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BACKGROUND/OBJECTIVE: Slowing the progression of diabetic kidney disease (DKD) is critical. We conducted a randomized controlled trial to target risk factors for DKD progression. METHODS: We evaluated the effect of a pharmacist-led intervention focused on supporting healthy behaviors, medication management, and self-monitoring on decline in estimated glomerular filtration rate (eGFR) for 36 months compared with an educational control. RESULTS: We randomized 138 individuals to the intervention group and 143 to control. At baseline, mean (SD) eGFR was 80.7 (21.7) mL/min/1.73m2, 56% of participants had chronic kidney disease and a history of uncontrolled hypertension with a baseline SBP of 134.3 mm Hg. The mean (SD) decline in eGFR by cystatin C from baseline to 36 months was 5.0 (19.6) and 5.9 (18.6) mL/min/1.73m2 for the control and intervention groups, respectively, with no significant between-group difference (P=0.75). CONCLUSIONS: We did not observe a significant difference in clinical outcomes by study arm. However, we showed that individuals with DKD will engage in a pharmacist-led intervention. The potential explanations for a lack of change in DKD risk factors can be attributed to 5 broad issues, challenges: (1) associated with enrolling patients with low eGFR and poor BP control; (2) implementing the intervention; (3) limited duration during which to observe any clinical benefit from the intervention; (4) potential co-intervention or contamination; and (5) low statistical power.
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OBJECTIVES: This paper outlines the experience developing Addiction Medicine Practice-Based Research Network (AMNet), which promotes the adoption of patient-reported outcome measures (PROMs) and measurement-based care in outpatient addiction treatment practices and creates a platform for quality improvement and research. METHODS: From August 2019 to July 2023, the AMNet team selected patient-reported outcome measures for implementation in the American Psychiatric Association's clinical data registry (PsychPRO), recruited addiction medicine providers, and collected PROMs data. RESULTS: AMNet selected 12 PROMs for implementation in PsychPRO. Through July 2023, 1565 providers expressed interest, of whom 216 of the 929 eligible providers (23%) attended an onboarding call/webinar. Two hundred six providers (95%) from 54 practices returned Participation Agreements. Subsequently, 65 providers (32%) from 39 practices withdrew, resulting in 141 (68%) providers from 15 practices. From November 2020 to July 2023, 38 providers submitted PROMs data using 1 of 3 PsychPRO patient portals. Sixteen of the 53 providers (30%) who signed up for the initial portal collected data from 468 patients. As of July 2023, 83 of the 141 providers (59%) opted to submit PROMs data from their own portal or electronic health record. CONCLUSIONS: Next steps will include continued recruitment of providers, addressing barriers to data transfer and integrating data from providers' portals into the registry to create a platform for future research.
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Background: Oral cancer is a significant global health concern with substantial morbidity and mortality rates. Early detection during routine dental check-ups is crucial for improved patient outcomes. Dental professionals play a pivotal role in conducting oral cancer screenings, but the frequency and methods they employ remain understudied. Aim: This cross-sectional study aimed to investigate the frequency of oral cancer screenings during routine dental check-ups conducted by dental professionals and the methods they commonly use. Materials and Methods: A survey was administered to 500 dental professionals, including dentists and dental hygienists, representing diverse demographics and practice settings. The survey collected data on the frequency of oral cancer screenings and the primary methods employed. Descriptive statistics and Chi-square tests were used for data analysis. Results: The study found that 85% of dental professionals conduct oral cancer screenings during routine dental check-ups, with 48% performing them annually and 33% at every visit. Visual inspection (97%) and palpation (83%) were the most commonly used methods, while adjunctive screening tools (45%) were less frequently incorporated. Conclusion: Dental professionals are actively engaged in oral cancer screenings during routine dental check-ups, demonstrating a commitment to early detection. Visual inspection and palpation are commonly employed methods, but there is room for improvement in the adoption of adjunctive screening tools.
