Direct C-H electrophilic borylation with (C6F5)2B-NTf2 to generate B-N dibenzo[a,h]pyrenes.

The borylation of aryl substituted pyridines is an effective way of preparing B-N doped conjugated organic frameworks. Trihaloborane Lewis acids are often employed for this protocol, and may require further functionalization to replace the remaining halides on boron. We report a new, fully characterized, electrophilic borylating agent, (C6F5)2B(κ2-NTf2), that smoothly incorporates a -B(C6F5)2 unit into the model substrate 2-phenylpyridine. To demonstrate its utility in preparing more complex B-N doped structures, we use it to prepare seven examples of the 6a,13a-diaza-7,14-dibora-dibenzo[a,h]pyrene framework, with substituents of varying donor properties. The structural, redox, and photophysical properties of this new family of B-N doped polycyclic hydrocarbon compounds were probed experimentally and computationally.

Safety considerations for dietary supplement manufacturers in the United States.

Due to significant dietary supplement use in the US, product manufacturers must understand the importance of implementing a robust approach to establishing safety for all ingredients, including dietary ingredients, components, and finished dietary supplement products. Different regulatory pathways exist by which the safety of dietary ingredients can be established, and thus allowed to be marketed in a dietary supplement. For individual dietary ingredients, safety information may come from a variety of sources including history of safe use, presence of the ingredient in foods, and/or non-clinical and clinical data. On occasion safety data gaps are identified for a specific ingredient, particularly those of botanical origin. Modern toxicological methods and models can prove helpful in satisfying data gaps and are presented in this review. For finished dietary supplement products, issues potentially impacting safety to consider include claims, product labeling, overages, contaminants, residual solvents, heavy metals, packaging, and product stability. In addition, a safety assessment does not end once a product is marketed. It is important that manufacturers actively monitor and record the occurrence of adverse events reported in association with the use of their products, in accordance with the law. Herein, we provide a comprehensive overview of considerations for assessing dietary supplement safety.

Corrigendum: The cost of firearm violent crime in British Columbia, Canada.

[This corrects the article DOI: 10.3389/fpubh.2022.938091.].

Solution processed bismuth oxyiodide (BiOI) thin films and solar cells.

Post transition metal chalcohalides are an emerging class of semiconductor materials for optoelectronic applications. Within this class, bismuth oxyiodide (BiOI) is of particular interest due to its high environmental stability, low toxicity, and defect tolerance considered typical of 'ns2' materials. Here we fabricate BiOI thin films using a solution-processed method that affords pin-hole free highly pure films without any residual carbon or other contaminant species. Based on these films, solution processed all-inorganic solar cells with an architecture ITO/NiOx/BiOI/ZnO/Al are fabricated for the first time. Additional device improvements are realised by templating BiOI thin film growth to attain efficiencies that rival some of the best vacuum deposited devices. The BiOI thin films and devices outlined here are an excellent platform for the further development of solution processed bismuth chalcohalide optoelectronic devices.

Association of clinical prediction scores with hospital mortality in an adult medical and surgical intensive care unit in Kenya.

Importance: Mortality prediction among critically ill patients in resource limited settings is difficult. Identifying the best mortality prediction tool is important for counseling patients and families, benchmarking quality improvement efforts, and defining severity of illness for clinical research studies. Objective: Compare predictive capacity of the Modified Early Warning Score (MEWS), Universal Vital Assessment (UVA), Tropical Intensive Care Score (TropICS), Rwanda Mortality Probability Model (R-MPM), and quick Sequential Organ Failure Assessment (qSOFA) for hospital mortality among adults admitted to a medical-surgical intensive care unit (ICU) in rural Kenya. We performed a pre-planned subgroup analysis among ICU patients with suspected infection. Design setting and participants: Prospective single-center cohort study at a tertiary care, academic hospital in Kenya. All adults 18 years and older admitted to the ICU January 2018-June 2019 were included. Main outcomes and measures: The primary outcome was association of clinical prediction tool score with hospital mortality, as defined by area under the receiver operating characteristic curve (AUROC). Demographic, physiologic, laboratory, therapeutic, and mortality data were collected. 338 patients were included, none were excluded. Median age was 42 years (IQR 33-62) and 61% (n = 207) were male. Fifty-nine percent (n = 199) required mechanical ventilation and 35% (n = 118) received vasopressors upon ICU admission. Overall hospital mortality was 31% (n = 104). 323 patients had all component variables recorded for R-MPM, 261 for MEWS, and 253 for UVA. The AUROC was highest for MEWS (0.76), followed by R-MPM (0.75), qSOFA (0.70), and UVA (0.69) (p < 0.001). Predictive capacity was similar among patients with suspected infection. Conclusion and relevance: All tools had acceptable predictive capacity for hospital mortality, with variable observed availability of the component data. R-MPM and MEWS had high rates of variable availability as well as good AUROC, suggesting these tools may prove useful in low resource ICUs.

