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Background: Sickle cell disease (SCD) is a Mendelian disorder characterized by a point mutation in the β-globin gene that leads to sickling of erythrocytes. Several studies have shown that absolute neutrophil count is strongly associated with clinical severity of SCD, suggesting an apparent role of white blood cells (WBC) in SCD pathology. However, the mechanism by which genetic variants lead to WBC count differences in SCD patients remains unclear., Methods: Genome-wide association (GWA) analyses were carried out amongst a cohort of 2409 Brazil SCD participants. Association of WBC count and genetic markers were investigated in homozygous sickle cell anaemia participants and compound heterozygous sickle cell haemoglobin C participants., Results: GWA analysis showed that variants in genes TERT, ACKR1, and FAM3C are associated with WBC count variation. The well-studied association between WBC count and Duffy null phenotype (variant in ACKR1) in healthy populations was replicated, reinforcing the influence of the SNP rs2814778 (T>C) in WBC count., Conclusion: Genetics plays an important role in regulating WBC count in patients with SCD. Our results point to possible mechanisms involved in WBC count variation and as increased WBC count is associated with more severe SCD, these results could suggest potential therapeutic targets for individuals with SCD., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Cytopathology induced by methamphetamine (METH) is reminiscent of degenerative disorders such as Parkinson's disease, and it is characterized by membrane organelles arranged in tubulo-vesicular structures. These areas, appearing as clusters of vesicles, have never been defined concerning the presence of specific organelles. Therefore, the present study aimed to identify the relative and absolute area of specific membrane-bound organelles following a moderate dose (100 µM) of METH administered to catecholamine-containing PC12 cells. Organelles and antigens were detected by immunofluorescence, and they were further quantified by plain electron microscopy and in situ stoichiometry. This analysis indicated an increase in autophagosomes and damaged mitochondria along with a decrease in lysosomes and healthy mitochondria. Following METH, a severe dissipation of hallmark proteins from their own vesicles was measured. In fact, the amounts of LC3 and p62 were reduced within autophagy vacuoles compared with the whole cytosol. Similarly, LAMP1 and Cathepsin-D within lysosomes were reduced. These findings suggest a loss of compartmentalization and confirm a decrease in the competence of cell clearing organelles during catecholamine degeneration. Such cell entropy is consistent with a loss of energy stores, which routinely govern appropriate subcellular compartmentalization.

Background: The relationships between 25-hydroxyvitamin D [25(OH)D] and calcium and age-related macular degeneration (AMD) are unclear., Objectives: This study aimed to investigate the causal role of 25(OH)D concentrations, calcium concentrations, and dietary supplements use of vitamin D and calcium on risk of AMD and its subtypes., Methods: Independent genetic variants associated with 25(OH)D and calcium concentrations were used as instrumental variables in published genome-wide association studies (GWASs) of European ancestry. The bidirectional 2-sample Mendelian randomization (MR) analyses were performed using summary-level data from the UK Biobank and FinnGen datasets. Sensitivity analyses were conducted to ensure the robustness of the MR results. The meta-analyses were conducted using both fixed-effect and random-effect models to provide comprehensive and reliable estimates., Results: A standard deviation increase in calcium concentrations was linked to a 14%, 17%, and 13% reduction in the likelihood of developing AMD (95% confidence interval [CI]: 0.77, 0.97), wet AMD (95% CI: 0.73, 0.95), and dry AMD (95% CI: 0.75, 1.00), respectively. No significant causal relationships were detected between genetically predicted 25(OH)D concentrations and AMD and its subtypes (all P > 0.05). The combined analyses showed that higher calcium concentrations were associated with a reduced risk of overall AMD, with an odds ratio of 0.89 (95% CI: 0.81, 0.98)., Conclusions: This study provides evidence supporting the causal relationship between calcium concentrations and risk of AMD and its subtypes, which may have important implications for the prevention, monitoring, and treatment of AMD., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

The mortality rate among adolescents has been steadily increasing in recent years. Researchers have previously identified forms of externalizing psychopathology measured during adolescence associated with an increased risk for premature mortality, including attention-deficit/hyperactivity disorder (ADHD), substance use disorders (SUDs), oppositional defiant disorder (ODD), and conduct disorder (CD). The current study investigated whether additional personality traits (i.e., adolescent psychopathic traits, assessed via the Hare Psychopathy Checklist: Youth Version [PCL:YV]) were also associated with premature mortality risk among maximum-security incarcerated adolescents (N = 332). During a follow-up period ranging from 10 to 14 years, premature mortality was observed in n = 33 participants (9.94%), a mortality rate nearly ten times higher than population norms. We observed that adolescents scoring the highest on PCL:YV total scores exhibited significantly higher rates of premature mortality compared to adolescents scoring lower on PCL:YV total scores via Fisher's exact tests. Additionally, through univariate Cox proportional hazard regression analyses, PCL:YV total, Factor 2 (measuring lifestyle/behavioral and antisocial/developmental psychopathic traits), Facet 1 (measuring interpersonal psychopathic traits), and Facet 3 (measuring lifestyle/behavioral psychopathic traits) scores were associated with faster time to premature mortality. In supplemental analyses performed, we observed that adolescents meeting criteria for externalizing psychopathology (i.e., ADHD, SUDs, ODD, and CD) did not exhibit higher rates of premature mortality compared to control participants. The current study therefore identifies additional maladaptive personality traits to consider in relation to premature mortality risk (i.e., psychopathic traits) among a high-risk sample of incarcerated adolescents., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Based on safety and efficacy data, vaccinations are the best defense to protect persons and communities from serious vaccine-preventable diseases. The Advisory Committee on Immunization Practices recommends routine vaccination of adolescents aged 11-12 years with three vaccines including tetanus, diphtheria, and acellular pertussis vaccine; quadrivalent meningococcal conjugate vaccine; and human papillomavirus vaccine. CDC analyzed data from the 2023 National Immunization Survey-Teen for 16,658 adolescents aged 13-17 years (born during January 2005-December 2010) to assess vaccination coverage in 2023, recent trends in coverage by birth year, and trends in coverage by eligibility for the Vaccines for Children (VFC) program and birth year. In 2023, coverage with all routine vaccines recommended for adolescents was similar to coverage in 2022. Vaccination coverage among VFC-eligible adolescents was generally stable during the COVID-19 pandemic, except for a decrease in the percentage of VFC-eligible adolescents who were up to date with HPV vaccination by age 13 years among those born in 2010 compared with those born in 2007. Whereas coverage differences were found between VFC-eligible and non-VFC-eligible adolescents before the COVID-19 pandemic, coverage was similar among the most recent birth years in the survey. Providers should make strong recommendations for all routine vaccines and review adolescent vaccination records to verify if adolescents are up to date with all recommended vaccines., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Introduction: Treatment with the synaptic plasticity protein reelin has rapid antidepressant-like effects in adult corticosterone (CORT)-induced depressed rats, whether administered repeatedly or acutely. However, these effects remain unexplored in the context of post-partum depression (PPD)., Methods: This study investigated the antidepressant-like effect of a single injection of reelin in a CORT-induced model of PPD. Long-Evans female dams received either daily subcutaneous CORT (40 mg/kg) or saline injections (controls) from the post-partum day (PD) 2 to 22, and on PD22 were treated with a single intravenous reelin (3 μg) or vehicle injection., Results: Reelin treatment fully normalized to control levels the CORT-induced increase in Forced Swim Test (FST) immobility and the decrease in reelin-positive cells in the subgranular zone of the intermediate hippocampus. It also increased the number of oxytocin-positive cells in the paraventricular nucleus (PVN), the number of reelin-positive cells in the dorsal and ventral hippocampus, and the dendritic complexity of newborn neurons in the intermediate hippocampus, causing a partial recovery compared to controls. None of these changes were associated with fluctuations in estrogen levels measured peripherally., Discussion: This study brings new insights into the putative antidepressant-like effect of peripherally administered reelin in an animal model of PPD. Future studies should be conducted to investigate these effects on a dose-response paradigm and to further elucidate the mechanisms underlying the antidepressant-like effects of reelin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sánchez-Lafuente, Johnston, Reive, Scheil, Halvorson, Jimenez, Colpitts, Kalynchuk and Caruncho.)

