Nanoanalytical analysis of bisphosphonate-driven alterations of microcalcifications using a 3D hydrogel system and in vivo mouse model.

Vascular calcification predicts atherosclerotic plaque rupture and cardiovascular events. Retrospective studies of women taking bisphosphonates (BiPs), a proposed therapy for vascular calcification, showed that BiPs paradoxically increased morbidity in patients with prior acute cardiovascular events but decreased mortality in event-free patients. Calcifying extracellular vesicles (EVs), released by cells within atherosclerotic plaques, aggregate and nucleate calcification. We hypothesized that BiPs block EV aggregation and modify existing mineral growth, potentially altering microcalcification morphology and the risk of plaque rupture. Three-dimensional (3D) collagen hydrogels incubated with calcifying EVs were used to mimic fibrous cap calcification in vitro, while an ApoE-/- mouse was used as a model of atherosclerosis in vivo. EV aggregation and formation of stress-inducing microcalcifications was imaged via scanning electron microscopy (SEM) and atomic force microscopy (AFM). In both models, BiP (ibandronate) treatment resulted in time-dependent changes in microcalcification size and mineral morphology, dependent on whether BiP treatment was initiated before or after the expected onset of microcalcification formation. Following BiP treatment at any time, microcalcifications formed in vitro were predicted to have an associated threefold decrease in fibrous cap tensile stress compared to untreated controls, estimated using finite element analysis (FEA). These findings support our hypothesis that BiPs alter EV-driven calcification. The study also confirmed that our 3D hydrogel is a viable platform to study EV-mediated mineral nucleation and evaluate potential therapies for cardiovascular calcification.

Hispanic Caregivers' experience of pediatric type 1 diabetes: A qualitative study.

OBJECTIVE: It is widely recognized that Type 1 Diabetes (T1D) outcomes are worse among Hispanic children; however, little is published about the perspectives of these patients and their caregivers. Our intent was to characterize the lived experience of Hispanic caregivers of children with T1D, focusing on the role of language and culture and their perspectives on current medical care and alternative care models. We studied Hispanic caregivers of patients (age 2-17 years) with T1D of greater than 6 months' duration. RESEARCH DESIGN AND METHODS: We completed semi-structured interviews and focus-groups of a purposive sample of 20 members of our population of interest. We developed a codebook and completed multidisciplinary consensus coding, then conducted iterative thematic analysis using qualitative software and discussion to generate themes. RESULTS: We gathered data from 20 Hispanic caregivers of T1D patients (11.37 ± 3.00 years old, 4.80 ± 2.84 years since diagnosis). 85% of caregivers were female, 80% preferred Spanish, and 15% were college-educated. Our analysis yielded 4 themes across the participants: (1) Culturally-based nutrition challenges, (2) Social isolation and lack of support for T1D care, (3) Hesitancy to fully embrace diabetes technology, and (4) Deferential views of care experience and providers. Overarching all of these themes was support for Hispanic group-based models of care tailored to address these concerns. CONCLUSIONS: The unique concerns among Hispanic caregivers of children with T1D suggest the importance of culturally tailored interventions to improve care. With successful implementation, such interventions could diminish widening disparities in healthcare outcomes.

Health Care Transition in Youth With Type 1 Diabetes and an A1C >9%: Qualitative Analysis of Pre-Transition Perspectives.