Demystifying the Relationship Between Metformin, AMPK, and Doxorubicin Cardiotoxicity.

Doxorubicin (DOX) is an extremely effective and wide-spectrum anticancer drug, but its long-term use can lead to heart failure, which presents a serious problem to millions of cancer survivors who have been treated with DOX. Thus, identifying agents that can reduce DOX cardiotoxicity and concurrently enhance its antitumor efficacy would be of great clinical value. In this respect, the classical antidiabetic drug metformin (MET) has stood out, appearing to have both antitumor and cardioprotective properties. MET is proposed to achieve these beneficial effects through the activation of AMP-activated protein kinase (AMPK), an essential regulator of mitochondrial homeostasis and energy metabolism. AMPK itself has been shown to protect the heart and modulate tumor growth under certain conditions. However, the role and mechanism of the hypothesized MET-AMPK axis in DOX cardiotoxicity and antitumor efficacy remain to be firmly established by in vivo studies using tumor-bearing animal models and large-scale prospective clinical trials. This review summarizes currently available literature for or against a role of AMPK in MET-mediated protection against DOX cardiotoxicity. It also highlights the emerging evidence suggesting distinct roles of the AMPK subunit isoforms in mediating the functions of unique AMPK holoenzymes composed of different combinations of isoforms. Moreover, the review provides a perspective regarding future studies that may help fully elucidate the relationship between MET, AMPK and DOX cardiotoxicity.

Social Threat Reduces Alcohol Consumption among College Students.

AIMS: Past research suggests that people report a greater desire to consume alcohol when they experience social threat-or threats to their social selves, such as social exclusion. Nevertheless, experimental research on the role of social threat in alcohol consumption is limited. The present study examined the causal relationship between social threat and wine consumption. METHODS: Undergraduate students (N = 83; Mage = 21.8 years old, SDage = 1.62 years old; 72.3% women; 61.4% Latinx/Hispanic) participated in a study under the pretense that they were in a focus group gauging students' opinions of a bar being constructed at their university. During the study, participants and two confederate researchers completed a group activity in which they selected design elements for the bar. Participants were randomly assigned to one of two conditions. In the social threat condition, confederates rejected participants' design choices and socially excluded them during a follow-up task. In the social acceptance condition, confederates supported participants' choices and did not socially exclude them. All participants then completed a wine taste test. RESULTS: Contrary to predictions, an independent-samples t-test revealed that participants who experienced social threat consumed significantly less wine than those who were socially accepted, t(81) = -2.22, P = 0.03, d = -0.49. Furthermore, a linear regression test revealed that this effect persisted even when controlling for typical alcohol-consumption behavior, b = 56.09, t = -2.50, P = 0.02, d = -0.61. CONCLUSION: The relationship between social threat and alcohol consumption may be more nuanced than anticipated. Discussion centers around two potential moderators including positive affect and identity.