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Mini-screws, also known as temporary anchorage devices (TADs), offer enhanced control and versatility in orthodontic treatment by providing stable anchorage points. This clinical study aims to evaluate the effectiveness of mini-screw-supported molar intrusion in orthodontic practice. For this clinical study, a cohort of 40 orthodontic patients with various malocclusions requiring molar intrusion as part of their treatment plan was recruited. The age range of the participants spanned from 14 to 35 years, representing a diverse patient population. The intervention involved the implementation of mini-screw-supported molar intrusion on one side of the maxillary arch in each patient. To achieve this, temporary mini-screws were strategically placed, and a combination of orthodontic forces and mini-screw anchorage was employed to intrude the molars. The primary outcome measure for this study was the amount of molar intrusion achieved, which was quantified in millimeters from the initial evaluation to the final visit. Additionally, the duration of treatment required to achieve the desired molar intrusion was recorded in months. The results of this clinical study demonstrated that mini-screw-supported molar intrusion was an effective and safe orthodontic technique. On average, a significant mean molar intrusion amount of 4.8 mm (standard deviation [SD] ± 0.6) was achieved with the mini-screw-supported approach. Furthermore, the treatment duration required to attain the desired molar intrusion was relatively short, with a mean of 6.2 months (SD ± 1.1). In conclusion, this clinical study provides evidence that mini-screw-supported molar intrusion is an effective and safe approach in orthodontic practice. It offers orthodontists the advantage of enhanced control and predictability in molar intrusion procedures.
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Background: The mixed dentition stage in children is a critical period for orthodontic assessment and intervention. This study investigates the effects of interceptive orthodontics on dental and skeletal development in children with mixed dentition, aiming to evaluate the potential benefits of early orthodontic treatment. Materials and Methods: A retrospective analysis was conducted on a cohort of 150 children with mixed dentition (aged 7-11 years), who received interceptive orthodontic treatment. Dental and skeletal records, including cephalometric radiographs and dental cast models, were collected before and after treatment. A control group of 150 untreated children with mixed dentition was also assessed for comparison. Various dental and skeletal parameters, such as dental alignment, overjet (OJ), overbite (OB), and cephalometric measurements, were recorded and analyzed. Results: The results of this study indicate significant improvements in dental alignment and occlusion in the group of children who received interceptive orthodontic treatment. The average reduction in OJ was 3.5 mm, and the OB correction averaged 2.1 mm. Cephalometric analysis showed positive changes in skeletal relationships, with a mean reduction in the angle formed by point A, nasion (N) and point B. (ANB) angle of 2.8 degrees. These improvements were statistically significant compared to the control group (P < 0.05). Conclusion: Early orthodontic intervention, such as interceptive orthodontics, has a positive impact on dental and skeletal development in children with mixed dentition.
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Fisetin (FST), a natural flavonoid compound derived from various fruits and vegetables, including apple, strawberry, and onion, demonstrates potential for a wide range of pharmaceutical applications, including potential anticancer properties. However, challenges such as low bioavailability, poor aqueous solubility, and limited permeability restrict the use of FST in the pharmaceutical sector. Nowadays, targeted nanomedicines have garnered attention to overcome limitations associated with phytochemicals, including FST. In the present study, we have designed and successfully prepared folate-targeted FST nanoparticles (FFNPs). Characterization through DLS and FE-SEM revealed the successful preparation of monodisperse (PDI: 0.117), nanoscale-sized (150 nm), and spherical nanoparticles. Physicochemical characterization including FTIR, XRD, DSC, and TGA analysis, confirmed the encapsulation of the FST within the Folic acid (FA) - conjugated nanoparticles (CNPs) and revealed its amorphous nature. Molecular docking analysis revealed the strong binding affinity and specific amino acid interactions involved in the BSA-FST-FA complex, suggesting the potential synergistic effect of FST and FA in enhancing the therapeutic activity of the FFANPs. Cytotoxic assessments by the MTT assay, migration assay, AO-EtBr staining assay, colony formation assay, and cellular uptake study demonstrated enhanced anticancer efficacy, apoptosis induction, and enhanced uptake of FFNPs compared to pure FST. These findings propose prepared FFNPs as a promising targeted drug delivery nanocarrier for effective FST delivery in cancer therapy.