OBJECTIVE | To explore expectations for transition to adult care and experiences with transition planning among adolescents and young adults with type 1 diabetes and an A1C >9% at a tertiary care U.S. pediatric center. METHODS | We conducted semi-structured interviews in a purposive sample of patients 14-23 years of age who had had type 1 diabetes for at least 1 year and had an A1C >9%. A multidisciplinary team conducted iterative thematic analysis with deductive and inductive coding aided by NVivo software. RESULTS | Fourteen subjects participated (nine adolescents and five young adults, mean age 17.1 ± 3.2 years, 57% male, 79% Caucasian, 14% Hispanic, diabetes duration 8.2 ± 4.6 years, mean A1C 10.0 ± 0.8% for adolescents and 10.1 ± 0.7% for young adults). Qualitative analysis yielded four key themes. The first was lack of formal preparation; participants of all ages demonstrated a lack of preparation for transition and ignorance about the process, describing it as coming "out of the blue." The second was a desire for delayed and gradual transition; participants wanted to defer being "serious" about transition to a later/uncertain date, with a preference to "wait until I'm older" among all ages. Participants described ideal transition as a gradual process, taking place "a little at a time." The third was attachment to pediatric providers; participants demonstrated a nearly universal attachment to and "familiarity" with their pediatric diabetes care providers and expressed worries about an "uncomfortable" transition to adult providers. The fourth was concern about an impersonal adult care setting: participants perceived adult care as "formal," "scarier," and "tougher," with increased criticism about poor control; participants expressed fear that adult providers would not "know me" or appreciate "my diabetes journey." CONCLUSION | We demonstrated a lack of transition preparation and anxiety about transition and adult care among youth with type 1 diabetes and elevated A1C. Our results may help guide early, iterative pediatric transition counseling, with a special focus on addressing attachment and fears about adult diabetes care.

Genesis and growth of extracellular-vesicle-derived microcalcification in atherosclerotic plaques.

Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification areas. We also show that calcification morphology and the plaque's collagen content-two determinants of atherosclerotic plaque stability-are interlinked.

Breast density quantification using structured-light-based diffuse optical tomography simulations.

We present the feasibility of structured-light-based diffuse optical tomography (DOT) to quantify the breast density with an extensive simulation study. This study is performed on multiple numerical breast phantoms built from magnetic resonance imaging (MRI) images. These phantoms represent realistic tissue morphologies and are given typical breast optical properties. First, synthetic data are simulated at five wavelengths using our structured-light-based DOT forward problem. Afterwards, the inverse problem is solved to obtain the absorption images and subsequently the chromophore concentration maps. Parameters, such as segmented volumes and mean concentrations, are extracted from these maps and used in a regression model to estimate the percent breast densities. These estimations are correlated with the true values from MRI, r=0.97, showing that our new technique is promising in measuring breast density.

Zooming in on the genesis of atherosclerotic plaque microcalcifications.

Epidemiological evidence conclusively demonstrates that calcium burden is a significant predictor of cardiovascular morbidity and mortality; however, the underlying mechanisms remain largely unknown. These observations have challenged the previously held notion that calcification serves to stabilize the atherosclerotic plaque. Recent studies have shown that microcalcifications that form within the fibrous cap of the plaques lead to the accrual of plaque-destabilizing mechanical stress. Given the association between calcification morphology and cardiovascular outcomes, it is important to understand the mechanisms leading to calcific mineral deposition and growth from the earliest stages. We highlight the open questions in the field of cardiovascular calcification and include a review of the proposed mechanisms involved in extracellular vesicle-mediated mineral deposition.

Role of estrogen related receptor beta (ESRRB) in DFN35B hearing impairment and dental decay.

BACKGROUND: Congenital forms of hearing impairment can be caused by mutations in the estrogen related receptor beta (ESRRB) gene. Our initial linkage studies suggested the ESRRB locus is linked to high caries experience in humans. METHODS: We tested for association between the ESRRB locus and dental caries in 1,731 subjects, if ESRRB was expressed in whole saliva, if ESRRB was associated with the microhardness of the dental enamel, and if ESRRB was expressed during enamel development of mice. RESULTS: Two families with recessive ESRRB mutations and DFNB35 hearing impairment showed more extensive dental destruction by caries. Expression levels of ESRRB in whole saliva samples showed differences depending on sex and dental caries experience. CONCLUSIONS: The common etiology of dental caries and hearing impairment provides a venue to assist in the identification of individuals at risk to either condition and provides options for the development of new caries prevention strategies, if the associated ESRRB genetic variants are correlated with efficacy.

Autobiographical narratives can be used with confidence to collect information about ex-smokers' reasons for quitting smoking.