An Open-Source Privacy-Preserving Large-Scale Mobile Framework for Cardiovascular Health Monitoring and Intervention Planning With an Urban African American Population of Young Adults: User-Centered Design Approach.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death worldwide and are increasingly affecting younger populations, particularly African Americans in the southern United States. Access to preventive and therapeutic services, biological factors, and social determinants of health (ie, structural racism, resource limitation, residential segregation, and discriminatory practices) all combine to exacerbate health inequities and their resultant disparities in morbidity and mortality. These factors manifest early in life and have been shown to impact health trajectories into adulthood. Early detection of and intervention in emerging risk offers the best hope for preventing race-based differences in adult diseases. However, young-adult populations are notoriously difficult to recruit and retain, often because of a lack of knowledge of personal risk and a low level of concern for long-term health outcomes. OBJECTIVE: This study aims to develop a system design for the MOYO mobile platform. Further, we seek to addresses the challenge of primordial prevention in a young, at-risk population (ie, Southern-urban African Americans). METHODS: Urban African Americans, aged 18 to 29 years (n=505), participated in a series of co-design sessions to develop MOYO prototypes (ie, HealthTech Events). During the sessions, participants were orientated to the issues of CVD risk health disparities and then tasked with wireframing prototype screens depicting app features that they considered desirable. All 297 prototype screens were subsequently analyzed using NVivo 12 (QSR International), a qualitative analysis software. Using the grounded theory approach, an open-coding method was applied to a subset of data, approximately 20% (5/25), or 5 complete prototypes, to identify the dominant themes among the prototypes. To ensure intercoder reliability, 2 research team members analyzed the same subset of data. RESULTS: Overall, 9 dominant design requirements emerged from the qualitative analysis: customization, incentive motivation, social engagement, awareness, education, or recommendations, behavior tracking, location services, access to health professionals, data user agreements, and health assessment. This led to the development of a cross-platform app through an agile design process to collect standardized health surveys, narratives, geolocated pollution, weather, food desert exposure data, physical activity, social networks, and physiology through point-of-care devices. A Health Insurance Portability and Accountability Act-compliant cloud infrastructure was developed to collect, process, and review data, as well as generate alerts to allow automated signal processing and machine learning on the data to produce critical alerts. Integration with wearables and electronic health records via fast health care interoperability resources was implemented. CONCLUSIONS: The MOYO mobile platform provides a comprehensive health and exposure monitoring system that allows for a broad range of compliance, from passive background monitoring to active self-reporting. These study findings support the notion that African Americans should be meaningfully involved in designing technologies that are developed to improve CVD outcomes in African American communities.

Exercise increases NPY/AgRP and TH neuron activity in the hypothalamus of female mice.

Recent evidence identifies a potent role for aerobic exercise to modulate the activity of hypothalamic neurons related to appetite; however, these studies have been primarily performed in male rodents. Since females have markedly different neuronal mechanisms regulating food intake, the current study aimed to determine the effects of acute treadmill exercise on hypothalamic neuron populations involved in regulating appetite in female mice. Mature, untrained female mice were exposed to acute sedentary, low- (10 m/min), moderate- (14 m/min), and high (18 m/min)-intensity treadmill exercise in a randomized crossover design. Mice were fasted 10 h before exercise, and food intake was monitored for 48 h after bouts. Immunohistochemical detection of cFOS was performed 3 h post-exercise to determine the changes in hypothalamic neuropeptide Y (NPY)/agouti-related peptide (AgRP), pro-opiomelanocortin (POMC), tyrosine hydroxylase (TH), and SIM1-expressing neuron activity concurrent with the changes in food intake. Additionally, stains for pSTAT3tyr705 and pERKthr202/tyr204 were performed to detect exercise-mediated changes in intracellular signaling. Briefly, moderate- and high-intensity exercises increased 24-h food intake by 5.9 and 19%, respectively, while low-intensity exercise had no effects. Furthermore, increases in NPY/AgRPARC, SIM1PVN, and TH neuron activity were observed 3 h after high-intensity exercise, with no effects on POMCARC neurons. While no effects of exercise on pERKthr202/tyr204 were observed, pSTAT3tyr705 was elevated specifically in NPY/AgRP neurons 3 h post-exercise. Overall, aerobic exercise increased the activity of several appetite-stimulating neuron populations in the hypothalamus of female mice, which may provide insight into previously reported sexual dimorphisms in post-exercise feeding.

Experiences of Physiotherapy Students, Health Care Providers, and Patients with a Role-Emerging Student Clinical Placement in an Emergency Department: A Qualitative Study.