Background: Consumption of pseudocereal-based foods decreased in phytate concentration can provide better nutrition concerning mineral bioavailability. This study aimed to evaluate the mineral bioavailability of quinoa sourdough-based snacks in a murine model. The mice were divided into five groups. One group was fed with basal snacks; three control groups received quinoa-based snacks made from non-fermented dough, dough without inoculum, and chemically acidified dough; and the test group (GF) received quinoa snacks elaborated from sourdough fermented by a phytase-positive strain, Lactiplantibacillus plantarum CRL 1964. Food intake, body weight, and mineral concentration in blood and organs (liver, kidney, and femur) were determined., Results: Food consumption increased during the feeding period and had the highest (16.2-24.5%) consumption in the GF group. Body weight also increased during the 6-weeks of trial. The GF group showed higher (6.0-10.2%) body weight compared with the other groups from the fifth week. The concentrations of iron, zinc, calcium, magnesium, and phosphorus in blood, iron and phosphorus in the liver, manganese and magnesium in the kidney, and calcium and phosphorus in the femur increased significantly (1.1-2.7-fold) in the GF group compared to the control groups., Conclusion: The diet that includes quinoa snacks elaborated with sourdough fermented by phytase-positive strain L. plantarum CRL 1964 increased the concentrations of minerals in the blood, liver, kidney, and femur of mice, counteracting the antinutritional effects of phytate. This study demonstrates that the diminution in phytate content and the consequent biofortification in minerals are a suitable tool for producing novel foods. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Combined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy significantly improves outcome for patients with estrogen receptor-positive (ER+) metastatic breast cancer, but drug resistance and thus disease progression inevitably occur. Herein, we aimed to identify genomic alterations associated with combined CDK4/6i and endocrine therapy resistance, and follow the levels of specific mutations in longitudinal circulating tumor DNA (ctDNA) for early detection of progression. From a cohort of 86 patients with ER+ metastatic breast cancer we performed whole exome sequencing or targeted sequencing of paired tumor (N = 8) or blood samples (N = 5) obtained before initiation of combined CDK4/6i and endocrine therapy and at disease progression. Mutations in oncogenic genes at progression were rare, while amplifications of growth-regulating genes were more frequent. The most frequently acquired alterations observed were PIK3CA and TP53 mutations and PDK1 amplification. Longitudinal ctDNA dynamics of mutant PIK3CA or private mutations revealed increased mutation levels at progression in 8 of 10 patients (80%). Impressively, rising levels of PIK3CA-mutated ctDNA were detected 4-17 months before imaging. Our data add to the growing evidence supporting longitudinal ctDNA analysis for real-time monitoring of CDK4/6i response and early detection of progression in advanced breast cancer. Further, our analysis suggests that amplification of growth-related genes may contribute to combined CDK4/6i and endocrine therapy resistance., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: We assessed human papillomavirus (HPV) vaccine effectiveness (VE) against anal HPV among men who have sex with men (MSM) in 2018-2023., Methods: Residual anal specimens from MSM without HIV ages 18-45 years were tested for HPV. We calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for associations between vaccination (≥1 dose) and quadrivalent vaccine (4vHPV)-type prevalence adjusting for city, race/ethnicity, and non-vaccine-type HPV prevalence, stratified by age group (18-26, 27-45). VE was calculated as (1-aPR)x100., Results: Among 2802 persons aged 18-26, 4vHPV-type prevalence was lower in those vaccinated at age <18 (aPR=0.13, CI: 0.08-0.22, VE=87%) and those vaccinated ≥2 years before specimen collection (aPR=0.52, CI: 0.42-0.64, VE=48%), compared with unvaccinated persons. Among 3548 persons aged 27-45, 4vHPV-type prevalence was lower in those vaccinated at ages 18-26 (aPR=0.68, CI: 0.57-0.82, VE=32%) and those vaccinated ≥2 years before specimen collection (aPR=0.66, CI: 0.57-0.77, VE=33%), compared with unvaccinated persons. While we observed no VE in persons vaccinated at age >26 overall, 4vHPV-type prevalence was lower in the subgroup vaccinated ≥2 years before specimen collection (aPR=0.71, CI: 0.56-0.89, VE=29%)., Conclusions: We found high VE against anal 4vHPV-type prevalence among MSM aged 18-26 who were vaccinated at age <18. Lower VE was observed among MSM ages 27-45 who were vaccinated at age 18-26 or ≥2 years before specimen collection. While ideally vaccination should be given at younger ages, vaccination can prevent some future infections in this population., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: Guidelines for the management of febrile infants emphasize patient-centered communication. Although patient-centeredness is central to high-quality health care, biases may impact physicians' patient-centeredness. We aimed to 1) identify physicians' assumptions that inform their communication with parents of febrile infants and 2) examine physicians' perceptions of bias., Methods: We recruited physicians from 3 academic pediatric emergency departments (EDs) for semistructured interviews. We applied a constant comparative method approach to conduct a thematic analysis of interview transcripts. Two coders followed several analytical steps: 1) discovery of concepts and code assignment, 2) identification of themes by grouping concepts, 3) axial coding to identify thematic properties, and 4) identifying exemplar excerpts for rich description. Thematic saturation was based on repetition, recurrence, and forcefulness., Results: Fourteen physicians participated. Participants described making assumptions regarding 3 areas: 1) the parent's affect, 2) the parent's social capacity, and 3) the physician's own role in the parent-physician interaction. Thematic properties highlighted the importance of the physician's assumptions in guiding communication and decision-making. Participants acknowledged an awareness of bias and specifically noted that language bias influenced the assumptions that informed their communication., Conclusions: ED physicians described subjective assumptions about parents that informed their approach to communication when caring for febrile infants. Given the emphasis on patient-centered communication in febrile infant guidelines, future efforts are necessary to understand how assumptions are influenced by biases, the effect of such behaviors on health inequities, and how to combat this., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Many studies have shown that morphological knowledge has effects on reading comprehension separate from other aspects of language knowledge. This has implications for reading instruction and assessment: it suggests that children could have reading comprehension difficulties that are due to a lack of morphological knowledge, and thus, that explicit instruction of morphology might be helpful for them, indeed for all children. To find children who might especially benefit from specific instruction in morphology, we would need good tests of morphological knowledge. We evaluated a set of morphological awareness assessments to determine whether they conclusively tapped into morphological knowledge, and found that it was not possible to be certain that they were accurately targeting morphological knowledge., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2024.)

Competing Interests: Disclosures The guest editors have no financial conflicts of interest and have nothing to disclose.

