5-tetramethyl(phenethyl)cyclopentadienyl]molybdenum}(Mo—Mo), [Mo2(C17H21)2(CO)6], at 102 K has triclinic (P\overline{1}) symmetry. The reaction between tetramethyl(phenethyl)cyclopentadiene and molybdenum hexacarbonyl in refluxing xylenes for 18 h led to a 56% yield of the dimer as a red solid. The asymmetric unit of the structure is the tetramethyl(phenethyl)cyclopentadienylmolybdenumtricarbonyl moiety and the entire dimeric molecule is generated by inversion symmetry. The Mo—Mo bond length is 3.2773 (3) Å, a value slightly above the mean value for all [CpMo(CO)3]2 compounds listed in the CSD and slightly below the mean for [Cp*Mo(CO)3]2 complexes.

Abstract Background Strengthening Community Health Worker systems has been recognized to improve access to chronic disease prevention and management efforts in low-resource communities. The Community Outreach and Patient Empowerment (COPE) Program is a Native non-profit organization with formal partnerships with both the Navajo Nation Community Health Representative (CHR) Program and the clinical facilities serving the Navajo Nation. COPE works to better integrate CHRs into the local health care system through training, strengthening care coordination, and a standardized culturally appropriate suite of health promotion materials for CHRs to deliver to high-risk individuals in their homes. Methods The objective of this mixed methods, cross sectional evaluation of a longitudinal cohort study was to explore how the COPE Program has effected CHR teams over the past 6 years. COPE staff surveyed CHRs in concurrent years (2014 and 2015) about their perceptions of and experience working with COPE, including potential effects COPE may have had on communication among patients, CHRs, and hospital-based providers. COPE staff also conducted focus groups with all eight Navajo Nation CHR teams. Results CHRs and other stakeholders who viewed our results agree that COPE has improved clinic-community linkages, primarily through strengthened collaborations between Public Health Nurses and CHRs, and access to the Electronic Health Records. CHRs perceived that COPE’s programmatic support has strengthened their validity and reputation with providers and clients, and has enhanced their ability to positively effect health outcomes among their clients. CHRs report an improved ability to deliver health coaching to their clients. Survey results show that 80.2% of CHRs feel strongly positive that COPE trainings are useful, while 44.6% of CHRs felt that communication and teamwork had improved because of COPE. Conclusions These findings suggest that CHRs have experienced positive benefits from COPE through training. COPE may provide a useful programmatic model on how best to support other Community Health Workers through strengthening clinic-community linkages, standardizing competencies and training support, and structuring home-based interventions for high-risk individuals.

This article explores the concepts of community driven research and experiential learning in the context of partnerships between universities and indigenous communities. Specifically, this article examines the successes and challenges of Miami University’s partnership with the Eastern Shawnee Tribe of Oklahoma (ESTOO). Taking a dialogic approach, a professor, two students and a tribal leader, reflect on their experiences within the partnership and provide insight into how partnerships between universities and indigenous communities might develop, function, and serve both students and community members.

Posttransplantation lymphoproliferative disorder (PTLD) is a recognized and extremely morbid complication of solid organ transplantation, but central nervous system involvement, particularly in isolation, is rare. There are no standardized treatment strategies for PTLD, though commonly used strategies include reduction of immunosuppression, chemotherapy, rituximab, radiation, and surgery. We present a case of an unusual morphologic variant of primary central nervous system PTLD with successful response to rituximab and cranial radiation. A 69-year-old Asian male, who underwent postrenal transplant nine years earlier, presented with a one-month history of new onset seizure activity. His evaluation revealed multiple brain lesions on magnetic resonance imaging (MRI), as well as serologic and cerebrospinal fluid studies which were positive for Epstein-Barr Virus (EBV) infection. Ultimately, he underwent craniotomy with tissue biopsy with the final pathology report showing posttransplant lymphoproliferative disorder, polymorphic type. The patient was managed with reduction in immunosuppression, rituximab therapy, and cranial radiation treatments. He had demonstrated marked improvement in his neurologic function and was ultimately discharged to inpatient rehabilitation facility.