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OBJECTIVE: The authors investigated adaptations to outpatient care delivery and changes in treatment demand and engagement among patients receiving medications for opioid use disorder (MOUD) in the months after the declaration of the COVID-19 public health emergency in 2020. METHODS: Data were collected through an online survey (June-November 2020) of outpatient MOUD prescribers. The survey obtained information on outpatient practices' adaptations to MOUD treatment and urine drug screening (UDS) and elicited provider views on the effects of the COVID-19 pandemic on patient demand for, and engagement in, treatment. Multivariable regression analyses were used to examine associations among practice characteristics, patient engagement, and service adaptations. RESULTS: Of 516 respondents, 74% reported adaptations to MOUD delivery during the pandemic. Most respondents implemented virtual visits for initial (67%) and follow-up (77%) contacts. Prescribers of buprenorphine were more likely than those who did not prescribe the medication to report MOUD adaptations. Among respondents reporting any MOUD adaptation, 77% made adaptations to their UDS practices. Among 513 respondents who answered COVID-19-related questions, 89% reported that the pandemic had affected the treatment and engagement of their patients. Of these respondents, 30% reported increased difficulty with patient engagement, and 45% reported that their patients preferred virtual visits during this period, whereas 18% endorsed patient preference for in-person visits. CONCLUSIONS: Telehealth and federal regulatory easements in response to the COVID-19 pandemic enabled providers to continue treating patients for opioid use disorder in 2020. The results suggest that care adaptations and changes in patient demand and engagement were common in the practices surveyed.
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COVID-19 , Trastornos Relacionados con Opioides , Humanos , Pandemias , Participación del Paciente , Atención Ambulatoria , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/epidemiologíaRESUMEN
Stimulator of interferon genes (STING) is a dimeric transmembrane adapter protein that plays a key role in the human innate immune response to infection and has been therapeutically exploited for its antitumor activity. The activation of STING requires its high-order oligomerization, which could be induced by binding of the endogenous ligand, cGAMP, to the cytosolic ligand-binding domain. Here we report the discovery through functional screens of a class of compounds, named NVS-STGs, that activate human STING. Our cryo-EM structures show that NVS-STG2 induces the high-order oligomerization of human STING by binding to a pocket between the transmembrane domains of the neighboring STING dimers, effectively acting as a molecular glue. Our functional assays showed that NVS-STG2 could elicit potent STING-mediated immune responses in cells and antitumor activities in animal models.
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Proteínas Adaptadoras Transductoras de Señales , Proteínas de la Membrana , Animales , Humanos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Bioensayo , Citosol , Inmunidad Innata , Ligandos , Proteínas de la Membrana/metabolismoRESUMEN
Target spot caused by Corynespora cassiicola is a problematic disease in tropical and subtropical soybean (Glycine max) growing regions. Although resistant soybean genotypes have been identified, the genetic mechanisms underlying target spot resistance has not yet been studied. To address this knowledge gap, this is the first genome-wide association study (GWAS) conducted using the SoySNP50K array on a panel of 246 soybean accessions, aiming to unravel the genetic architecture of resistance. The results revealed significant associations of 14 and 33 loci with resistance to LIM01 and SSTA C. cassiicola isolates, respectively, with six loci demonstrating consistent associations across both isolates. To identify potential candidate genes within GWAS-identified loci, dynamic transcriptome profiling was conducted through RNA-Seq analysis. The analysis involved comparing gene expression patterns between resistant and susceptible genotypes, utilizing leaf tissue collected at different time points after inoculation. Integrating results of GWAS and RNA-Seq analyses identified 238 differentially expressed genes within a 200 kb region encompassing significant quantitative trait loci (QTLs) for disease severity ratings. These genes were involved in defense response to pathogen, innate immune response, chitinase activity, histone H3-K9 methylation, salicylic acid mediated signaling pathway, kinase activity, and biosynthesis of flavonoid, jasmonic acid, phenylpropanoid, and wax. In addition, when combining results from this study with previous GWAS research, 11 colocalized regions associated with disease resistance were identified for biotic and abiotic stress. This finding provides valuable insight into the genetic resources that can be harnessed for future breeding programs aiming to enhance soybean resistance against target spot and other diseases simultaneously.