The threat of foreign animal diseases is steadily increasing. Veterinary practitioners play a vital role in a community's preparedness for, response to, and recovery from a foreign animal disease outbreak. This article examines the steps a practitioner needs to take to become ready to have a role in disaster readiness and response. Resources exist to provide the practitioner with tools needed to transition their normal daily activities to a larger integrated response. The knowledge and skills used by practitioners in disaster management lead to a more effective and efficient response to a foreign animal disease., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The current study mainly focused on provide further insights into the association of the miR-22-3p and miR-29c-3p expression in CFU-Hill colonies with birth weight and senescence process in children., Methods: This cross-sectional study evaluated 61 children (32 boys, 29 girls). The CFU-Hill colonies number was evaluated in vitro by cell culture technique and senescence was detected by β-galactosidase (SA-β-Gal) assay. Expression of miR-22-3p and miR-29c-3p isolated from CFU-Hill colonies were detected using quantitative real-time polymerase chain reaction., Results: Birth weight was correlated with both CFU-Hill colonies and %SA-β-Gal positive staining. Multivariate linear regression analysis revealed that the senescence was a predictor of the lower CFU-Hill colonies number, while only the birth weight was a predictor of senescence of CFU-Hill colonies. Overexpression of miR-22-3p and miR-29c-3p was observed in CFU-Hill colonies isolated from children with low birth weight (LBW). Interestingly, we found a significant correlation between %SA-β-Gal cells staining positive for both miR-22-3p and miR-29c-3p., Conclusion: The LBW is associated with decreased CFU-Hill colonies number and high senescence of these cells. The overexpression of miR-22-3p and miR-29c-3p may be partially responsible for this alteration due to regulation of several pathways related to the senescence process., Impact: The study establishes a significant correlation between birth weight and the number of CFU-Hill colonies, suggesting that birth weight could be a predictive biomarker for vascular health in children. Data indicates that cellular senescence is a predictor of reduced CFU-Hill colony numbers. This suggests that the aging process of these cells could be an important factor in understanding the vascular health issues in children with low birth weight. The overexpression of miR-22-3p and miR-29c-3p in children with low birth weight and their correlation with increased cellular senescence highlight these microRNAs as possible molecular mechanisms influencing the aging of CFU-Hill colonies., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Psychopathic traits have been associated with rearrest in adolescents involved in the criminal legal system. Much of the prior work has focused on White samples, short follow-up windows, and relatively low-risk youth. The current study aimed to evaluate the utility of the Hare Psychopathy Checklist: Youth Version (PCL:YV) for predicting general and violent felony recidivism in a large sample of high-risk, predominantly Hispanic/Latino, male adolescents (n = 254) with a five-year follow-up period. Results indicated higher PCL:YV scores and lower full-scale estimated IQ scores were significantly associated with a shorter time to felony and violent felony rearrest. These effects generalized to Hispanic/Latino adolescents (n = 193)-a group that faces disproportionate risk of being detained or committed to juvenile correctional facilities in the U.S. These results suggest that expert-rated measures of psychopathic traits and IQ are reliable predictors of subsequent felony and violent felony rearrest among high-risk male adolescents., (© 2024. The Author(s).)

Introduction: Optimal pain control methods after total shoulder arthroplasty (TSA) achieve reduced opioid consumption, shortened hospital stay, and improved patient satisfaction in addition to adequate analgesia. Interscalene brachial plexus block is the gold standard for TSA, yet it typically does not provide pain relief lasting beyond 24 hours. Liposomal bupivacaine (LB) purportedly provides prolonged analgesia, yet it has been minimally explored for interscalene block, and it is significantly more expensive than standard bupivacaine., Methods: This is a prospective, 2-arm, double-blinded randomized controlled trial. Subjects presenting for anatomic or reverse TSA were randomized in a 1:1 ratio to receive interscalene brachial plexus block with either LB plus bupivacaine (LBB group) or bupivacaine plus dexamethasone and epinephrine (BDE group). The primary outcome was 120-hour postoperative opioid consumption. Secondary outcomes were pain scores up to 96 hours postoperatively, pain control satisfaction, complications, level of distress from block numbness, and hospital stay., Results: Ninety patients, 45 per group, were included in the intention-to-treat analysis and randomized. Because of withdrawal of consent and loss to follow-up, 40 in each group completed enrollment through postoperative day 60. Total 120-hour postoperative opioid consumption was similar between groups (P = .127), with no differences within 24- or 48-hour time intervals. Postoperative pain scores at 24-48 hours, 48-72 hours, 72-96 hours, and day 60 were significantly lower for the LBB group., Discussion: LB interscalene brachial plexus block before total shoulder arthroplasty did not reduce 120-hour postoperative opioid consumption but significantly reduced postoperative pain between 24 and 96 hours and at postoperative day 60., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Neonatal chest-Xray (CXR)s are commonly performed as a first line investigation for the evaluation of respiratory complications. Although lung area derived from CXRs correlates well with functional assessments of the neonatal lung, it is not currently utilised in clinical practice, partly due to the lack of reference ranges for CXR-derived lung area in healthy neonates. Advanced MR techniques now enable direct evaluation of both fetal pulmonary volume and area. This study therefore aims to generate reference ranges for pulmonary volume and area in uncomplicated pregnancies, evaluate the correlation between prenatal pulmonary volume and area, as well as to assess the agreement between antenatal MRI-derived and neonatal CXR-derived pulmonary area in a cohort of fetuses that delivered shortly after the antenatal MRI investigation., Methods: Fetal MRI datasets were retrospectively analysed from uncomplicated term pregnancies and a preterm cohort that delivered within 72 h of the fetal MRI. All examinations included T2 weighted single-shot turbo spin echo images in multiple planes. In-house pipelines were applied to correct for fetal motion using deformable slice-to-volume reconstruction. An MRI-derived lung area was manually segmented from the average intensity projection (AIP) images generated. Postnatal lung area in the preterm cohort was measured from neonatal CXRs within 24 h of delivery. Pearson correlation coefficient was used to correlate MRI-derived lung volume and area. A two-way absolute agreement was performed between the MRI-derived AIP lung area and CXR-derived lung area., Results: Datasets from 180 controls and 10 preterm fetuses were suitable for analysis. Mean gestational age at MRI was 28.6 ± 4.2 weeks for controls and 28.7 ± 2.7 weeks for preterm neonates. MRI-derived lung area correlated strongly with lung volumes (p < 0.001). MRI-derived lung area had good agreement with the neonatal CXR-derived lung area in the preterm cohort [both lungs = 0.982]., Conclusion: MRI-derived pulmonary area correlates well with absolute pulmonary volume and there is good correlation between MRI-derived pulmonary area and postnatal CXR-derived lung area when delivery occurs within a few days of the MRI examination. This may indicate that fetal MRI derived lung area may prove to be useful reference ranges for pulmonary areas derived from CXRs obtained in the perinatal period., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Cancer continues to be a serious threat to human health worldwide. Lung, prostate and triple-negative breast cancers are amongst the most incident and deadliest cancers. Steroidal compounds are one of the most diversified therapeutic classes of compounds and they were proven to be efficient against several types of cancer. The epoxide function has been frequently associated with anticancer activity, particularly the 1,2-epoxide function. For this reason, three 1,2-epoxysteroid derivatives previously synthesised (EP1, EP2 and EP3) and one synthesised for the first time (oxysteride) were evaluated against H1299 (lung), PC3 (prostate) and HCC1806 (triple-negative breast) cancer cell lines. A human non-tumour cell line, MRC-5 (normal lung cell line) was also used. EP2 was the most active compound in all cell lines with IC 50 values of 2.50, 3.67 and 1.95 µM, followed by EP3 with IC 50 values of 12.65, 15.10 and 14.16 µM in H1299, PC3 and HCC1806 cells, respectively. Additional studies demonstrated that EP2 and EP3 induced cell death by apoptosis at lower doses and apoptosis/necrosis at higher doses, proving that their effects were dose-dependent. Both compounds also exerted their cytotoxicity by ROS production and by inducing double-strand breaks. Furthermore, EP2 and EP3 proved to be much less toxic against a normal lung cell line, MRC5, indicating that both compounds might be selective, and they also demonstrated suitable in silico ADME and toxicity parameters. Finally, none of the compounds induced haemoglobin release. Altogether, these results point out the extreme relevance of both compounds, especially EP2, in the potential treatment of these types of cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cinnamic acids are aromatic acids primarily found in plants and plant-derived food. Phenolic cinnamic acids, with one or more hydroxyl groups in the aromatic ring, often contribute to the biological activities attributed to these compounds. The presence of hydroxyl groups and a carboxyl group makes cinnamic acids very hydrophilic, preventing them from crossing biological membranes and exerting their biological activities. To alleviate this condition, a panel of synthetic modifications have been made leading to a diverse set of phenolic cinnamic structures. In this review, an overview of the natural phenolic cinnamic acid derivatives and their plant sources (more than 200) is described. The synthetic approaches to obtain the referred derivatives (more than 200) namely esters and amides are reviewed. Further, their anti-inflammatory activity (more than 70 compounds) is scrutinized. Finally, future directions will be indicated to translate the research on phenolic cinnamic derivatives into potentially effective anti-inflammatory drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Some public health professionals have expressed concern that the COVID-19 pandemic has increased vaccine hesitancy about routine childhood vaccines; however, the differential prevalence of vaccine hesitancy about specific vaccines has not been measured., Methods: Data from the National Immunization Survey-Child COVID-19 Module (NIS-CCM) were analyzed to assess the proportion of children ages 6 months-17 years who have a parent with hesitancy about: COVID-19, influenza, human papillomavirus (HPV) (for children ≥ 9 years) vaccines, and "all other childhood shots." Interviews from October 2022 through April 2023 were analyzed., Results: The percentage of children with a vaccine-hesitant parent varied by vaccine. 55.9% of children had a parent hesitant about COVID-19 vaccine, 30.9% hesitant about influenza vaccine, 30.1% hesitant about HPV vaccine, and 12.2% had a parent hesitant about other vaccines such as measles, polio, and tetanus., Conclusion: The study findings suggest that differential interventions and communications to parents be used to educate about COVID-19, influenza, HPV, and routine childhood vaccinations because the hesitancy levels differ widely., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Objective: A cancer diagnosis during adolescence and young adulthood (AYA) disrupts AYAs' identity formation, a critical task for healthy development, and contributes to psychological distress called identity distress. Clinical communication is central to promoting AYAs' healthy identity development. We sought to identify aspects of clinician-diagnosed AYA communication that can promote AYAs' identity development and potentially buffer them from distress., Methods: In-depth, semi-structured interviews were conducted with two groups (AYA oncology clinicians and diagnosed AYAs). Transcripts were thematically analyzed to capture communication that clinicians and AYAs perceive promotes AYAs' identity development and buffers related distress., Results: Fourteen diagnosed AYAs and 7 clinicians identified three clinician- or AYA-led communication approaches and associated strategies that they perceive can buffer identity distress and promote identity development: 1) clinicians' using person-centered communication (e.g., empathic communication); 2) promoting AYAs' control/self-management of care (e.g., not dictating AYAs' behavior); and 3) prioritizing/seeing the person behind the patient (e.g., knowing the AYA as a person)., Conclusion/practice Implications: Both AYA oncology clinicians and diagnosed AYAs can communicate in ways that protect AYAs' identity development and related psychological well-being. Findings can be implemented into targeted communication skills interventions to teach health-promoting behavior and augment AYAs' psychosocial oncology care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare.