This study explores attitudes toward diphtheria-tetanus-acellular pertussis (DTaP), measles-mumps-rubella (MMR), influenza, and coronavirus disease 2019 (COVID-19) vaccines among English-speaking and Spanish-speaking parents of infants in a safety-net setting. Parents aged 18 years or older were recruited from outpatient clinics between December 2020 and December 2021. The interviews were then recorded, transcribed, translated, and qualitatively analyzed using the modified grounded theory. Thirty-two individuals participated (18 English-speaking and 14 Spanish-speaking). Almost all supported receiving routine childhood vaccines, DTaP, influenza, and MMR and believed that vaccines promote health. Vaccine concerns differed by each vaccine. Few participants expressed concerns about DTaP and MMR vaccines. Concerns around influenza vaccines often stemmed from personal experience and perceived increased risk of flu-like illnesses. Participants expressed the most concerns related to COVID-19 vaccinations, including age-based immunity of their infants. Based on these findings, future interventions to improve vaccine uptake may focus on benefits common to all vaccines, while addressing vaccine-specific concerns., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: This multicentered cohort study evaluated the radiographic outcomes of regenerative endodontic procedures (REPs) and apexification treatments (APEX) of immature teeth with endodontic disease., Materials and Methods: This cohort study included a retrospective record review and prospective data collection of pediatric patients with teeth treated with REPs or APEX between 2005 and 2014. Data including the presence of a periapical lesion, external root resorption, obliteration, apical hard tissue, apical closure, intracanal calcifications, and radiographic root area (RRA) change based on measurements were collected/measured from radiographic images. Univariate and multivariate analyses were conducted., Results: The cohort included 190 subjects (204 teeth (92 REPs; 112 APEX)). The frequency of pretreatment periapical pathology was similar between cases in which the clinical treatment failed versus successful treatment cases. However, the frequency of pretreatment external root resorption was higher in failed cases than in successful cases (P = .007). The mean RRA change was greater than twenty percent in 21% of the REPs cases. In traumatized teeth, REPs resulted in less hard tissue formation than other endodontic disease etiologies measured by RRA (P = .001). Fifty-three percent of cases with ERR (16/30) showed signs of healing/arrest and were mostly treated with REPs (11/16)., Conclusions: The presence of ERR negatively affected the treatment outcome. There was significant variability in RRA change in REPs. Signs of healing/arrest of the resorptive lesion were radiographically visible in many cases treated with REPs., (Copyright © 2024 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: Self-reported measures of periodontitis developed for use in population surveillance are increasingly used in causal research. Numerous studies evaluate the validity of these measures against clinical parameters of periodontitis, yet few include validation parameters outside of multivariable models. Individual item validity is necessary to adequately inform use of these measures in causal research., Methods: We used data from the National Health and Nutrition Examination Survey 2011-2014 in which dentate participants completed full-mouth periodontal examinations (N = 6966). We evaluated six self-report questionnaire items related to periodontal disease status against periodontitis case definitions developed by the Centers for Disease Control and Prevention and American Academy of Periodontology (CDC-AAP). We estimated the sensitivity and specificity of individual items using severe and moderate-to-severe periodontitis classifications. We additionally combined items to evaluate the validity of joint measures., Results: Sensitivity was highest when measures were evaluated against severe periodontitis. Self-rated oral health of fair/poor demonstrated the highest sensitivity for severe (0.60) and moderate-to-severe periodontitis (0.48). Specificity was highest when evaluated against moderate-to-severe periodontitis, with self-reported history of tooth mobility as the most specific measure (0.87 for severe disease; 0.92 for moderate-to-severe) followed by a history of bone loss (0.88 for severe; 0.91 for moderate-to-severe). Combining questions generally improved specificity at the expense of sensitivity., Conclusions: Our findings related to item-specific validity and the associated clinical profiles facilitate needed considerations for the use of self-reported measures of periodontitis in causal research. Additionally, item-specific validity can be used to inform assessments of misclassification bias within such investigations., (© 2024 American Academy of Periodontology.)

Objective: To understand attitudes towards telemedicine and to further elucidate benefits, disadvantages, and visit preferences in a largely minority, urban safety-net setting., Methods: Between 2020 and 2021, pregnant people, and parents of children younger than two years old were recruited from outpatient clinics. Interviews were conducted via phone, recorded, transcribed, and translated. Data were analyzed using content analysis., Results: Seventy-four (74) individuals participated including 42 pregnant people and 32 parents. Most participants cited advantages to telemedicine including safety, convenience, improved access, and less disruption of work schedules, and wished to continue to have the telemedicine option available after the pandemic., Conclusions: Patients seeking care in safety-net settings, many of whom are working parents, noted that telemedicine improves access to care by providing an efficient and accessible option that overcomes barriers related to transportation and work schedules. Their experiences highlight the importance of continuing to offer telemedicine services.

Pain from bacterial infection was believed to be the consequence of inflammation induced by bacterial products. However recent studies have shown that bacterial products can directly activate sensory neurons and induce pain. The mechanisms by which bacteria induce pain are poorly understood, but toll-like receptor (TLR)4 and transient receptor potential A1 (TRPA1) receptors are likely important integrators of pain signaling induced by bacteria. Using male and female mice we show that sensory neuron activation by bacterial lipopolysaccharides (LPS) is mediated by both TRPA1 and TLR4 and involves the mobilization of extracellular and intracellular calcium. We also show that LPS induces neuronal sensitization in a process dependent on TLR4 receptors. Moreover, we show that TLR4 and TRPA1 are both involved in sensory neurons response to LPS stimulation. Activation of TLR4 in a subset of sensory neurons induces TRPA1 upregulation at the cell membrane through vesicular exocytosis, contributing to the initiation of neuronal sensitization and pain. Collectively these data highlight the importance of sensory neurons to pathogen detection, and their activation by bacterial products like LPS as potentially important to early immune and nociceptive responses. SIGNIFICANCE STATEMENT Bacterial infections are often painful and the recent discovery that bacteria can directly stimulate sensory neurons leading to pain sensation and modulation of immune system have highlighted the importance of nervous system in the response to bacterial infection. Here, we showed that lipopolysaccharide, a major bacterial by-product, requires both toll-like receptor (TLR)4 and transient receptor potential A1 (TRPA1) receptors for neuronal activation and acute spontaneous pain, but only TLR4 mediates sensory neurons sensitization. Moreover, we showed for the first time that TLR4 sensitize sensory neurons through a rapid upregulation of TRPA1 via vesicular exocytosis. Our data highlight the importance of sensory neurons to pathogen detection and suggests that TLR4 would be a potential therapeutic target to modulate early stage of bacteria-induced pain and immune response., (Copyright © 2023 the authors.)

To explore the mental health impacts of the COVID-19 pandemic on healthcare workers in Massachusetts and identify potential strategies to maintain the healthcare workforce we conducted a sequential exploratory mixed methods study. Fifty-two individuals completed interviews from April 22nd - September 7th, 2021; 209 individuals completed an online survey from February 17th - March 23rd, 2022. Interviews and surveys asked about the mental health impacts of working in healthcare during the COVID-19 pandemic, burnout, longevity in the workplace, and strategies for reducing attrition. Interview and survey participants were predominantly White (56%; 73%, respectively), female (79%; 81%) and worked as physicians (37%; 34%). Interviewees indicated high stress and anxiety levels due to frequent exposure to patient deaths from COVID-19. Among survey respondents, 55% reported worse mental health than before the pandemic, 29% reported a new/worsening mental health condition for themselves or their family, 59% reported feeling burned out at least weekly, and 37% intended to leave healthcare in less than 5 years. To decrease attrition, respondents suggested higher salaries (91%), flexible schedules (90%), and increased support to care for patients (89%). Healthcare workers' experiences with death, feeling unvalued, and overworked resulted in unprecedented rates of burnout and intention to leave healthcare., Competing Interests: The authors report there are no competing interests to declare., (© 2023 Published by Elsevier Inc.)