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The synthesis, characterization, and antibacterial and antioxidant activity of thiadiazole-deoxycholic/lithocholic acid conjugates are described in this communication. The structures of the synthesised bile acid-thiadiazole conjugates were studied using 1H NMR, 13C NMR and FTIR. Compounds 4c (IC50; 15.34 ± 0.07 µM) and 5c (IC50; 13.45 ± 0.25 µM) demonstrated greater antioxidant activity than the reference compound ascorbic acid (IC50; 20.72 ± 1.02 µM) in DPPH assay. The most effective conjugates against P. vulgarise were 4c (IC50; 24 ± 2.3 µM), 4 g (IC50; 29 ± 2.5 µM), and 5c (IC50; 93 ± 3.6 µM), whereas the most effective conjugates against E. coli were 4e (IC50; 55 ± 2.1 µM) and 4f (IC50; 52 ± 3.5 µM). Conjugates 4c and 5c were the most effective against B. megaterium of all the synthesised conjugates, with IC50 values of 15 ± 1.08 and 20 ± 1.1 µM, respectively. Thus, a large library of compounds derived from bile acid can be easily synthesised for extensive structure-activity relationship studies in order to identify the most appropriate antibacterial agents and antioxidant activity.
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Antineoplásicos , Tiadiazoles , Antioxidantes/química , Tiadiazoles/farmacología , Tiadiazoles/química , Ácidos y Sales Biliares/farmacología , Escherichia coli , Antibacterianos/química , Relación Estructura-Actividad , Estructura Molecular , Antineoplásicos/farmacologíaRESUMEN
Target spot is caused by Corynespora cassiicola, which heavily affects soybean production areas that are hot and humid. Resistant soybean genotypes have been identified; however, the molecular mechanisms governing resistance to infection are unknown. Comparative transcriptomic profiling using two known resistant genotypes and two susceptible genotypes was performed under infected and control conditions to understand the regulatory network operating between soybean and C. cassiicola. RNA-Seq analysis identified a total of 2571 differentially expressed genes (DEGs) which were shared by all four genotypes. These DEGs are related to secondary metabolites, immune response, defense response, phenylpropanoid, and flavonoid/isoflavonoid pathways in all four genotypes after C. cassiicola infection. In the two resistant genotypes, additional upregulated DEGs were identified affiliated with the defense network: flavonoids, jasmonic acid, salicylic acid, and brassinosteroids. Further analysis led to the identification of differentially expressed transcription factors, immune receptors, and defense genes with a leucine-rich repeat domain, dirigent proteins, and cysteine (C)-rich receptor-like kinases. These results will provide insight into molecular mechanisms of soybean resistance to C. cassiicola infection and valuable resources to potentially pyramid quantitative resistance loci for improving soybean germplasm.