Although autobiographical narratives (ABNs) provide rich descriptions of how people change addictive behaviors, psychometric evaluations of such reports are rare. 27 ex-smokers who had quit for 1 to 5 years were interviewed twice about why they quit. Participants' ABN reasons for why they quit smoking were compared with their answers on the Reasons For Quitting (RFQ) scale and found to be similar. Ex-smokers' ABNs are reliably reported for number and types of reasons given for quitting. Reasons ex-smokers gave in their ABNs were similar to their RFQ subscale answers. ABNs, a qualitative measure of quitting smoking, captured more information about how people quit smoking than quantitative scales.

Leveraging Large Language Models to Analyze Continuous Glucose Monitoring Data: A Case Study.

Continuous glucose monitors (CGM) provide patients and clinicians with valuable insights about glycemic control that aid in diabetes management. The advent of large language models (LLMs), such as GPT-4, has enabled real-time text generation and summarization of medical data. Further, recent advancements have enabled the integration of data analysis features in chatbots, such that raw data can be uploaded and analyzed when prompted. Studying both the accuracy and suitability of LLM-derived data analysis performed on medical time series data, such as CGM data, is an important area of research. The objective of this study was to assess the strengths and limitations of using an LLM to analyze raw CGM data and produce summaries of 14 days of data for patients with type 1 diabetes. This study used simulated CGM data from 10 different cases. We first evaluated the ability of GPT-4 to compute quantitative metrics specific to diabetes found in an Ambulatory Glucose Profile (AGP). Then, using two independent clinician graders, we evaluated the accuracy, completeness, safety, and suitability of qualitative descriptions produced by GPT-4 across five different CGM analysis tasks. We demonstrated that GPT-4 performs well across measures of accuracy, completeness, and safety when producing summaries of CGM data across all tasks. These results highlight the capabilities of using an LLM to produce accurate and safe narrative summaries of medical time series data. We highlight several limitations of the work, including concerns related to how GPT-4 may misprioritize highlighting instances of hypoglycemia and hyperglycemia. Our work serves as a preliminary study on how generative language models can be integrated into diabetes care through CGM analysis, and more broadly, the potential to leverage LLMs for streamlined medical time series analysis.

[COVID-19 and the predominant groups of preventive behaviors and associated factors: semi-urban area]. / La COVID-19 y los grupos predominantes de conductas preventivas y factores asociados: zona semiurbana.

Background: Non-pharmacological interventions (NFI) or preventive actions (PA) are the best alternatives to control future pandemics, especially in vulnerable populations, such as semi-urban areas. Objective: To describe the predominant health behavior groups (HBG) and associated factors during the third wave of COVID-19 in a semi-urban area. Material and methods: A survey which included characteristics, factors related to COVID-19, perceptions of health behavior and PA was applied in a probabilistic sample in a first-level hospital in the State of Mexico. People of both sexes over 18 years of age were included. Using a hierarchical cluster analysis, HBGs were obtained and characterized with a descriptive and multivariate statistical analysis. Results: In a probabilistic sample (n = 260), 4 HBGs were identified: 2 of high-risk (HRG) and 2 of low-risk (LRG), and the proportions were 43.5% y 56.5%, respectively. The sociodemographic characteristics of both groups were similar. Perceptions of severity and COVID-19-related barriers significantly influenced health behaviors in LRG. In HRG, low security played a significant role, highlighting the importance of comorbidities as a clinical factor. Conclusions: In a semi-urban area, 2 crucial health behaviors were identified: one associated with low risk and the other with high risk. In the HRG, the perception of insecurity was particularly relevant, emphasizing the importance of comorbidities as a clinical factor.