Objective: To explore attitudes toward tetanus-diphtheria-acellular pertussis (Tdap), influenza, and COVID vaccines among English- and Spanish- speaking pregnant individuals in a safety net setting., Methods: Pregnant people aged 18 years or older were recruited from outpatient clinics between August 2020 and June 2021. Interviews were conducted via phone in English or Spanish, recorded, transcribed, and translated verbatim. Data were qualitatively analyzed using modified grounded theory and content analysis., Results: 42 patients participated (22 English-speaking, 20 Spanish-speaking). Most participants expressed positive attitudes towards both routine prenatal vaccinations and COVID-19 vaccines, endorsing the belief that vaccines promote health and considering vaccines a social norm. Positive attitudes were similar for the three vaccines, and among Spanish- and English-speaking individuals. Participants trusted their healthcare provider's recommendations and felt comfortable receiving booster doses of vaccines they had received successfully in the past. Vaccine concerns differed by each vaccine. Despite limited knowledge, few participants expressed concerns about Tdap vaccines. Concerns around influenza vaccines often stemmed from personal experience and centered around ineffectiveness and increased risk of flu-like illnesses. Participants expressed the most concerns related to COVID vaccinations, including misinformation about serious side effects and distrust around accelerated approval of the vaccines. Many participants wished to know more about the side effects and safety of vaccinating during pregnancy, especially regarding the fetus's health., Conclusions: Most participants supported routine prenatal vaccinations, including COVID vaccines. Clinicians are trusted information sources and can help reinforce positive attitudes and social norms of receiving vaccinations in pregnancy while addressing vaccine-specific concerns., Funding: This work was supported by Suzanne Cutler Vaccination Education & Research Fund at the Boston University Chobanian and Avedisian School of Medicine for funding and support., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2023 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Biomarkers assayed from gingival crevicular fluid (GCF) are a potential tool for endodontic diagnosis and for monitoring treatment response. This cross-sectional study measured cytokines in GCF from teeth with apical periodontitis and evaluated their relationship with preoperative pain and other clinical findings., Methods: Participants presenting for root-end resection surgery due to apical periodontitis diagnosis (n = 56) underwent standardized clinical testing and completed preoperative questionnaires. GCF from diseased and control teeth were collected, processed, and analyzed. Mann-Whitney U and Wilcoxon tests were used to examine the cytokine levels in diseased compared to healthy control teeth. We also assessed the relationship of cytokine levels with clinical findings., Results: Interleukins (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ, and tumor necrosis factor-⍺ (TNF-⍺) were detected in GCF. TNF-⍺ levels were significantly higher in GCF collected from diseased versus control teeth (P = .02) and increased IL-1β levels in diseased teeth were detected (P = .06). Lower IL-10 levels were observed in teeth with a sinus tract and/or swelling compared to teeth without a sinus tract and/or swelling (P = .08). Cytokine levels did not clearly relate to the presence of pain., Conclusions: Elevated levels of proinflammatory cytokines, including TNF-⍺ and IL1- β, were detected in GCF from diseased teeth compared to the healthy controls. Additional studies are needed to further investigate the utility of these biomarkers for objectively evaluating periradicular pathology., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: Oral health care professionals are well positioned to contribute to the prevention of human papillomavirus (HPV)-related oropharyngeal and other HPV-related cancers through engaging patients in conversations about HPV vaccination. This scoping review evaluates evidence regarding oral health care provider knowledge of, and discussion related to, HPV prevention, transmission, and associated risks, including oropharyngeal cancer. This review outlines relevant barriers to, and facilitators of, this knowledge and discussion. In addition, to determine the potential population that could be reached by an oral health care provider for a conversation about HPV vaccination, this review evaluates the prevalence of HPV vaccination as well as dental visits in a US population., Types of Studies Reviewed: Four databases were systematically searched (MEDLINE [PubMed], EMBASE, APA PsycInfo, Cumulative Index to Nursing and Allied Health Literature). Studies written in English and conducted in the United States were eligible. Eligibility criteria were not restricted to publication year or oral health care provider type. Behavioral Risk Factor Surveillance System 2018 data were analyzed to evaluate the prevalence of HPV vaccination and dental visits among patients aged 18 through 49 years., Results: After duplicate record removal and second-stage screening, 32 full-text articles were retrieved, and data were independently extracted by 2 reviewers. Twenty-four studies were included in this review. Knowledge regarding HPV prevalence, transmission, disease processes, and risks varied. In general, discussions related to HPV in dental settings were infrequent. Facilitators to improve knowledge and discussion included guidance from professional dental organizations, education, and communication skills. Behavioral Risk Factor Surveillance System data showed that most people who are not vaccinated have visited their oral health care providers in the past year, highlighting the potential role of oral health care providers regarding discussion of HPV and promoting awareness and acceptance of vaccination., Conclusions and Practical Implications: This review indicates that discussions related to HPV were infrequent in the oral health care setting, which may be related to lack of knowledge and communication skills among oral health care professionals; however, evidence exists supporting the interest of oral health care professionals in improving vaccine uptake to prevent oropharyngeal cancer., (Copyright © 2023 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Aim: To examine experiences and attitudes of a diverse sample of clinical and non-clinical healthcare workers regarding COVID-19 vaccines and boosters for themselves, their patients, and their communities., Subject and Methods: We conducted a sequential exploratory mixed methods study; 52 healthcare workers participated in qualitative interviews between April 22 and September 7, 2021, and 209 healthcare workers completed surveys between February 17 and March 23, 2022. Interviews and survey questions asked about personal attitudes toward COVID-19 vaccination and boosters and experiences discussing vaccination with patients., Results: Participants were predominantly White (56% and 73%, respectively) and female (79% and 81%, respectively). Factors motivating healthcare workers to take the vaccine were the belief that vaccination would protect themselves, their families, patients, and communities. Healthcare workers were accepting of and had high receipt of the booster, though some had diminished belief in its effectiveness after becoming infected with SARS-CoV-2 after initial vaccination. Race related mistrust, misinformation related to vaccine safety, and concerns about vaccine effects during pregnancy were the most common barriers that providers encountered among their patients and communities., Conclusions: Healthcare workers' primary motivation to receive COVID-19 vaccines was the desire to protect themselves and others. Healthcare workers' perception was that concerns about safety and misinformation were more important barriers for their patients than themselves. Race-related medical mistrust amplified concerns about vaccine safety and hindered communication efforts., Competing Interests: Conflicts of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Understanding the association of prior SARS-CoV-2 infection with subsequent reinfection has public health relevance., Objective: To explore COVID-19 severity and SARS-CoV-2 infection and reinfection rates., Design: Retrospective cohort study., Setting: Boston, Massachusetts, during the first COVID-19 surge (01/01/2020-05/31/2020; Period-1) and after the first surge (06/01/2020-02/28/2021; Period-2); Period-2 included the second surge (11/01/2020-02/28/2021)., Participants: Patients in an academic medical center and six community health centers who received a clinical diagnosis of COVID-19 between 01/01/2020 and 05/31/2020 or SARS-CoV-2 testing between 01/01/2020 and 02/28/2021., Measurements: COVID-19 severity was compared between Period-1 and Period-2. Poisson regression models adjusted for demographic variables, medical comorbidities, and census tract were used to assess reinfection risk among patients with COVID-19 diagnoses or SARS-CoV-2 testing during Period-1 and additional SARS-CoV-2 testing during Period-2., Results: Among 142,047 individuals receiving SARS-CoV-2 testing or clinical diagnoses during the study period, 15.8% were infected. Among COVID-19 patients, 22.5% visited the emergency department, 13% were hospitalized, and 4% received critical care. Healthcare utilization was higher during Period-1 than Period-2 (22.9% vs. 18.9% emergency department use, 14.7% vs. 9.9% hospitalization, 5.5% vs. 2.5% critical care; p  < 0.001). Reinfection was assessed among 8961 patients with a SARS-CoV-2 test or COVID-19 diagnosis in Period-1 who underwent additional testing in Period-2. A total of 2.7% ( n  = 65/2431) with SARS-CoV-2 in Period-1 tested positive in Period-2, compared with 12.6% ( n  = 821/6530) of those who initially tested negative (IRR of reinfection = 0.19, 95% CI: 0.15-0.25)., Conclusions: Prior SARS-CoV-2 infection among this observational cohort was associated with an 81% lower reinfection rate., Competing Interests: No authors have conflicts of interest to declare., (© 2022 The Authors.)