Clinical implementation of evidence-based practice (EBP) tools is a healthcare priority. The Dynamic Grade of Swallowing Toxicity (DIGEST) is an EBP tool developed in 2016 for videofluoroscopy in head and neck (H&N) oncology with clinical implementation as a goal. We sought to examine: (1) feasibility of clinical implementation of DIGEST in a national comprehensive cancer center, and (2) fidelity of DIGEST adoption in real-world practice. A retrospective implementation evaluation was conducted in accordance with the STARI framework. Electronic health record (EHR) databases were queried for all consecutive modified barium swallow (MBS) studies conducted at MD Anderson Cancer Center from 2016 to 2021. Implementation outcomes included: feasibility as measured by DIGEST reporting in EHR (as a marker of clinical use) and fidelity as measured by accuracy of DIGEST reporting relative to the decision-tree logic (penetration-aspiration scale [PAS], residue, and Safety [S] and Efficiency [E] grades). Contextual factors examined included year, setting, cancer type, MBS indication, and provider. 13,055 MBS were conducted by 29 providers in 7,842 unique patients across the lifespan in diverse oncology populations (69% M; age 1-96 years; 58% H&N cancer; 10% inpatient, 90% outpatient). DIGEST was reported in 12,137/13,088 exams over the 6-year implementation period representing 93% (95% CI: 93-94%) adoption in all exams and 99% (95% CI: 98-99%) of exams excluding the total laryngectomy population (n = 730). DIGEST reporting varied modestly by year, cancer type, and setting/provider (> 91% in all subgroups, p < 0.001). Accuracy of DIGEST reporting was high for overall DIGEST (incorrect SE profile 1.6%, 200/12,137), DIGEST-safety (incorrect PAS 0.4% 51/12,137) and DIGEST-efficiency (incorrect residue 1.2%, 148/12,137). Clinical implementation of DIGEST was feasible with high fidelity in a busy oncology practice across a large number of providers. Adoption of the tool across the lifespan in diverse cancer diagnoses may motivate validation beyond H&N oncology., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Traumatic brain injury (TBI) is a global public health problem and is highly prevalent among justice-involved populations. Pediatric TBI is linked with long-term negative outcomes and is correlated with substance use, criminal behavior, psychiatric disorders, and disruptions in neurocognition. These same TBI correlates are evident among youth with psychopathic traits. Given ongoing neurobiological and social development in adolescence, understanding the link between psychopathic traits and TBI in justice-involved youth is critical. A sample of 263 male adolescents were recruited from a maximum-security juvenile justice facility. Using a structural equation modeling (SEM) framework, measurement invariance of psychopathic traits (TBI ±) was tested, and psychopathy scores were accounted for in terms of TBI variables (severity, age of first TBI, total number), participant's age, IQ, substance use, and internalizing psychopathology. There was evidence of strong invariance across TBI status and those with TBI had higher affective and impulsive lifestyle psychopathic traits than adolescents without TBI. The SEM indicated that TBI severity was associated with lower IQ scores, which in turn were associated with increased lifestyle/antisocial (Factor 2) psychopathic traits. Total number of TBIs was associated with higher substance use, which was associated with both increased interpersonal/affective (Factor 1) and Factor 2 psychopathic traits. These TBI variables also had indirect associations with psychopathic traits through IQ and substance use. The findings indicate that TBI is associated with psychopathic traits and suggest that disturbances in cognition and substance use may be treatment targets for youth with TBI and psychopathic traits., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Interventions are needed to increase low HPV vaccination rates within rural areas in the United States, particularly in the state of Florida, which has the seventh highest number of HPV-related cancers. Florida also ranks low compared to other states in terms of HPV vaccination. Rural-residing parents may benefit from two evidence-based strategies to increase vaccination rates: reminder messages informing and prompting vaccination appointments and mobile clinics to reduce transportation barriers. We sought to identify parental attitudes towards (1) message features that promote rural-residing parents' receptivity to HPV vaccination; (2) parents' acceptability of three reminder message modalities (text, postcard, phone); and (3) implementation factors that promote parents' acceptability of using a mobile clinic for vaccination. We recruited 28 rural-residing parents of 9- to 12-year-old children (unvaccinated for HPV) for focus group and individual interviews and thematically analyzed transcripts. Three features promoted parents' receptivity to HPV vaccination messages: source credibility , specific information coverage , and personalization (name and birthday wishes) . Parents most preferred text messages and identified three factors promoting parents' mobile clinic use: convenience and feasibility, trustworthiness, and detailed information . The findings indicate rural-residing parents' acceptability of reminder messages and mobile clinics as well as the importance of trust and feasibility when implementing these evidence-based strategies for rural-residing parents.