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Ascomicetos , Glycine max , Glycine max/metabolismo , Perfilación de la Expresión Génica , Ascomicetos/genética , Transcriptoma , Enfermedades de las Plantas/genéticaRESUMEN
Background: Although the effects of maternal behavior on the development of child emotion characteristics is relatively well-established, effects of infant characteristics on maternal emotion development is less well known. This gap in knowledge persists despite repeated calls for including child-to-mother effects in studies of emotion. We tested the theory-based postulate that infant temperamental negativity moderates longitudinal trajectories of mothers' perinatal symptoms of anxiety and depression. Method: Participants were 92 pregnant community women who enrolled in a longitudinal study of maternal mental health; symptoms of anxiety and depression were assessed during the second and third trimesters of pregnancy and again at infant age 4 months. A multimethod assessment of infants' temperament-based negative reactivity was conducted at infant age 4 months. Results: Maternal symptoms of anxiety showed smaller postnatal declines when levels of infant negativity were high. Negative reactivity, assessed via maternal report of infant behavior, was related to smaller postnatal declines in maternal anxiety, while infant negative reactivity, at the level of neuroendocrine function, was largely unrelated to longitudinal changes in maternal anxiety symptoms. Infant negativity was related to early levels, but largely unrelated to trajectories of maternal symptoms of depression. Limitations: Limitations of this work include a relatively small and low-risk sample size, the inability to isolate environmental effects, and a nonexperimental design that precludes causal inference. Conclusions: Findings suggest that levels of infant negativity are associated with differences in the degree of change in maternal anxiety symptoms across the perinatal period.
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Despite widespread acceptance that prenatal symptoms of depression in mothers are detrimental to infants' long-term emotional and cognitive development, little is known about the mechanisms that may integrate outcomes across these domains. Rooted in the integrative perspective that emotional development is grounded in developing cognitive processes, we hypothesized that prenatal symptoms of depression in mothers would be associated with delays in neural maturation that support sociocognitive function in infants, leading to more problematic behaviors. We used a prospective longitudinal study of mothers (N = 92) and their infants to test whether self-reported symptoms of depression in mothers during the second and third trimesters were associated with neural development and infant outcomes at 4 months of age. While controlling for postpartum symptoms of depression, more prenatal symptoms of depression in mothers predicted less neural maturation in the parietal region of 4-month-old infants. Less neural maturation, in turn, was associated with greater infant negativity, suggesting neural maturation as a putative mechanism linking maternal symptoms of depression with infant outcomes. Differences in neural regions and developmental timing are also discussed.
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Depresión Posparto , Depresión , Femenino , Embarazo , Lactante , Humanos , Depresión/psicología , Estudios Prospectivos , Estudios Longitudinales , Emociones , Madres/psicología , Depresión Posparto/psicologíaRESUMEN
Children from lower socioeconomic status (SES) families are at increased risk for anxiety problems, though knowledge of the pathways by which SES predicts children's anxiety outcomes remains scant. Limited work suggests SES as a moderator of links between early development and anxiety outcomes but has not used a longitudinal framework or a multimethod approach. In this preregistered study, SES was tested as a simultaneous moderator of putatively biologically (error-related negativity [ERN]) and contextually (authoritarian parenting) based pathways of anxiety risk from ages 3 (Mage = 3.59), 4 (Mage = 4.57), and 5 (Mage = 5.52) [N = 121; 59% female]. Families were largely White and Non-Hispanic and reported a broad range of income (less than $15,000 to $90,001 or greater) from 2014 to 2017. We hypothesized that putatively biological pathways would be the strongest predictors of child outcomes at high SES and that putatively contextual pathways would be the strongest predictors of child outcomes at low SES. Consistent with expectations, smaller ERN across ages 3 and 4 was associated with greater anxious behaviors at age 5, but only at high SES. SES did not moderate parenting-based pathways of risk. Results are partially consistent with previous work suggesting that putatively biological pathways are more robust predictors of child outcomes at high SES than at low SES. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Trastornos de la Conducta Infantil , Clase Social , Niño , Humanos , Femenino , Preescolar , Masculino , Responsabilidad Parental , Ansiedad , Trastornos de AnsiedadRESUMEN