Introducción: las intervenciones no farmacológicas (INF) o acciones preventivas (AP) contra enfermedades son la mejor alternativa para controlar futuras pandemias, en especial en poblaciones vulnerables, como las zonas semiurbanas. Objetivo: describir los grupos predominantes de conductas de salud (GCS) y los factores asociados durante la tercera ola de la COVID-19 en una zona semiurbana. Material y métodos: se aplicó una encuesta que incluyó las características, los factores relacionados con COVID-19, las percepciones de conductas de salud y las AP, en una muestra probabilística en un hospital de primer nivel del Estado de México. Se incluyeron personas de ambos sexos, mayores de 18 años. Mediante un análisis de conglomerados se caracterizaron los GCS con un análisis estadístico descriptivo y multivariado. Resultados: en una muestra probabilistica (n = 260), se identificaron cuatro GCS: 2 de riesgo alto de contagio por la COVID-19 (GRA) y 2 de riesgo bajo (GRB) y las proporciones fueron 43.5% y 56.5%, respectivamente. Las características sociodemográficas de los grupos fueron similares. Para los GRB los factores significativos fueron las percepciones sobre la severidad y las barreras relacionadas con la COVID-19. En los GRA fue la seguridad baja y destacó la importancia de la comorbilidad como factor clínico. Conclusiones: en una zona semiurbana se identificaron 2 conductas de salud de importancia: una de bajo riesgo y otra de alto riesgo. En el GRA, la percepción de seguridad baja fue especialmente relevante, lo cual resalta la importancia de las comorbilidades como factor clínico.

Role of TRAV locus in low caries experience.

Caries is the most common chronic, multifactorial disease in the world today; and little is still known about the genetic factors influencing susceptibility. Our previous genome-wide linkage scan has identified five loci related to caries susceptibility: 5q13.3, 13q31.1, 14q11.2, 14q 24.3, and Xq27. In the present study, we fine mapped the 14q11.2 locus to identify genetic contributors to caries susceptibility. Four hundred seventy-seven subjects from 72 pedigrees with similar cultural and behavioral habits and limited access to dental care living in the Philippines were studied. An additional 387 DNA samples from unrelated individuals were used to determine allele frequencies. For replication purposes, a total of 1,446 independent subjects from four different populations were analyzed based on their caries experience (low versus high). Forty-eight markers in 14q11.2 were genotyped using TaqMan chemistry. Transmission disequilibrium test was used to detect over transmission of alleles in the Filipino families, and Chi-square, Fisher's exact and logistic regression were used to test for association between low caries experience and variant alleles in the replication data sets. We finally assessed the mRNA expression of TRAV4 in the saliva of 143 study subjects. In the Filipino families, statistically significant associations were found between low caries experience and markers in TRAV4. We were able to replicate these results in the populations studied that were characteristically from underserved areas. Direct sequencing of 22 subjects carrying the associated alleles detects one missense mutation (Y30R) that is predicted to be probably damaging. Finally, we observed higher expression in children and teenagers with low caries experience, correlating with specific alleles in TRAV4. Our results suggest that TRAV4 may have a role in protecting against caries.

Using a clinical protocol for orthognathic surgery and assessing a 3-dimensional virtual approach: current therapy.

Oral and maxillofacial surgeons who perform orthognathic surgery face major changes in their practices, and these challenges will increase in the near future, because the extraordinary advances in technology applied to our profession are not only amazing but are becoming the standard of care as they promote improved outcomes for our patients. Orthognathic surgery is one of the favorite areas of practicing within the scope of practice of an oral and maxillofacial surgeon. Our own practice in orthognathic surgery has completed over 1,000 surgeries of this type. Success is directly related to the consistency and capability of the surgical-orthodontic team to achieve predictable, stable results, and our hypothesis is that a successful result is directly related to the way we take our records and perform diagnosis and treatment planning following basic general principles. Now that we have the opportunity to plan and treat 3-dimensional (3D) problems with 3D technology, we should enter into this new era with appropriate standards to ensure better results, instead of simply enjoying these new tools, which will clearly show not only us but everyone what we do when we perform orthognathic surgery. Appropriate principles need to be taken into account when implementing this new technology. In other words, new technology is welcome, but we do not have to reinvent the wheel. The purpose of this article is to review the current protocol that we use for orthognathic surgery and compare it with published protocols that incorporate new 3D and virtual technology. This report also describes our approach to this new technology.

Here for My Peer: The Future of First Responder Mental Health.