There is an urgent need for novel antidepressants, given that approximately 30% of those diagnosed with depression do not respond adequately to first-line treatment. Additionally, monoaminergic-based antidepressants have a substantial therapeutic time-lag, often taking months to reach full therapeutic effect. Ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist is the only current effective rapid-acting antidepressant, demonstrating efficacy within hours and lasting up to two weeks with an acute dose. Reelin, an extracellular matrix glycoprotein, has demonstrated rapid-acting antidepressant-like effects at 24 h, however the exact timescale of these effects has not been investigated. To determine the short and long-term effects of reelin, female Long Evans rats (n = 120) underwent a chronic corticosterone (CORT; or vehicle) paradigm (40 mg/kg, 21 days). On day 21, rats were treated with reelin (3μg; i.v.), ketamine (10 mg/kg; i.p.), both reelin and ketamine (same doses), or vehicle (saline). Behavioural and biological effects were then evaluated at 1 h, 6 h, 12 h, and 1 week after treatment. The 1-week cohort continued CORT injections to ensure the effect of chronic stress was not lost. Individually, both reelin and ketamine significantly rescued CORT-induced behaviour and hippocampal reelin expression at all timepoints. Ketamine rescued a decrease in dendritic maturity as induced by CORT. Synergistic effects of reelin and ketamine appeared at 1-week, suggesting a potential additive effect of the antidepressant-like actions. Taken together, this study provides further support for reelin-based therapeutics to develop rapid-acting antidepressant., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: A unique feature of workplace investigations is the familiarity that investigators and witnesses have with the factors involved in the adverse incident. Familiarity creates expectations that can shape investigators' and witnesses' assumptions and opinions. The current research examined the biasing effect of non-factual witness claims on investigators' judgments. These claims, which we call 'uncheckable,' included opinions about factors involved in the event and the future. We also examined how participants' a priori knowledge of an employee's history influenced their judgments., Method: This experiment used a 2 (background information: control or unsafe) × 2 (uncheckable content: neutral or unsafe) between-subjects design. Participants were provided with background information about a worker (control or unsafe history) and a witness statement about a workplace event that contained uncheckable claims (neutral or worker as unsafe). We tested how our manipulations biased participants' judgments of: (i) the cause of the event, (ii) the witness's confidence and credibility, and (iii) the diagnosticity of the witness's account. We also tested if biasing background information affected how factual participants found the witness's statement., Results: Biasing uncheckable information (i.e., opinions) affected participants' judgments of event cause (ηp2 = 0.033) and increased their ratings of witness confidence (ηp2 = 0.074). Biasing background information about a worker affected participants' judgments of the cause of the event (ηp2 = 0.088), the diagnostic value of the witness statement (ηp2 = 0.054), and the number of factual claims in the witness statement, resulting in more uncheckable claims being misclassified as potential facts (ηp2 = 0.18)., Conclusion: This experiment demonstrated the significant effect that non-factual witness statements and irrelevant background information can have on the interpretation of evidence and judgments about the cause of events., Practical Application: Understanding how contextual information can bias investigative judgment helps workplace investigators manage its influence in their judgment practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 National Safety Council and Elsevier Ltd. All rights reserved.)

The microbiological quality of meat is influenced by the conditions of hygiene prevailing during production and handling. Thus, this study aimed to assess the prevalence of Salmonella enterica and its antimicrobial resistance, load of hygiene indicator bacteria including E. coli (ECC), coliforms (CC), total coliform (TCC), Enterobacteriaceae (EB) and aerobic plate count (APC), and meat handler's food safety knowledge and hygiene practices in butcher shops in two cities, Addis Ababa and Hawassa in Ethiopia, during 2020 and 2021. A total of 360 samples of beef carcasses (n = 120), knives (n = 60), chopping boards (n = 60), weighing balance (n = 60), and personnel's hands (n = 60) were randomly collected for microbial analysis. Besides, 120 participants were selected to participate in a food safety knowledge and hygiene practices assessment. The S. enterica isolates were identified by agglutination test followed by qPCR targeting invA gene. Phenotypic antimicrobial resistance profiles of S. enterica were determined using disk diffusion assays as described in CLSI. The ECC, CC, TCC, EB, and APC populations were quantified by plating onto petrifilm plates. A structured questionnaire was used to determine food safety knowledge and hygiene practices of participants. Overall prevalence of S. enterica was 16.7% (95% CI, 8.3-26.7) and location seems to have no effect (p = 0.806). Only 20% of the S. enterica were resistant to ampicillin and tetracycline. However, the majority (80%) of S. enterica isolates were susceptible to the panel of 11 antimicrobials tested. The overall mean ± SD (log CFU/cm 2 ) of ECC, CC, TCC, EB, and APC were 4.31 ± 1.15; 4.61 ± 1.33; 4.77 ± 1.32; 4.59 ± 1.38 and 5.87 ± 1.52, respectively. No significant difference (p = 0.123) in E. coli contamination was observed between samples of beef carcasses and chopping boards. The EB contamination showed no significant difference (p > 0.05) among sample sources. The APC contamination levels on beef carcass were significantly higher (p > 0.05) than other sample sources. A total of 56% (95% CI: 46.7 - 65.0) of the participants had poor knowledge and 65% (95% CI: 56.7 - 73.3) had poor hygiene practices towards food safety. This study highlighted the poor hygiene status of butcher facilities with a potential risk of beef safety. Thus, appropriate food safety control strategies and inspection is needed at retail establishments., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Background: Turning Point Analysis (TPA) is a methodological approach that allows scholars to retrospectively capture change over time by identifying instances of critical change (i.e., turning points) encountered across a given time period. While TPA has been used to examine time as a variable in health and illness experiences, the use of the method in behavioral medicine scholarship may be limited by the lack of understanding of TPA procedures and applicability., Objective: To describe how TPA has been used and enhance its accessibility by identifying and synthesizing methods of TPA data collection and analysis., Methods: A systematic search of electronic databases, including Academic Source Premier, Psychology and Behavioral Sciences Collection, APA PsycInfo, and ProQuest Dissertation and Theses Database, was conducted in May 2020. In July 2020, we used hand searching to identify additional articles, including forward and back tracking seminal articles on TPA. Studies were screened in duplicate., Results: Of the 1184 studies screened for this review, we included 52. Studies used TPA to examine relational (k = 40), organizational (k = 6), and individual (k = 6) variables and included an analysis of either turning points (k = 28), the trajectories of change over time created by the turning points (k = 3), or both (k = 21). Turning points and trajectories were captured and analyzed using qualitative and quantitative analytic approaches, with most studies using either purely qualitative (k = 26) or mixed methods (k = 21)., Conclusions: The findings of this review provide insight into the varied applications of TPA and suggest the potential value of this methodological approach in better understanding health experiences across time. By synthesizing the procedural and analytic steps to conducting a TPA, this review could also increase the accessibility and use of TPA in behavioral medicine research., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Cancer has become a chronic disease that requires a considerable amount of informal caregiving, often quite burdensome to family caregivers. However, the influence of spirituality on the caregivers' burden and mental health outcomes has been understudied. This study was to examine how caregiver burden, spirituality, and depression change during cancer treatment and investigate the moderating role of spirituality in the relationship between caregiver burden and depression for a sample of caregivers of persons with cancer., Methods: This secondary analysis used a longitudinal design employing 3 waves of data collection (at baseline, 3 months, and 6 months). Family caregivers completed the Caregiver Reaction Assessment, Spiritual Perspective Scale, and the PROMIS® depression measure. Linear mixed model analyses were used, controlling for pertinent covariates., Results: Spirituality, total caregiver burden, and depression remained stable over 6 months. More than 30% of the caregivers had mild to severe depressive symptoms at 3 time points. There was evidence of overall burden influencing depression. Of note was a protective effect of caregivers' spirituality on the relationship between depression and caregiver burden over time ( b = -1.35, p = .015). The lower the spirituality, the stronger the relationship between depression and burden, especially regarding subscales of schedule burden, financial burden, and lack of family support., Significance of Results: Spirituality was a significant resource for coping with caregiving challenges. This study suggests that comprehensive screening and spiritual care for cancer caregivers may improve their cancer caregiving experience and possibly influence the care recipients' health.