Healthcare workers are a trusted health information source and are uniquely positioned to reduce the burden of the COVID-19 pandemic. The purpose of this sequential exploratory mixed methods study was to understand attitudes of healthcare workers working in Massachusetts during the COVID-19 pandemic regarding strategies to improve COVID-19 vaccine utilization, including vaccine mandates and incentives. Fifty-two individuals completed one-on-one interviews between April 22 nd and September 7th, 2021. The survey was developed based on findings from the interviews; 209 individuals completed the online survey between February 17 th and March 23 rd , 2022. Both the interview and survey asked about attitudes toward COVID-19 vaccine and booster mandates, incentives, and strategies to improve vaccination rates. Most participants were female (79%-interview, 81%-survey), Caucasian (56%, 73%), and worked as physicians (37%, 34%) or nurses (10%, 18%). Overall, nuanced attitudes regarding vaccine and booster mandates were expressed; many supported mandates to protect their patients' health, others emphasized personal autonomy, while some were against mandates if job termination was the consequence of declining vaccines. Similarly, views regarding vaccine incentives differed; some considered incentives helpful, yet many viewed them as coercive. Strategies believed to be most effective to encourage vaccination included improving accessibility to vaccination sites, addressing misinformation, discussing vaccine safety, tailored community outreach via trusted messengers, and one-on-one conversations between patients and healthcare workers. Healthcare workers' experiences with strategies to improve utilization of COVID-19 vaccines and boosters have implications for public health policies. Generally, efforts to improve access and education were viewed more favorably than incentives and mandates.

The ability to regenerate damaged cartilage capable of long-term performance in an active joint remains an unmet clinical challenge in regenerative medicine. Biomimetic scaffold biomaterials have shown some potential to direct effective cartilage-like formation and repair, albeit with limited clinical translation. In this context, type II collagen (CII)-containing scaffolds have been recently developed by our research group and have demonstrated significant chondrogenic capacity using murine cells. However, the ability of these CII-containing scaffolds to support improved longer-lasting cartilage repair with reduced calcified cartilage formation still needs to be assessed in order to elucidate their potential therapeutic benefit to patients. To this end, CII-containing scaffolds in presence or absence of hyaluronic acid (HyA) within a type I collagen (CI) network were manufactured and cultured with human mesenchymal stem cells (MSCs) in vitro under chondrogenic conditions for 28 days. Consistent with our previous study in rat cells, the results revealed enhanced cartilage-like formation in the biomimetic scaffolds. In addition, while the variable chondrogenic abilities of human MSCs isolated from different donors were highlighted, protein expression analysis illustrated consistent responses in terms of the deposition of key cartilage extracellular matrix (ECM) components. Specifically, CI/II-HyA scaffolds directed the greatest cell-mediated synthesis and accumulation in the matrices of type II collagen (a principal cartilage ECM component), and reduced deposition of type X collagen (a key protein associated with hypertrophic cartilage formation). Taken together, these results provide further evidence of the capability of these CI/II-HyA scaffolds to direct enhanced and longer-lasting cartilage repair in patients with reduced hypertrophic cartilage formation.