Purpose: To understand the experiences and perspectives of physiotherapy (PT) students, their clinical instructor, nurses, physicians, and patients with a role-emerging student clinical placement in an emergency department (ED) and to identify barriers and facilitators in implementing this placement model. Method: We conducted qualitative semi-structured interviews with 6 PT students, 1 PT clinical instructor, 15 nurses, 12 physicians, and 17 patients. Five researchers independently coded the transcribed interviews and performed thematic analysis in an interpretive description tradition with frequent peer debriefing and reflexive discussions. Results: Students and their clinical instructor reported that the placement setting provided a unique learning opportunity. Patients and ED staff noted that involving the PT students in patient care delivery improved the musculoskeletal assessments and self-management advice provided to patients. Identified barriers included students' inability to chart in the electronic medical record, lack of bed space, and lack of clarity about students' scope and abilities. Reported facilitators included positive perceptions of the students' supervision and a perceived positive impact on patient care and the health care team. Conclusions: Participants reported positive experiences with the student ED placement and recommended similar placements in the future. Understanding barriers and facilitators in implementing PT student clinical placements in an ED can inform future placements.

Objectif : comprendre les expériences et les perspectives des étudiants en physiothérapie, de leur moniteur clinique, des infirmières, des médecins et des patients à l'égard d'un stage clinique émergent en physiothérapie à l'urgence et déterminer les obstacles et les incitatifs à l'adoption de ce modèle de stage. Méthodologie : entrevues qualitatives semi-structurées auprès de six étudiants en physiothérapie, un moniteur clinique en physiothérapie, 15 infirmières, 12 médecins et 17 patients. Cinq chercheurs ont codé la transcription des entrevues de manière indépendante et ont procédé à une analyse thématique dans la tradition de la description interprétative accompagnée de fréquents bilans avec les collègues et de fréquentes discussions réflexives. Résultats : selon les étudiants et leur moniteur clinique, le milieu de stage fournissait une occasion d'apprentissage unique. Les patients et le personnel de l'urgence ont remarqué que les étudiants amélioraient les évaluations musculosquelettiques et les conseils d'autoévaluation fournis aux patients. Les obstacles perçus étaient l'incapacité des étudiants à consigner l'information dans les dossiers médicaux électroniques, le manque de lits et le manque de clarté quant à la portée de pratiques et aux capacités des étudiants. Les incitatifs constatés incluaient les perceptions positives à l'égard de la supervision des étudiants et la perception de conséquences positives sur les soins pour les patients et l'équipe soignante. Conclusions : les participants ont fait état d'expériences positives dans le cadre des stages des étudiants à l'urgence et ont recommandé des stages semblables à l'avenir. Le fait de comprendre les obstacles et les incitatifs à la mise en œuvre de stages cliniques pour les physiothérapeutes à l'urgence pourra éclairer les futurs stages.

The cost of firearm violent crime in British Columbia, Canada.

Introduction: This study aimed to quantify the total cost of violent firearm-related offenses in British Columbia in 2016 Canadian dollars over a five-year period, 2012 to 2016. The purposes of this study were to estimate the direct costs to the health care system and indirect costs to society for violent firearm injuries and deaths; and to estimate criminal justice system costs pertaining to firearm incidents. Methods: Human and economic costs to the health care system and productivity losses were calculated using health administrative datasets such as B.C. Vital Statistics and Discharge Abstract Database. Criminal justice system costs pertaining to firearm incidents were estimated by applying weighted average costs to aggregate expenditures using methodology consistent with that used by Statistics Canada. Results: There was a total of 108 deaths and 245 hospitalizations resulting from violent firearm injuries. The total estimated cost of all violent firearm crime averaged $294,378,985 per year; human costs averaged $188,416,841 per year, where health care costs averaged $3,910,317 per year, productivity losses from workforce and household averaged $17,299,054 and $4,559,470 per year, respectively, and loss of life averaged $162,648,000; and $105,021,145 in criminal justice system costs, and $941,000 in programming costs. Conclusion: This study clearly demonstrates the significant cost of violent firearm injury in British Columbia and the impacts on the health care system, criminal justice system, and to society at large, particularly within the criminal justice system where the costs were significantly higher than health care.

Resting-State Functional Magnetic Resonance Imaging of Interhemispheric Functional Connectivity in Experimental Traumatic Brain Injury.