This work introduces the encapsulation of hexamethylene diisocyanate derivatives (HDI, TriHDI, and PHDI) with the biodegradable polymer poly(butylene adipate- co -terephthalate) (PBAT) through a solvent evaporation method. These microcapsules (MCs) were then employed in adhesive formulations for footwear. Moreover, MCs containing PHDI were produced in a closed vessel, demonstrating the potential for recovering and reusing organic solvents for the first time. The MCs were achieved with an isocyanate payload reaching up to 68 wt %, displaying a spherical shape, a core-shell structure, and thin walls without holes or cracks. The application of MCs as cross-linking agents for adhesives was evaluated following industry standards. The adhesives' strength surpassed the minimum requirement by a significant margin. Creep tests demonstrated that the formulation with MCs exhibits superior thermostability. Furthermore, the formulation with MCs-PHDI presented the best results reported to date for this type of system, as no displacement was observed in the bonded substrates. Environmental assessment indicates that adhesives with MCs have higher global warming potential (+16.2%) and energy consumption (+10.8%) than the standard commercial adhesives, but under alternative realistic scenarios, the differences can be insignificant. Therefore, adhesive formulations incorporating MCs promise to be on par with traditional adhesive systems regarding environmental impacts while providing benefits such as improved and safe handling of isocyanates and excellent bonding effectiveness., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Self-tracking and personal informatics offer important potential in chronic condition management, but such potential is often undermined by difficulty in aligning self-tracking tools to an individual's goals. Informed by prior proposals of goal-directed tracking, we designed and developed MigraineTracker, a prototype app that emphasizes explicit expression of goals for migraine-related self-tracking. We then examined migraine patient experiences in a deployment study for an average of 12+ months, including a total of 50 interview sessions with 10 patients working with 3 different clinicians. Patients were able to express multiple types of goals, evolve their goals over time, align tracking to their goals, personalize their tracking, reflect in the context of their goals, and gain insights that enabled understanding, communication, and action. We discuss how these results highlight the importance of accounting for distinct and concurrent goals in personal informatics together with implications for the design of future goal-directed personal informatics tools.

Objective: To assess recovery in childhood and adolescent vaccine ordering since initial declines in 2020 due to COVID-19 pandemic-related disruptions., Methods: Using vaccine ordering data provided by Merck & Co., Inc., Rahway, NJ, USA, the number of measles-containing vaccine doses ordered each month in the U.S. during January 1, 2020-May 31, 2022 were compared to doses ordered during the corresponding month in 2018 and human papillomavirus (HPV) vaccine doses ordered during January 1, 2020-December 31, 2022 were compared to corresponding month in 2019. Differences stratified by public vs. private funding source and state and urbanicity of the county where the provider is located were examined., Results: The cumulative deficit for measles-containing vaccines was 1,314,179 doses (-5.7%) as of May 2022 and 3,911,020 doses (-13.6%) for HPV vaccine as of December 2022. Deficits in publicly funded doses and HPV doses ordered in rural counties were greater than deficits in privately funded doses and HPV doses ordered in urban counties., Conclusions: Findings show that monthly measles-containing and HPV vaccine ordering has recovered; however, deficits remain. Greater deficits in publicly funded vaccine doses and HPV ordering in rural counties suggest varying level of recovery. To reduce gaps in deficits, health care providers are strongly encouraged to use every visit to recommend needed vaccines., Competing Interests: Declaration of competing interest The analysis reported in this paper was conducted by Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention without external funding. There was no financial support by Merck to conduct this analysis. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Adenosine A 2A receptor (A 2A R) antagonists are the leading nondopaminergic therapy to manage Parkinson's disease (PD) since they afford both motor benefits and neuroprotection. PD begins with a synaptic dysfunction and damage in the striatum evolving to an overt neuronal damage of dopaminergic neurons in the substantia nigra. We tested if A 2A R antagonists are equally effective in controlling these two degenerative processes. We used a slow intracerebroventricular infusion of the toxin MPP + in male rats for 15 days, which caused an initial loss of synaptic markers in the striatum within 10 days, followed by a neuronal loss in the substantia nigra within 30 days. Interestingly, the initial loss of striatal nerve terminals involved a loss of both dopaminergic and glutamatergic synaptic markers, while GABAergic markers were preserved. The daily administration of the A 2A R antagonist SCH58261 (0.1 mg/kg, i.p.) in the first 10 days after MPP + infusion markedly attenuated both the initial loss of striatal synaptic markers and the subsequent loss of nigra dopaminergic neurons. Strikingly, the administration of SCH58261 (0.1 mg/kg, i.p. for 10 days) starting 20 days after MPP + infusion was less efficacious to attenuate the loss of nigra dopaminergic neurons. This prominent A 2A R-mediated control of synaptotoxicity was directly confirmed by showing that the MPTP-induced dysfunction (MTT assay) and damage (lactate dehydrogenase release assay) of striatal synaptosomes were prevented by 50 nM SCH58261. This suggests that A 2A R antagonists may be more effective to counteract the onset rather than the evolution of PD pathology.

Background and Hypothesis: The decision for acceptance or discard of the increasingly rare and marginal brain-dead donor kidneys in Eurotransplant (ET) countries has to be made without solid evidence. Thus, we developed and validated flexible clinicopathological scores called 2-Step Scores for the prognosis of delayed graft function (DGF) and one-year death-censored transplant loss (1y-tl) reflecting the current practice of six ET countries including Croatia and Belgium., Methods: The training set was n=620 for DGF and n=711 for 1y-tl, with validation sets n=158 and n=162. In step 1, stepwise logistic regression models including only clinical predictors were used to estimate the risks. In step 2, risk estimates were updated for statistically relevant intermediate risk percentiles with nephropathology., Results: Step 1 revealed an increased risk of DGF with increased cold ischaemia time, donor and recipient BMI, dialysis vintage, number of HLA-DR mismatches or recipient CMV IgG positivity. On the training and validation set, c-statistics were 0.672 and 0.704, respectively. At a range between 18% and 36%, accuracy of DGF-prognostication improved with nephropathology including number of glomeruli and Banff cv (updated overall c statistics of 0.696 and 0.701, respectively).Risk of 1y-tl increased in recipients with cold ischaemia time, sum of HLA-A. -B, -DR mismatches and donor age. On training and validation sets, c-statistics were 0.700 and 0.769, respectively. Accuracy of 1y-tl prediction improved (c-statistics = 0.706 and 0.765) with Banff ct. Overall, calibration was good on the training, but moderate on the validation set; discrimination was at least as good as established scores when applied to the validation set., Conclusion: Our flexible 2-Step Scores with optional inclusion of time-consuming and often unavailable nephropathology should yield good results for clinical practice in ET, and may be superior to established scores. Our scores are adaptable to donation after cardiac death and perfusion pump use., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

In the search for novel, effective inhibitors of High-Mobility Group Box1 (HMGB1)-a protein involved in various inflammatory and autoimmune diseases as well as in cancer-we herein discovered a set of anti-HMGB1 G-quadruplex(G4)-forming aptamers by using an in vitro selection procedure applied to a doped library of guanine-rich oligonucleotides. The selected DNA sequences were then studied in a pseudo-physiological buffer mimicking the extracellular medium, where HMGB1 exerts its pathological activity, using spectroscopic, electrophoretic, and chromatographic techniques. All the oligonucleotides proved to fold into monomeric G4s and in some cases also dimeric species, stable at physiological temperature. Remarkably, the protein preferentially recognized the sequences forming dimeric parallel G4 structures, as evidenced by a properly designed chemiluminescent binding assay which also highlighted a good selectivity of these aptamers for HMGB1. Moreover, all aptamers showed anti-HMGB1 activity, inhibiting protein-induced cell migration. The acquired data allowed identifying L12 as the best anti-HMGB1 aptamer, featured by high thermal and enzymatic stability, no toxicity at least up to 5 μM concentration on healthy cells, along with potent anti-HMGB1 activity (IC 50 ca. 28 nM) and good binding affinity for the protein, thus indicating it as a very promising lead candidate for in vivo studies., (© 2024 Wiley‐VCH GmbH.)