Workplace interventions that leverage social tactics to improve health and well-being are becoming more common. As an example, peer mental health support interventions aim to reduce stigma and promote treatment seeking in first responder populations. Given the social nature of these interventions, it is important to consider how the preexisting social context influences intervention outcomes. A peer mental health support intervention was delivered among first responders, and self-efficacy and intention to have supportive peer conversations were measured pre-and post-intervention. Trust in peers was measured prior to the intervention. Results suggest a floor effect may exist for self-efficacy, in which a foundational level of trust and pre-intervention self-efficacy may be needed to maximize intervention effectiveness. As the future of work brings complex safety and health challenges, collaborative solutions that engage multiple stakeholders (employees, their peers, and their organization) will be needed. This study suggests that more frequent attention to pre-existing intervention context, particularly social context in peer-focused intervention, will enhance intervention outcomes.

Effect of Antioxidants in the Treatment of COPD Patients: Scoping Review.

Chronic obstructive pulmonary disease (COPD) is a common, preventable, treatable lung disease characterized by persistent respiratory symptoms and airflow limitation and multiorgan impact. This affects the nutritional status of patients and requires multidimensional interventions including nutritional interventions according to individual metabolic needs. Our scoping review determined the effects of antioxidants in the treatment of COPD patients and their role in the decrease in the probability of exacerbations, hospital readmissions, and changes in lung function. The sources MEDLINE, LILACS, and Google Scholar were consulted and 19 studies were selected. The most indicated antioxidants are N-Acetylcysteine, vitamins E and D, and Zinc. Other antioxidants from plants or fruits extracts are also being investigated. The beneficial effect of antioxidants in stable or exacerbated patients is not clear, but theoretical and biological arguments of benefit justify lines of research that specify the impact on reducing oxidative stress and negative effects in COPD.

Beneficial effects of a multidomain cognitive rehabilitation program for traumatic brain injury-associated diffuse axonal injury: a case report.

BACKGROUND: Neuropsychological rehabilitation is a crucial component of medical care for patients with diffuse axonal injury (DAI). However, current cognitive intervention programs directed to favor the training of specific domains individually have shown controversial results. Here, we evaluated the effectiveness of a neuropsychological rehabilitation program directed to favor training of attention, memory, visuospatial abilities, and executive functioning together in a patient with severe traumatic brain injury (TBI)-associated DAI. CASE PRESENTATION: A 26-year-old Hispanic woman with a recent history of a severe TBI attended our center complaining of memory problems, dysarthria, and difficulty in planning. A comprehensive cognitive assessment revealed dysfunction in sustained, selective, and divided attention, alterations in memory, planning, and organization of executive behavior, as well as impairment of visuospatial cognitive functions. The patient underwent a 24-week neuropsychological rehabilitation program directed to favor attention, memory, visuospatial abilities, and executive functioning together. After the cognitive intervention, we observed a better patient's performance in tasks requiring sustained, selective, and divided attention, improvement of encoding and retrieval memory problems, use of spatial relationships, planning, and organization of behavior skills. We also observed generalization effects on other domains, such as learning, mental flexibility, inhibition functions, and language. CONCLUSIONS: In conclusion, our results suggest that neuropsychological rehabilitation programs favoring multiple domains together are useful in reestablishing cognitive deficits in patients with severe DAI.

Influenza vaccination rates among pharmacists.

OBJECTIVES: To quantify influenza vaccination rates and determine perceived barriers to influenza vaccination among U.S. pharmacists from various practice settings. DESIGN: Prospective study. SETTING: United States in 2008. PARTICIPANTS: 1,028 respondents, including 895 pharmacists. INTERVENTION: A survey request was distributed manually at the 2008 National Community Pharmacists Association annual meeting, and an initial e-mail was sent with two follow-up e-mails to all pharmacists who receive e-mails via Pharmacist e-link. MAIN OUTCOME MEASURES: Vaccination rates and barriers to vaccination among pharmacists. RESULTS: Pharmacists reported an influenza vaccination rate of 78%, with coverage varying across practice settings: hospital (88%), academia (86%), clinic (83%), and community (75%). Employers infrequently required the influenza vaccine as a condition of employment (7%), and slightly more than one-half (58%) compensated pharmacists for being vaccinated; both of these were significantly associated with higher influenza vaccination rates (P < 0.001 for both). One-quarter of pharmacists (26%) expressed at least one issue regarding the influenza vaccine. Pharmacists were significantly less likely to be vaccinated if they expressed a concern (91% vs. 43%, P < 0.0001). Community pharmacists were significantly less likely to be compensated for receiving the influenza vaccination and significantly more likely to express one or more concerns than pharmacists from any other practice setting. CONCLUSION: Pharmacists reported high influenza vaccination rates overall, with slight variability among practice settings. Although employers infrequently required influenza vaccination, approximately one-half of employers compensated their pharmacists for being vaccinated. Employer incentives and pharmacist attitudes were highly correlated with influenza vaccination.