INTRODUCTION: Flibanserin treatment increases sexual desire and satisfying sexual events while decreasing distress in certain women diagnosed with acquired, generalized hypoactive sexual desire disorder (HSDD). Additional aspects of sexual function and the time course of response have not been fully characterized. AIM: To evaluate changes in sexual function assessed by the subdomains of the Female Sexual Function Index (FSFI) in women with HSDD treated with flibanserin. METHODS: FSFI data pooled from 3 pivotal flibanserin trials in premenopausal women (flibanserin = 1,165; placebo = 1,203) and FSFI data from one complete flibanserin trial in postmenopausal women (flibanserin = 432; placebo = 463) were subjected to post-hoc analyses. For each FSFI subdomain, least squares mean change from baseline was calculated at each assessment visit (treatment weeks 4, 8, 16, 24) and treatment groups were compared using analysis of covariance. Standardized effect size (Cohen's d) was also determined for each FSFI subdomain. MAIN OUTCOME MEASURE: Changes from baseline in FSFI subdomains. RESULTS: Compared to placebo, both premenopausal (P < .02) and postmenopausal (P < .045) patients in the flibanserin group reported significantly greater increases over baseline in the FSFI subdomain scores of desire, arousal, lubrication, orgasm, and satisfaction. In premenopausal patients, significant improvements were observed at the first assessment of response (week 4) and were maintained through week 24. In postmenopausal patients, significant improvements were observed at week 4 for desire and arousal, while significant improvements in lubrication, orgasm, and satisfaction were observed at week 8. At week 24, excluding the pain subdomain, standardized effect sizes ranged from 0.18 to 0.28 in the premenopausal cohort and 0.12 to 0.29 in the postmenopausal cohort. In both pre- and postmenopausal patients, improvements in pain were smaller and largely undifferentiated between treatment groups. CLINICAL IMPLICATIONS: While variations in time to response should be taken into consideration, on average, the beneficial impact of flibanserin on overall sexual function occurs within the first month of treatment. The data also suggest that the response to flibanserin is sustained for the duration of treatment. STRENGTHS AND LIMITATIONS: Sexual function assessments were performed in a large cohort of 2,368 premenopausal women and 895 postmenopausal women. However, the FSFI assesses changes over a 1-month period and time points earlier than 4 weeks could not be assessed. CONCLUSION: These analyses suggest that assessment of benefit of flibanserin in HSDD should include improvements across all domains of sexual function, not only desire. Simon JA, Clayton AH, Goldstein I, et al. Effects of Flibanserin on Subdomain Scores of the Female Sexual Function Index in Women With Hypoactive Sexual Desire Disorder. Sex Med 2022;10:100570.
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Multisystem Inflammatory Syndrome in Children (MIS-C), a rare condition, has been reported approximately 2-4 weeks after the onset of COVID-19 in children and adolescents, causing inflammation in multiple systems, including cardiovascular and respiratory, digestive, and central nervous systems. This condition is also known as hyperinflammatory shock, Kawasaki-like disease, and Pediatric Inflammatory Multisystem Syndrome (PIMS). The signs and symptoms include but are not limited to fever, rash, peripheral edema, gastrointestinal symptoms, conjunctivitis, and shock. Thirty-eight studies met our criteria, with a total of 5822 patients. The most affected population was between 5-18 years of age. We noted that MIS-C presented with a wide range of signs and symptoms that overlap with Kawasaki Disease, including high fever, sore throat, malaise, tachypnea, tachycardia, conjunctival injection, mucosal edema, cardiac involvement, and gastrointestinal symptoms. It causes an increase in IL-17A, IL-6, and arterial damage, a distinct difference from Kawasaki disease. The laboratory findings in MIS-C showed an increase in inflammatory markers like CRP, ESR, ferritin, leukocytes, and TNF-α. WHO stated that 23% of affected children with MIS-C had underlying conditions like chronic lung diseases, cardiovascular disease, and immunosuppression. In most affected children, aspirin and IVIG were successful, which resulted in a decrease in the inflammatory markers. We find that MIS-C is a rare, but potentially fatal pediatric complication, after COVID-19 infection. The aim of this article is to study the emerging relationship between COVID-19 and MIS-C in children and adolescents affected by this condition, to discuss the immunological mechanisms, and explore potential therapies.