Purpose: The overall goal of this review was to identify what is known about triadic (clinician-patient-caregiver) communication in mild cognitive impairment (MCI) and dementia care settings throughout the care continuum., Methods: Using a structured search, we conducted a systematic scoping review of relevant published journal articles across 5 databases. Study titles/abstracts and selected full-text articles were screened by 2 investigators in Covidence systematic review software. Articles were excluded if they were not about clinical communication, focused only on caregiver-patient communication or communication in residential care, were interventional, lacked empirical data, or were not in English. Extracted data were documented using Google Forms., Results: The study team screened 3426 article titles and abstracts and 112 full-text articles. Forty-four articles were included in the final review. Results were categorized by 3 communication scenarios: diagnostic communication (n=22), general communication (n=16), and advanced care planning communication (n=6)., Conclusions and Relevance: Across the included articles, the conceptualization and assessment of communication lacked homogeneity. Future directions include addressing these research gaps, establishing recommendations for clinicians to effectively communicate with individuals with dementia and caregivers, and creating and testing communication skills trainings for caregivers/family members, clinicians, and/or individuals with dementia to facilitate effective communication., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Family caregivers (FCs) of a patient with chronic lymphocytic leukemia (CLL) can encounter unpredictable challenges and care demands. They can experience high levels of burden, a loss of self-care, and poor quality of life. Their receipt of social support and ability to communicate with clinicians may impact their burden. FCs would benefit from educational resources that teach them communication skills central to their ability to obtain the support they need-support that is imperative to reducing burden. To better target psychosocial educational interventions focused on social support and communication skills, we aimed to explore the relationship between social support, sources of support, and burden; the relationship between FCs' clinical communication and their perceptions of support and burden; and any unmet support needs. A total of 575 CLL FCs completed an online survey of validated scales about social support, burden, and clinical communication, as well as an open-ended item in which they reported any unmet support needs. Statistical analyses showed that FCs who perceived they were more supported reported less burden, and female FCs reported more burden than males. Support from family, friends, and professionals collectively contributed to FCs' support. FCs who perceived they had stronger communication skills with their loved one's clinicians reported more social support. FCs identified six areas of unmet support needs: financial, emotional, informational, instrumental, peer, and communication support. Collectively, findings show that increased social support can reduce FCs' burden and qualitative findings provide a roadmap of social support domains to target that could potentially improve the caregiving experience., (© 2023. The Author(s) under exclusive licence to American Association for Cancer Education.)

Methamphetamine (METH) produces a cytopathology, which is rather specific within catecholamine neurons both in vitro and ex vivo, in animal models and chronic METH abusers. This led some authors to postulate a sort of parallelism between METH cytopathology and cell damage in Parkinson's disease (PD). In fact, METH increases and aggregates alpha-syn proto-fibrils along with producing spreading of alpha-syn. Although alpha-syn is considered to be the major component of aggregates and inclusions developing within diseased catecholamine neurons including classic Lewy body (LB), at present, no study provided a quantitative assessment of this protein in situ, neither following METH nor in LB occurring in PD. Similarly, no study addressed the quantitative comparison between occurrence of alpha-syn and other key proteins and no investigation measured the protein compared with non-protein structure within catecholamine cytopathology. Therefore, the present study addresses these issues using an oversimplified model consisting of a catecholamine cell line where the novel approach of combined light and electron microscopy (CLEM) was used measuring the amount of alpha-syn, which is lower compared with p62 or poly-ubiquitin within pathological cell domains. The scenario provided by electron microscopy reveals unexpected findings, which are similar to those recently described in the pathology of PD featuring packing of autophagosome-like vesicles and key proteins shuttling autophagy substrates. Remarkably, small seed-like areas, densely packed with p62 molecules attached to poly-ubiquitin within wide vesicular domains occurred. The present data shed new light about quantitative morphometry of catecholamine cell damage in PD and within the addicted brain., (© 2024. The Author(s).)

Increasing survivorship in kidney cancer patients has shifted treatment strategies to optimize renal function preservation. In 2010, the College of American Pathologists (CAP) updated their synoptic reporting guidelines for tumor nephrectomies to require evaluation of the nonneoplastic kidney parenchyma. We conducted this study to understand current practice behaviors regarding the evaluation of the nonneoplastic kidney parenchyma in tumor nephrectomy specimens. We emailed a 14-item multiple-choice survey to members of the Renal Pathology Society and Genitourinary Pathology Society. We also emailed a 12-item survey to program and associate program directors of American pathology residencies to assess the current state of renal pathology education. Ninety-eight genitourinary and 104 renal pathologists responded to the survey on the nonneoplastic kidney parenchyma. Ninety-five percent of respondents who examine tumor nephrectomies reported evaluating the nonneoplastic kidney parenchyma. Seventy-five percent of genitourinary pathologists and 67% of renal pathologists use synoptic reporting, and 81% use the CAP protocol. Thirty-nine percent of respondents report always contacting the clinician when they find evidence of medical renal disease. Forty-two program leaders responded to our renal pathology education survey, and 64% of them have a mandatory renal pathology rotation that on average lasts about 2 to 4 weeks. The majority of pathologists examine the nonneoplastic kidney parenchyma of tumor nephrectomies and frequently report incidences of new medical renal disease directly to clinicians, but there remains room for improvement and educational gaps during residency training. Further efforts to standardize both this evaluation and renal pathology education will improve patient care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Common genetic variants confer substantial risk for chronic lung diseases, including pulmonary fibrosis. Defining the genetic control of gene expression in a cell-type-specific and context-dependent manner is critical for understanding the mechanisms through which genetic variation influences complex traits and disease pathobiology. To this end, we performed single-cell RNA sequencing of lung tissue from 66 individuals with pulmonary fibrosis and 48 unaffected donors. Using a pseudobulk approach, we mapped expression quantitative trait loci (eQTLs) across 38 cell types, observing both shared and cell-type-specific regulatory effects. Furthermore, we identified disease interaction eQTLs and demonstrated that this class of associations is more likely to be cell-type-specific and linked to cellular dysregulation in pulmonary fibrosis. Finally, we connected lung disease risk variants to their regulatory targets in disease-relevant cell types. These results indicate that cellular context determines the impact of genetic variation on gene expression and implicates context-specific eQTLs as key regulators of lung homeostasis and disease., (© 2024. The Author(s).)

The loose-equilibrium concept (LEC) predicts that ecological assemblages change transiently but return towards an earlier or average structure. The LEC framework can help determine whether assemblages vary within expected ranges or are permanently altered following environmental change. Long-lived, slow-growing animals typically respond slowly to environmental change, and their assemblage dynamics may respond over decades, which transcends most ecological studies. Unionid mussels are valuable for studying dynamics of long-lived animals because they can live >50 years and occur in dense, species-rich assemblages (mussel beds). Mussel beds can persist for decades, but disturbance can affect species differently, resulting in variable trajectories according to differences in species composition within and among rivers. We used long-term data sets (10-40 years) from seven rivers in the eastern United States to evaluate the magnitude, pace and directionality of mussel assemblage change within the context of the LEC. Site trajectories varied within and among streams and showed patterns consistent with either the LEC or directional change. In streams that conformed to the LEC, rank abundance of dominant species remained stable over time, but directional change in other streams was driven by changes in the rank abundance and composition of dominant species. Characteristics of mussel assemblage change varied widely, ranging from those conforming to the LEC to those showing strong directional change. Conservation approaches that attempt to maintain or create a desired assemblage condition should acknowledge this wide range of possible assemblage trajectories and that the environmental factors that influence those changes remain poorly understood., (© 2024 The Authors. Journal of Animal Ecology © 2024 British Ecological Society.)