A thermo-sensitive fluorescent agent based method for excitation light leakage rejection for fluorescence molecular tomography.

Fluorescence molecular tomography (FMT) is widely used in preclinical oncology research. FMT is the only imaging technique able to provide 3D distribution of fluorescent probes within thick highly scattering media. However, its integration into clinical medicine has been hampered by its low spatial resolution caused by the undetermined and ill-posed nature of its reconstruction algorithm. Another major factor degrading the quality of FMT images is the large backscattered excitation light component leaking through the rejection filters and coinciding with the weak fluorescent signal arising from a low tissue fluorescence concentration. In this paper, we present a new method based on the use of a novel thermo-sensitive fluorescence probe. In fact, the excitation light leakage is accurately estimated from a set of measurements performed at different temperatures and then is corrected for in the tomographic data. The obtained results show a considerable improvement in both spatial resolution and quantitative accuracy of FMT images due to the proper correction of fluorescent signals.

Cardiovascular calcification: current controversies and novel concepts.

Cardiovascular calcification is a commonly observed but incompletely understood mechanism of increased atherosclerotic plaque instability and accelerated aortic valve stenosis. Traditional histological staining and imaging techniques are nonspecific for the type of mineral present in calcified tissues, information that is critical for proper validation of in vitro and in vivo models. This review highlights current gaps in our understanding of the biophysical implications and the cellular mechanisms of valvular and vascular calcification and how they may differ between the two tissue types. We also address the hindrances of current cell culture systems, discussing novel platforms and important considerations for future studies of cardiovascular calcification.

Arboviral infections diagnosed in a European area colonized by Aedes albopictus (2009-2013, Catalonia, Spain).

BACKGROUND: The invasive mosquito Aedes albopictus, with proven vectorial ability to transmit European autochthonous cycles of dengue and chikungunya virus, has currently colonized every coastal department of Eastern Spain. The main objective of the study was to define the epidemiological and clinical characteristics as well as the trends of these two arboviral diseases in a European area heavily colonized by Ae. albopictus. METHOD: A voluntarily-based, prospective and multicenter surveillance study was performed in all medical units of the North Metropolitan area of Barcelona (406,000 inhabitants, Catalonia; Spain) with diagnostic capability from 2009 to 2013. Since any possible increase in arboviral cases could be justified by changes in traveling behaviors along the study period (especially longer trips) the trend showed by these two arboviral diseases was compared with that displayed by malaria cases during the same period. RESULTS: 38 out of 52 (73.1%) suspected cases could be serologically confirmed (IgM+): dengue 34/38 (89.5%) and chikungunya 4/38 (11.5%). No autochthonous cases were identified. The overall incidence of both arboviruses was 0.19 cases/10,000 inhabitants-year (95% CI: 0.07-0.3); dengue = 0.17 cases/10,000 inhabitants-year (95% CI: 0.05-0.3), and chikungunya = 0.02 cases/10,000 inhabitants-year (95% CI: 0.001-0.03). The Incidence Relative Risk of arboviral disease between 2009 and 2013 shown a significant trend (IRR = 1.27. IC 95%: 1.01-1.59; p = 0.043) when compared with that displayed by malaria (IRR = 1.04. IC 95%: 0.924-1.192). If no unexpected circumstances concur, the arboviral disease incidence tax would equal that of malaria about 2021-2022. CONCLUSIONS: The incidence of dengue and chikungunya is steadily increasing in the North Metropolitan area of Barcelona, a region densely colonized by Ae. albopictus, at the entire expense of imported cases (especially Visiting Friends and Relatives travelers). To date, no secondary autochthonous cases have been identified and, thus, they have not taken part in this rise.