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The mechanistic details of the tethered agonist mode of activation for the adhesion GPCR ADGRF5/GPR116 have not been completely deciphered. We set out to investigate the physiological importance of autocatalytic cleavage upstream of the agonistic peptide sequence, an event necessary for NTF displacement and subsequent receptor activation. To examine this hypothesis, we characterized tethered agonist-mediated activation of GPR116 in vitro and in vivo. A knock-in mouse expressing a non-cleavable GPR116 mutant phenocopies the pulmonary phenotype of GPR116 knock-out mice, demonstrating that tethered agonist-mediated receptor activation is indispensable for function in vivo. Using site-directed mutagenesis and species-swapping approaches, we identified key conserved amino acids for GPR116 activation in the tethered agonist sequence and in extracellular loops 2/3 (ECL2/3). We further highlight residues in transmembrane 7 (TM7) that mediate stronger signaling in mouse versus human GPR116 and recapitulate these findings in a model supporting tethered agonist:ECL2 interactions for GPR116 activation.
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Surfactantes Pulmonares , Aminoácidos , Animales , Humanos , Ratones , Ratones Noqueados , Péptidos , Surfactantes Pulmonares/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transducción de SeñalRESUMEN
OBJECTIVE: While microscale pedestrian environment features such as sidewalks and crosswalks can affect pedestrian safety, it is challenging to assess microscale environment associated risk across locations or at scale. Addressing these challenges requires an efficient auditing protocol that can be used to assess frequencies of microscale environment features. For this reason, we developed an eight-item pedestrian environment virtual audit protocol and conducted a descriptive epidemiologic study of pedestrian injury in Washington State, USA. METHODS: We used data from police reports at pedestrian-automotive collision sites where the pedestrian was seriously injured or died. At each collision site, high school students participating in an online summer internship program virtually audited Google Street View imagery to assess the presence of microscale pedestrian environment features such as crosswalks and streetlighting. We assessed inter-rater reliability using Cohen's kappa and explored prevalence of eight microscale environment features in relation to injury severity and municipal boundaries. RESULTS: There were 2248 motor vehicle crashes eliciting police response and resulting in death or serious injury of a pedestrian in Washington State between January 1, 2015 and May 8, 2020. Of the crashes resulting in serious injury or death, 498 (22%) resulted in fatalities and 1840 (82%) occurred within municipal boundaries. Cohen's kappa scores for the eight pedestrian features that were audited ranged from 0.52 to 0.86. Audit results confirmed that features such as sidewalks and crosswalks were more common at collision sites within city limits. CONCLUSIONS: High school student volunteers with minimal training can reliably audit microscale pedestrian environments using limited resources.
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Peatones , Accidentes de Tránsito , Ciudades , Planificación Ambiental , Humanos , Reproducibilidad de los Resultados , Caminata , Washingtón/epidemiologíaRESUMEN
A series of deoxycholic acid-chalcone amides were synthesised and tested against the human lung cancer cell line, A549 and the cervical cancer cell line, SiHa. Among the synthesised deoxycholic acid-chalcone conjugates, some conjugates showed encouraging results as anticancer agents with good in vitro activity. More precisely, deoxycholic acid-chalcone conjugates 4b (IC50: 0.51 µM) and 4e (IC50: 0.84 µM) having 2nitrophenyl and 3,4,5trimethoxyphenyl groups exhibited a good activity against human cancer cell-line SiHa and while 4d (IC50: 0.25 µM) and 4b (IC50: 1.71 µM) showed better activity against A549 lung cancer cell line with respect to deoxycholic acid and chalcones. The anticancer activity of the bile acid conjugated chalcones was more than the activity of chalcone and deoxycholic acid alone. The results indicate that a bile acid conjugate strategy may be beneficial in improving the biological activity of chalcone derivatives. The enhanced activity of certain compounds may be due to their increased bioavailability.