The use of predators and predator odor as stressors is an important and ecologically relevant model for studying the impact of behavioral responses to threat. Here we summarize neural substrates and behavioral changes in rats resulting from predator exposure. We briefly define the impact predator exposure has on neural targets throughout development (neonatal, juvenile, and adulthood). These findings allow us to conceptualize the impact of predator exposure in the brain, which in turn may have broader implications for human disorders such as PTSD. Importantly, inclusion of sex as a biological variable yields distinct results that may indicate neural substrates impacted by predator exposure differ based on sex., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kigar, Cuarenta, Zuniga, Chang, Auger and Bakshi.)

Importance: Life expectancy is decreasing in the US. Without national efforts to address factors that support policies and programs directed at children living in areas of concentrated poverty, life expectancy will likely continue to decline while costs and suffering associated with unnatural deaths will increase., Objective: To identify which childhood factors are associated with death from unnatural causes through midadulthood., Design, Setting, and Participants: For this cohort study, longitudinal data on childhood characteristics came from a group-randomized intervention trial implemented in Baltimore City Public Schools, Baltimore, Maryland (baseline 1985-1986; all students entering first grade were selected to participate at age 6 years). Participants were followed up to midadulthood with a National Death Index search through December 31, 2020. Data analysis was performed from February to May 2023., Exposures: Exposures included individual factors (ie, sociodemographic characteristics, teacher-reported aggressive behavior, self-reported depression, anxiety, early alcohol and cannabis use, and assaultive violence exposure), family and peer factors (ie, household structure and education level, deviant peer affiliation, and parental monitoring), and neighborhood factors (ie, rates of neighborhood assault and public assistance)., Main Outcomes and Measures: The main outcome was unnatural death, defined as death due to unintentional injury, suicide, and homicide. A National Death Index search ascertained participants who died by age 41 to 42 years and cause of death. Multivariable Cox proportional hazards models were used to identify whether the exposures were independently associated with future mortality by unnatural causes., Results: The initial trial included 2311 children, and longitudinal data were available for 2180 participants (median [IQR] age in first grade, 6.3 [6.0-6.5] years; 1090 female [50.0%]; 1461 Black [67.0%]; 1168 received free or reduced lunch in first grade [53.6%]). A total of 111 male participants (10.2%) and 29 female participants (2.7%) died; among those who died, 96 male participants (86.5%) and 14 female participants (48.3%) died of unnatural causes. Two factors remained significantly associated with mortality from unnatural causes: female sex was associated with reduced risk (hazard ratio, 0.13; 95% CI, 0.08-0.22), and neighborhood public assistance was associated with increased risk (hazard ratio, 1.89; 95% CI, 1.09-3.30)., Conclusions and Relevance: In this urban population-based cohort study, no modifiable risk factors of mortality at the level of the individual (eg, depression or anxiety and substance use) or the family (eg, household education level) were identified. However, the degree of neighborhood poverty in early childhood was significantly associated with death by unnatural causes in early adulthood, suggesting that economic policies are needed to advance health equity in relation to premature mortality.

Purpose: Advances in radiation therapy have enabled the ability to deliver ablative treatments, but there has been limited application of these treatments to early-stage breast cancers with a goal of omitting surgery. The purpose of this study was to explore patient interest in pursuing nonsurgical treatment approaches for their early-stage breast cancer., Methods and Materials: We conducted a qualitative study involving interviews with 21 patients with early-stage breast cancer who were eligible for participation in a phase 2 clinical trial offering omission of definitive surgery. Interviews were transcribed and an inductive, thematic analysis was performed by 3 independent reviewers to generate themes and subthemes., Results: Data analysis revealed the following factors that affected patient willingness and desire to explore nonsurgical treatment options: (1) perceptions and feelings about their cancer; (2) current quality of life and the level of support available in their daily life; (3) external conversations focusing on family members' and friends' experiences with cancer and/or cancer treatments; (4) personal health care experiences, including their current breast cancer diagnosis; (5) perceptions and feelings about their physicians; (6) conversations with their physicians about their treatment options; and (7) self-identified desire to direct care decisions. Specifically, patients verbalized fearing surgery and surgical recovery; wanting to preserve their breast(s); the prior negative surgical experiences of friends, family, and themselves; a desire to receive treatment per the latest research; wanting to match the level of treatment with the severity of their cancer; and other comorbidities as reasons for wanting to explore omitting surgery., Conclusions: Our findings demonstrate an unmet need directed by patient interest to explore nonsurgical options for early-stage, biologically favorable breast cancer. These results may shape conversations around shared decision-making and clinical trial design, and result in more personalized treatment options for women with early-stage breast cancer., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To compare mean pulmonary T2* values and pulmonary volumes in fetuses that subsequently spontaneously delivered before 32 weeks with a control cohort with comparable gestational ages and to assess the value of mean pulmonary T2* as a predictor of preterm birth < 32 weeks' gestation., Methods: MRI datasets scanned at similar gestational ages were selected from fetuses who spontaneously delivered < 32 weeks of gestation and a control group who subsequently delivered at term with no complications. All women underwent a fetal MRI on a 3 T MRI imaging system. Sequences included T2-weighted single shot fast spin echo and T2* sequences, using gradient echo single shot echo planar sequencing of the fetal thorax. Motion correction was performed using slice-to-volume reconstruction and T2* maps generated using in-house pipelines. Lungs were manually segmented and volumes and mean T2* values calculated for both lungs combined and left and right lung separately. Linear regression was used to compare values between the preterm and control cohorts accounting for the effects of gestation. Receiver operating curves were generated for mean T2* values and pulmonary volume as predictors of preterm birth < 32 weeks' gestation., Results: Datasets from twenty-eight preterm and 74 control fetuses were suitable for analysis. MRI images were taken at similar fetal gestational ages (preterm cohort (mean ± SD) 24.9 ± 3.3 and control cohort (mean ± SD) 26.5 ± 3.0). Mean gestational age at delivery was 26.4 ± 3.3 for the preterm group and 39.9 ± 1.3 for the control group. Mean pulmonary T2* values remained constant with increasing gestational age while pulmonary volumes increased. Both T2* and pulmonary volumes were lower in the preterm group than in the control group for all parameters (both combined, left, and right lung (p < 0.001 in all cases). Adjusted for gestational age, pulmonary volumes and mean T2* values were good predictors of premature delivery in fetuses < 32 weeks (area under the curve of 0.828 and 0.754 respectively)., Conclusion: These findings indicate that mean pulmonary T2* values and volumes were lower in fetuses that subsequently delivered very preterm. This may suggest potentially altered oxygenation and indicate that pulmonary morbidity associated with prematurity has an antenatal antecedent. Future work should explore these results correlating antenatal findings with long term pulmonary outcomes., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Serving as a family caregiver for, and ultimately losing, a parent with advanced cancer in emerging and young adulthood has substantial, life phase-specific implications for psychosocial development. This qualitative study characterizes domains of psychosocial development impacted by cancer caregiving and parental death in this life phase. As part of a larger study, 33 bereaved emerging/young adult caregivers of parents who died following advanced cancer completed semi-structured interviews. A thematic analysis leveraging the constant comparative method was conducted by two coders and generated three themes, which described impacts of caregiving on: identity, life path, and relational intimacy and roles. Analyses also defined specific outcomes within these domains. Findings suggest that cancer caregiving-loss experiences can greatly influence developmental pursuits in this life phase. Findings validate a range of possible psychosocial impacts these caregivers may experience and can guide development of supportive resources for this growing subgroup of bereaved family caregivers.