Although resting-state functional magnetic resonance imaging (rsfMRI) has the potential to offer insights into changes in functional connectivity networks after traumatic brain injury (TBI), there are few studies that examine the effects of moderate TBI for monitoring functional recovery in experimental TBI, and thus the neural correlates of brain recovery from moderate TBI remain incompletely understood. Non-invasive rsfMRI was used to longitudinally investigate changes in interhemispheric functional connectivity (IFC) after a moderate TBI to the unilateral sensorimotor cortex in rats (n = 9) up to 14 days. Independent component analysis of the rsfMRI data was performed. Correlations of rsfMRI sensorimotor networks were made with changes in behavioral scores, lesion volume, and T2- and diffusion-weighted images across time. TBI animals showed less localized rsfMRI patterns in the sensorimotor network compared to sham (n = 6) and normal (n = 5) animals. rsfMRI clusters in the sensorimotor network showed less bilateral symmetry compared to sham and normal animals, indicative of IFC disruption. With time after injury, many of the rsfMRI patterns in the sensorimotor network showed more bilateral symmetry, indicative of IFC recovery. The disrupted IFC in the sensorimotor and subsequent partial recovery showed a positive correlation with changes in behavioral scores. Overall, rsfMRI detected widespread disruption and subsequent recovery of IFC within the sensorimotor networks post-TBI, which correlated with behavioral changes. Therefore, rsfMRI offers the means to probe functional brain reorganization and thus has the potential to serve as an imaging marker to longitudinally stage TBI and monitor for novel treatments.

Energy Status Differentially Modifies Feeding Behavior and POMCARC Neuron Activity After Acute Treadmill Exercise in Untrained Mice.

Emerging evidence identifies a potent role for aerobic exercise to modulate activity of neurons involved in regulating appetite; however, these studies produce conflicting results. These discrepancies may be, in part, due to methodological differences, including differences in exercise intensity and pre-exercise energy status. Consequently, the current study utilized a translational, well-controlled, within-subject, treadmill exercise protocol to investigate the differential effects of energy status and exercise intensity on post-exercise feeding behavior and appetite-controlling neurons in the hypothalamus. Mature, untrained male mice were exposed to acute sedentary, low (10m/min), moderate (14m/min), and high (18m/min) intensity treadmill exercise in a randomized crossover design. Fed and 10-hour-fasted mice were used, and food intake was monitored 48h. post-exercise. Immunohistochemical detection of cFOS was performed 1-hour post-exercise to determine changes in hypothalamic NPY/AgRP, POMC, tyrosine hydroxylase, and SIM1-expressing neuron activity concurrent with changes in food intake. Additionally, stains for pSTAT3tyr705 and pERKthr202/tyr204 were performed to detect exercise-mediated changes in intracellular signaling. Results demonstrated that fasted high intensity exercise suppressed food intake compared to sedentary trials, which was concurrent with increased anorexigenic POMC neuron activity. Conversely, fed mice experienced augmented post-exercise food intake, with no effects on POMC neuron activity. Regardless of pre-exercise energy status, tyrosine hydroxylase and SIM1 neuron activity in the paraventricular nucleus was elevated, as well as NPY/AgRP neuron activity in the arcuate nucleus. Notably, these neuronal changes were independent from changes in pSTAT3tyr705 and pERKthr202/tyr204 signaling. Overall, these results suggest fasted high intensity exercise may be beneficial for suppressing food intake, possibly due to hypothalamic POMC neuron excitation. Furthermore, this study identifies a novel role for pre-exercise energy status to differentially modify post-exercise feeding behavior and hypothalamic neuron activity, which may explain the inconsistent results from studies investigating exercise as a weight loss intervention.

Machine learning classification of texture features of MRI breast tumor and peri-tumor of combined pre- and early treatment predicts pathologic complete response.