Introduction: This multicentered cohort study evaluated factors associated with patient-centered outcomes of immature permanent teeth that received regenerative endodontic procedures (REPs) or apexification treatment (APEX)., Methods: A record review identified teeth treated with REPs or APEX between September 2005 and December 2014. Data regarding treatment and patient-centered outcomes were extracted from records with a 3-month minimum recall. When possible, participants presented for an in-person prospective research visit. Patient-centered success was defined as an asymptomatic, functional tooth not requiring further endodontic or surgical intervention after completion of the original treatment during the study observation. Risk ratios and adjusted and unadjusted Cox proportional hazard ratios were calculated., Results: The analytic cohort of 187 individuals included 211 teeth (93 REPs and 118 APEX) with an average follow-up of 32 months. Most cases were successful (81% REPs and 92% APEX) and survived the observation period (96% REPs and 97% APEX). The success rate of REPs was lower than APEX and decreased more rapidly over time. Cox regression analysis demonstrated that when controlling for other variables, the association between treatment type and outcome is not significant. Preoperative infection, teeth with more immature roots, and REP treatment are potentially important predictors. Among teeth receiving REPs, a lower failure rate was observed for teeth that received multiantibiotic paste (3/43) compared with calcium hydroxide (11/45)., Conclusions: Teeth receiving REPs required clinical intervention earlier than teeth that received APEX treatment, although a preoperative abscess and more immature root also affected this outcome. Using multiantibiotic paste versus calcium hydroxide in REPs may improve success., (Copyright © 2021. Published by Elsevier Inc.)

Background: Approximately 11% of 18-25 year-olds report thoughts of suicide. Additionally, suicide is the second leading cause of death in college student populations. We sought to evaluate the relationship between diagnosed mental health conditions and current symptoms of depression and/or anxiety and suicidality in the past year., Methods: Healthy Minds Study (HMS) 2018-2019 data from 38,757 college students were analyzed. The PHQ-9, GAD-7, and prior mental health condition diagnoses were used to create a suicidality severity index and we determined how these associations varied by race/ethnicity, gender, and sexual orientation. We also assessed non-suicidal self-injury (NSSI) outcomes in the past year., Results: Students with both a mental health condition diagnosis and current moderate/severe symptoms of depression and/or anxiety had a higher prevalence of NSSI, 10 times the odds (95% CI 9.4-11.5) of suicide ideation, 28 times the odds (95% CI 23.8-33.1) of suicide ideation, with planning or attempt, and 47 times the odds (95% CI 31.1-71.4) of suicide ideation, with planning and attempt, compared to students with none/minimal depression and/or anxiety symptoms and no mental health condition diagnosis., Limitations: We could not clinically confirm depression or anxiety diagnoses nor infer causality of associations in this cross-sectional study. Future longitudinal studies are needed to establish temporality., Conclusions: Mental health condition diagnoses and moderate/severe symptoms of depression and/or anxiety were strongly associated with suicidality among college students. These findings identify potential opportunities to further understand and address the mental health needs of college students., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: The aim of the study was to evaluate the long-term sustainability of a multilevel intervention and the COVID-19 pandemic impact on adolescent human papillomavirus (HPV) vaccination coverage., Materials and Methods: In 2016, a pediatric and family medicine practice within a federally qualified health center completed a multilevel intervention, Development of Systems and Education for Human Papillomavirus Vaccination. We examined the intervention impact on HPV vaccine initiation and completion rates among adolescents 10-18 years between March 2016 and October 2020. We determined the total number of HPV vaccine doses administered monthly. Data were plotted on statistical process control charts., Results: Vaccine initiation increased from an average of 14% to an average of 42% for 10-year-old patients and from an average of 72% to an average of 92% for 11- to 12-year-old patients between March 2016 and January 2017 and remained stable through March 2020. Complete vaccination by age 13 years increased from 62% to 88% through October 2020., Conclusions: This intervention led to continued improvement for on-time HPV vaccination coverage 4 years after intervention completion.Clinical Trial Registration: This trial has been registered at http://www.clinicaltrials.gov (identifier NCT02812732)., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2021, ASCCP.)

Dental pulp stem cells (DPSCs) are important in tooth physiology, contributing to development, repair, regeneration, and immunomodulatory processes. However, their role in inflammatory mechanisms underlying pulpitis is not well understood. We evaluated the influence of DPSCs stimulated with calcitonin gene-related peptide (CGRP), a proinflammatory neuropeptide, on the expression of mediators released from DPSCs and the effect of these mediators on sensory neuron activity. Human DPSCs were treated with either control media or media containing CGRP (10 -8  M) for 7 d, and the conditioned media (CM) containing DPSC-released mediators was collected. The expression of cytokines and chemokines from DPSCs was evaluated by reverse transcription quantitative polymerase chain reaction. The effects of the CM from CGRP-primed DPSCs (primed DPSC-CM) were evaluated on sensory afferents by using primary cultures of mouse trigeminal neurons and an organotypic model of cultured human pulp slices. Mouse trigeminal neurons and human pulp explants were pretreated for 24 h with control or primed DPSC-CM and then stimulated with capsaicin. Afferent activity was measured by quantifying the response to capsaicin via live cell calcium imaging in mouse neurons and CGRP released from pulp explants. Gene expression analysis showed that primed DPSCs overexpressed some proinflammatory cytokines and chemokines, including chemokines CXCL1 and CXCL8, which are both agonists of the receptor CXCR2 expressed in sensory neurons. Primed DPSC-CM increased human pulp sensory afferent activity as compared with control DPSC-CM. Similarly, primed DPSC-CM increased the intensity of calcium responses in cultured mouse trigeminal neurons. Furthermore, the CXCR2 antagonist SB225002 prevented trigeminal neuron sensitization to capsaicin induced by primed DPSC-CM. In conclusion, mediators released by DPSCs, primed with the proinflammatory mediator CGRP, induce neuronal sensitization through CXCR2 receptor. These data suggest that DPSCs might contribute to pain symptoms that develop in pulpitis.

Joint repair remains a major challenge in orthopaedics. Recent progress in biomaterial design has led to the fabrication of a plethora of promising devices. Pre-clinical testing of any joint repair strategy typically requires the use of large animal models (e.g., sheep, goat, pig or horse). Despite the key role of such models in clinical translation, there is still a lack of consensus regarding optimal experimental design, making it difficult to draw conclusions on their efficacy. In this context, the authors performed a systematic literature review and a risk of bias assessment on large animal models published between 2010 and 2020, to identify key experimental parameters that significantly affect the biomaterial therapeutic outcome and clinical translation potential (including defect localization, animal age/maturity, selection of controls, cell-free versus cell-laden). They determined that mechanically strong biomaterials perform better at the femoral condyles; while highlighted the importance of including native tissue controls to better evaluate the quality of the newly formed tissue. Finally, in cell-laded biomaterials, the pre-culture conditions played a more important role in defect repair than the cell type. In summary, here they present a systematic evaluation on how the experimental design of preclinical models influences biomaterial-based therapeutic outcomes in joint repair., (© 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

The purpose of this follow-up Delphi survey was to have an expert panel of 31 academic geriatric physicians, geriatric nurses, and medical directors of nursing homes evaluate the original timeline set to avoid oral neglect of nursing home residents. The Oral Neglect in Institutionalized Elderly (ONiIE) timelines defined oral neglect as having occurred when >7 days for acute oral diseases/conditions or >34 days for chronic oral disease/conditions had passed between initial diagnosis and offering access to dental care to the long-term care (LTC) nursing home resident. The results of this follow-up Delphi survey validated those originally defined ONiIE timelines as 90% of this panel agreed with the original timelines. This ONiIE definition adds a broad-based validation for the ONiIE timelines for setting an oral health standard of care for institutionalized elderly residents of nursing homes and should now be used to protect the vulnerable elderly residing in LTC nursing homes.

Due to the limited regenerative capacity of cartilage, untreated joint defects can advance to more extensive degenerative conditions such as osteoarthritis. While some biomaterial-based tissue-engineered scaffolds have shown promise in treating such defects, no scaffold has been widely accepted by clinicians to date. Multi-layered natural polymer scaffolds that mimic native osteochondral tissue and facilitate the regeneration of both articular cartilage (AC) and subchondral bone (SCB) in spatially distinct regions have recently entered clinical use, while the transient localized delivery of growth factors and even therapeutic genes has also been proposed to better regulate and promote new tissue formation. Furthermore, new manufacturing methods such as 3D bioprinting have made it possible to precisely tailor scaffold micro-architectures and/or to control the spatial deposition of cells in requisite layers of an implant. In this way, natural and synthetic polymers can be combined to yield bioactive, yet mechanically robust, cell-laden scaffolds suitable for the osteochondral environment. This mini-review discusses recent advances in scaffolds for osteochondral repair, with particular focus on the role of natural polymers in providing regenerative templates for treatment of both AC and SCB in articular joint defects., (© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

An understanding of the role that spin states play in semiconductor surface chemical reactions is currently limited. Herein, we provide evidence of a nonadiabatic reaction involving a localized singlet to triplet thermal excitation of the Si(100) surface dimer dangling bond. By comparing the β-hydrogen elimination kinetics of ethyl adsorbates probed by thermal desorption experiments to electronic structure calculation results, we determined that a coverage-dependent change in mechanism occurs. At low coverage, a nonadiabatic, inter-dimer mechanism is dominant, while adiabatic mechanisms become dominant at higher coverage. Computational results indicate that the spin crossover is rapid near room temperature and the nonadiabatic path is accelerated by a barrier that is 40 kJ mol -1 less than the adiabatic path. Simulated thermal desorption reactions using nonadiabatic transition state theory (NA-TST) for the surface dimer intersystem crossing are in close agreement with experimental observations.