PURPOSE: This study used machine learning classification of texture features from MRI of breast tumor and peri-tumor at multiple treatment time points in conjunction with molecular subtypes to predict eventual pathological complete response (PCR) to neoadjuvant chemotherapy. MATERIALS AND METHOD: This study employed a subset of patients (N = 166) with PCR data from the I-SPY-1 TRIAL (2002-2006). This cohort consisted of patients with stage 2 or 3 breast cancer that underwent anthracycline-cyclophosphamide and taxane treatment. Magnetic resonance imaging (MRI) was acquired pre-neoadjuvant chemotherapy, early, and mid-treatment. Texture features were extracted from post-contrast-enhanced MRI, pre- and post-contrast subtraction images, and with morphological dilation to include peri-tumoral tissue. Molecular subtypes and Ki67 were also included in the prediction model. Performance of classification models used the receiver operating characteristics curve analysis including area under the curve (AUC). Statistical analysis was done using unpaired two-tailed t-tests. RESULTS: Molecular subtypes alone yielded moderate prediction performance of PCR (AUC = 0.82, p = 0.07). Pre-, early, and mid-treatment data alone yielded moderate performance (AUC = 0.88, 0.72, and 0.78, p = 0.03, 0.13, 0.44, respectively). The combined pre- and early treatment data markedly improved performance (AUC = 0.96, p = 0.0003). Addition of molecular subtypes improved performance slightly for individual time points but substantially for the combined pre- and early treatment (AUC = 0.98, p = 0.0003). The optimal morphological dilation was 3-5 pixels. Subtraction of post- and pre-contrast MRI further improved performance (AUC = 0.98, p = 0.00003). Finally, among the machine-learning algorithms evaluated, the RUSBoosted Tree machine-learning method yielded the highest performance. CONCLUSION: AI-classification of texture features from MRI of breast tumor at multiple treatment time points accurately predicts eventual PCR. Longitudinal changes in texture features and peri-tumoral features further improve PCR prediction performance. Accurate assessment of treatment efficacy early on could minimize unnecessary toxic chemotherapy and enable mid-treatment modification for patients to achieve better clinical outcomes.

Polymer particles for the intra-articular delivery of drugs to treat osteoarthritis.

Osteoarthritis (OA) is a leading cause of chronic disability. It is a progressive disease, involving pathological changes to the entire joint, resulting in joint pain, stiffness, swelling, and loss of mobility. There is currently no disease-modifying pharmaceutical treatment for OA, and the treatments that do exist suffer from significant side effects. An increasing understanding of the molecular pathways involved in OA is leading to many potential drug targets. However, both current and new therapies can benefit from a targeted approach that delivers drugs selectively to joints at therapeutic concentrations, while limiting systemic exposure to the drugs. Delivery systems including hydrogels, liposomes, and various types of particles have been explored for intra-articular drug delivery. This review will describe progress over the past several years in the development of polymer-based particles for OA treatment, as well as theirin vitro, in vivo, and clinical evaluation. Systems based on biopolymers such as polysaccharides and polypeptides, as well as synthetic polyesters, poly(ester amide)s, thermoresponsive polymers, poly(vinyl alcohol), amphiphilic polymers, and dendrimers will be described. We will discuss the role of particle size, biodegradability, and mechanical properties in the behavior of the particles in the joint, and the challenges to be addressed in future research.

Symptomatic, functional and service utilization outcomes of migrants with a first episode of psychosis.

BACKGROUND: Certain migrant groups have been identified as being at increased risk of developing a psychotic disorder, but there is limited research on the outcomes for migrants who develop a first episode of psychosis (FEP). We investigated symptomatic outcomes (remission and relapse rates), functional outcomes (occupational status and relationships) and service utilization (hospital admission and engagement). METHODS: Young people, aged between 15 and 24, who presented with FEP to the Early Psychosis Prevention and Intervention Centre (EPPIC) at Orygen between 01.01.11 and 31.12.16 were included. Place of birth was recorded at the time of presentation. To determine remission, symptoms were scored at three-month intervals using the short-form Scale for the Assessment of Positive Symptoms. RESULTS: A total of 1220 young people presented with FEP over the six-year period (mean age = 19.6 ± 2.8). Of these, 58.1% were male and 24.0% were first-generation migrants. While there was no difference in overall rates of admission after presentation, migrants were more likely to have an involuntary admission after presentation (31.4% vs. 24.6%, aHR = 1.54, 95% CI [1.19, 2.01]) and this risk was greatest for African migrants (HR = 1.98, 95% C.I. [1.37, 2.86]. The rates of remission and relapse were similar in migrants and those born in Australia and there was no difference in functional outcomes, such as employment rates at follow-up. DISCUSSION: The outcomes for migrants who experience FEP appear to be largely similar to those for the Australian-born population. Our finding that a greater rate of involuntary admission for migrants at presentation supports existing literature and needs further exploration to improve clinical care.