Introduction: Pulpitis is an inflammation of dental pulp caused by bacterial proliferation near or within pulpal tissues. In advanced stages, when the inflammation is associated with pulp necrosis, pulp preservation is dependent on dental pulp stem cells (DPSCs) that can differentiate into odontoblastlike cells and produce reparative dentin. In this study, we evaluated the influence of sensory neurons through calcitonin gene-related peptide (CGRP) on DPSC viability and proliferation and the ability of DPSCs to differentiate into mineralizing cells., Methods: Commercially available DPSCs were treated with varying doses of CGRP, and metabolic activity, viability, proliferation, and cell death were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays, trypan blue staining, 5-bromo-2'-deoxyuridine cell proliferation assay, and caspase-3 staining, respectively. DPSC differentiation was assessed with alizarin red staining and by quantifying messenger RNA expression of odontoblast makers., Results: CGRP induced a dose-dependent decrease of DPSC metabolic activity that was prevented by the CGRP receptor antagonist CGRP 8-37. The decrease in the proportion of live cells induced by CGRP is associated with a decrease of cell proliferation but not with caspase-3-dependent apoptosis. Interestingly, dexamethasone-induced DPSC differentiation into mineralizing cells was neither inhibited nor enhanced by CGRP treatment., Conclusions: The neuropeptide CGRP has an inhibitory effect on DPSC proliferation but does not enhance or inhibit the differentiation of DPSCs into mineralizing cells. This suggests that CGRP might negatively influence the ability of DPSCs to contribute to regenerative or tissue repair processes., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Dominant follicles are those that continue to develop and have the potential to ovulate while subordinate follicles regress. Characteristics of dominant follicles include a larger diameter, higher intrafollicular estradiol, and lower IGF-binding protein (IGFBP)-4 concentrations compared with other cohort follicles. Follicle development is regulated by endocrine hormones that act via intracellular signaling pathways. Here, we show the differences in Akt, Erk, c-Jun N-terminal protein kinase, and p-38 signaling pathways between dominant and subordinate follicles at the dominance stage of the follicle wave. However, earlier in the follicle wave (dominant follicle selection), there were only differences in the levels of Akt and Erk signal transduction proteins among dominant and subordinate follicles. Using this profile of Akt and Erk protein expression in granulosa and theca cells of selected dominant follicles compared with subordinate follicles, we suggest a predictive model to identify future dominant and subordinate follicles from the pool of otherwise similar cohort follicles at the time of follicle wave emergence. We conclude that the Erk and Akt signal transduction pathways are important for dominant follicle selection and development and, furthermore, that the observed differences in these pathways mark the future dominant follicle from subordinate follicles before differences in follicular diameter, follicular fluid estradiol, and IGFBP-4 concentrations are apparent.

In 2005, approximately 211,240 women in the US will be diagnosed with early stage breast cancer and an estimated 22% will be child rearing. Research reveals that both mothers and children have elevated distress attributed to the cancer; struggle with how to talk about and deal with the impact of the cancer; and both fear the mother will die. The Enhancing Connections Program (EC) was developed to reduce this cancer-related distress and morbidity. The program involves five, 1-hour educational counseling sessions delivered at 2-week intervals by specially trained clinicians. This study reports on the program's short-term impact on mothers' and children's adjustment. Thirteen households were recruited within 7.5 months of the mother's diagnosis with early stage breast cancer. Impact was evaluated within a single group design using data obtained from standardized questionnaires with established reliability and validity. Results revealed significant improvements in the mother's depressed mood, anxiety, and self-confidence to assist her child (mother report). There were also significant decreases in the child's behavioral problems (mother and father report); the child's cancer-related worries (child report); and the child's anxiety/depressed mood (mother and father report). Further evaluation is warranted within a clinical trial.

The arterial baroreflex control of renal sympathetic nerve activity (RSNA) was evaluated in nine term pregnant (P) and 12 nonpregnant (NP) conscious New Zealand White rabbits. In an additional four P rabbits, the RSNA response to spontaneous parturition was measured. The blood pressure (BP)-RSNA relationship was generated by sequential inflations of aortic and vena caval perivascular occluders. Rest BP (P: 61 +/- 2 vs. NP: 73 +/- 2 mmHg) and the centering point of the baroreflex (P: 57 +/- 2 vs. NP: 70 +/- 2 mmHg) were lower (P < 0.05) in term pregnancy. Baroreflex range (P: 246 +/- 14% vs. NP 263 +/- 24% of rest RSNA) was not affected by pregnancy. However, maximal reflex gain was moderately depressed (-44%) in P rabbits (P: -15 +/- 1 vs. NP: -27 +/- 4% of rest RSNA/mmHg; P < 0.05) due to a significant reduction in the slope coefficient. Delivery of a fetus was associated with strong renal sympatho-excitation. Peak RSNA averaged 80 +/- 37% of smoke-elicited RSNA or 1,221 +/- 288% of rest RSNA (mean +/- SD). These results suggest that, in contrast to rat pregnancy, depressed arterial baroreflex control of RSNA in rabbit pregnancy is due primarily to a reduction in maximal gain rather than a reduction in the maximal sympathetic response to hypotension.

Activation of the muscle chemoreflex increases sympathetic drive to skeletal muscle in humans. This study investigated whether activation of the muscle chemoreflex augments the renal sympathetic nerve activity (RSNA) response to dynamic exercise in rabbits. The muscle chemoreflex was evoked by hindlimb ischemia during exercise on a motorized treadmill. Seven New Zealand White rabbits performed a nonischemic control protocol and a hindlimb ischemia protocol in which terminal aortic blood flow (Qta) was reduced to 51 +/- 2% of preocclusion Qta by partial aortic occlusion after 1.5 min of exercise. Mean arterial pressure (MAP), heart rate, RSNA and Qta increased in response to exercise and were similar between trials during the first 1.5 min of exercise. In the control trial, Qta, MAP, and RSNA were stable at an elevated level through an additional 3.5 min of exercise. Hindlimb ischemia produced a potent pressor response that plateaued after 2.5 min (delta + 17 +/- 4 mmHg, where delta designates change). RSNA began to increase after 1.5 min of ischemic exercise and was significantly elevated relative to preocclusion RSNA at 2.5 (delta + 25 +/- 9%) and 3.5 (delta + 47 +/- 12%) min of occlusion. These results suggest that the muscle chemoreflex can augment sympathoexcitatory drive to the kidney during dynamic exercise.

A novel multidrug resistance modulator, RS-33295-198, circumvented drug resistance in human, mouse, and Chinese hamster cell lines overexpressing P-glycoprotein. It enhanced the antiproliferative activity of doxorubicin, vincristine, etoposide, and paclitaxel and increased doxorubicin retention in multidrug-resistant hamster CHRC5 cells. RS-33295-198 modulated doxorubicin resistance in a murine P388/ADR leukemia model when administered ip via continuous minipump delivery, ip by bolus injection, and orally; it also improved the efficacy of vincristine toward P388/VCR leukemia when given ip or po. RS-33295-198 showed weak activity in enhancing doxorubicin efficacy against a multidrug-resistant human sarcoma xenograft.

Co-administration of doxorubicin and verapamil in Alzet mini-osmotic pumps increased the survival of B6D2F1 mice bearing the multidrug-resistant P388/ADR leukemia. A range of doxorubicin and verapamil combinations was studied to define dose-dependent efficacy and toxicity. High doses of doxorubicin (10 mg/kg/day) and verapamil (150 mg/kg/day) could be administered alone without any effect on survival. However, combining high doses of these two agents resulted in host toxicity. Doxorubicin doses of 1 to 10 mg/kg/day in combination with verapamil at 25-100 mg/kg/day were found to improve survival compared with either agent alone. Combination therapy also improved the survival of mice bearing the drug-sensitive P388/0 leukemia when compared to anthracycline treatment alone. The efficacy of the mini-osmotic pump delivery protocol was compared with other regimens delivering the same total cumulative dose of doxorubicin via repeated i.p. injections.

A study was conducted to evaluate mobile roadside speedometers as a means of controlling urban traffic speeds under varied schedules of deployment and speed limit law enforcement. Speeds of cars passing the roadside speedometer were measured using nondetectable radar. The data indicate that, generally, the speedometer's presence reduced average traffic speeds by about 10% alongside the speedometer and about 7% at short distances downstream. The proportion of drivers exceeding the speed limit by at least 10 mph fell dramatically from 15%-20% to only 2% at one site on days the speedometer was deployed, and the device was particularly effective when deployed in school zones. However, the effect of the speedometer was limited to the times when it was actually deployed. Associated police enforcement is a key factor, as the effect of the speedometer decayed over time but could be long lasting with a minimal amount of enforcement activity in the area of the speedometer.

The changes in tissue Mn, Cu, Fe, Zn, and Superoxide dismutase (SOD) activity were studied in control and Mn-deficient mice during postnatal development. Mn levels were lower in tissues from Mn-deficient mice than in controls throughout development. By day 60, Mn concentration in tissues from Mn-deficient mice was at least 70% lower than that of controls. Cu levels in the two groups did not differ appreciably. Liver Cu concentration was highest at day 5, then decreased. Heart and kidney Cu increased throughout development. Fe concentration in heart and liver was similar in both groups at 1, 5, and 20 days of age, but at day 60, kidney Fe in the Mn-deficient mice was 40% higher than in controls. The developmental pattern for MnSOD activity paralleled that of Mn concentration. At day 5, there were no differences in MnSOD activity between control and deficient mice. By day 60, MnSOD activity in most tissues was at least 50% lower than that of controls, possibly increasing the susceptibility of the Mn deficient animal to oxidative damage.These developmental patterns should help investigators to determine the tissues and time periods in which to study trace element metabolism.

An investigation was undertaken to determine if the lateral placement of a visual stimulus, and the observer's consequential eye-gaze position while orienting towards the stimulus, affects the observer's response to the stimulus. It was predicted that a lateral positioning of the eye-gaze would facilitate cerebral processing in the hemisphere contralateral to the direction of the eye-gaze. Because each hemisphere is generally specialized for certain types of processing, it was theorized that responses to "verbal" problems would be augmented when placed 20 degrees to the right of center as opposed to 20 degrees to the left of center; and that responses to "spatial" problems would be aided when the stimuli were located 20 degrees to the left of center as opposed to 20 degrees to the right of center. Twenty-four right-handed male and female adults served as subjects. Verbal problems consisted of a comparison of capital and noncapital letters. Spatial stimuli consisted of dot-and-square diagrams. In toto, the results of the performance tests are in partial support of the theory.

Immunocytochemical studies on the localization of peptides at the ultrastructural level have most frequently involved the application of the peroxidase--antiperoxidase (PAP) method of immunocytochemistry and the use of the preembedding or postembedding staining procedures. The present study was designed to determine the depth of penetration of Vibratome tissue sections by immunoreagents used in the preembedding method in which immunostaining of unembedded fixed tissue sections is accomplished prior to tissue dehydration and embedment. Our data indicate that penetration of immunoreagents is restricted to the superficial 8-9 micrometers of a 80-micrometers thick Vibratome tissue section of hypothalamus of brain using antisera generated against arginine vasopressin. The final immunoreaction product visualized in a Vibratome tissue section may reflect only a fraction of the amount of hormone contained within the thickness of the tissue section.

Altered trace elements and ascorbic acid metabolism have been implicated in the pathogenesis of atherosclerotic cardiovascular disease. However, their role in the disease process, or the effect of atherosclerosis on their tissue levels within plaque, is poorly understood. The present study analyzes the concentrations of Fe, Cu, Zn, and Mn, and ascorbic acid and superoxide dismutase (SOD) activity in tissue samples from 29 patients with abdominal aortic aneurysms (AAA) and 14 patients with atherosclerotic occlusive disease (AOD). It was observed that the Fe and Mn concentrations in AAA and AOD tissue were higher than the levels in nondiseased control aorta, whereas Cu and Zn levels in AAA and AOD tissue were similar to the levels in controls. The Zn:Cu ratio was significantly lower in the AAA tissue in comparison to both AOD and control tissue. In addition, AAA and AOD tissue had low ascorbic acid levels and low Cu,Zn-SOD activity with Cu,Zn-SOD:Mn-SOD ratios of 0.27 and 0.19, respectively, compared to a ratio of 3.20 in control aorta. These data indicate that aorta affected by aneurysms and occlusive disease have altered trace element and ascorbic acid concentrations, as well as low Cu,Zn-SOD activity. Although these observations do not directly support the hypothesis that AAA is associated with aortic Cu deficiency they do suggest a role for oxygen radicals or increased lipid peroxidation in occlusive and aneurysmal disease of the aorta.