Cryptic proteins translated from deletion-containing viral genomes dramatically expand the influenza virus proteome.

Productive infections by RNA viruses require faithful replication of the entire genome. Yet many RNA viruses also produce deletion-containing viral genomes (DelVGs), aberrant replication products with large internal deletions. DelVGs interfere with the replication of wild-type virus and their presence in patients is associated with better clinical outcomes. The DelVG RNA itself is hypothesized to confer this interfering activity. DelVGs antagonize replication by out-competing the full-length genome and triggering innate immune responses. Here, we identify an additionally inhibitory mechanism mediated by a new class of viral proteins encoded by DelVGs. We identified hundreds of cryptic viral proteins translated from DelVGs. These DelVG-encoded proteins (DPRs) include canonical viral proteins with large internal deletions, as well as proteins with novel C-termini translated from alternative reading frames. Many DPRs retain functional domains shared with their full-length counterparts, suggesting they may have activity during infection. Mechanistic studies of DPRs derived from the influenza virus protein PB2 showed that they poison replication of wild-type virus by acting as dominant-negative inhibitors of the viral polymerase. These findings reveal that DelVGs have a dual inhibitory mechanism, acting at both the RNA and protein level. They further show that DPRs have the potential to dramatically expand the functional proteomes of diverse RNA viruses.

Age of Juice Introduction and Cardiometabolic Outcomes in Middle Childhood.

BACKGROUND: The American Academy of Pediatrics recommends juice introduction after 12 months of age. Juice consumption has been linked to childhood obesity and cardiometabolic risk. OBJECTIVES: To examine the prospective relationship between the age of juice introduction and primary and secondary cardiometabolic outcomes in middle childhood. METHODS: Parents reported the age of juice introduction on Upstate KIDS questionnaires completed between 4 and 18 months. The quantity and type of juice introduced were not measured. Anthropometry, blood pressure (BP), and arterial stiffness by pulse wave velocity (PWV) were measured for 524 children (age, 8-10 y) at study visits (2017-2019). Age- and gender-adjusted z-scores were calculated using the Centers for Disease Control and Prevention reference for anthropometrics. Plasma lipids, hemoglobin A1c (HbA1c), and C-reactive protein (CRP) in a subset of children were also measured (n = 248). Associations between age at juice introduction (categorized as <6, 6 to <12, ≥12 months), and outcomes were estimated using mean differences and odds ratios, applying generalized estimating equations to account for correlations between twins. RESULTS: Approximately 18% of children were introduced to juice at <6 months, 52% between 6 and <12 months, and 30% ≥ 12 months of age. Children who were introduced to juice before 6 months had higher systolic BP (3.13 mmHg; 95% confidence interval [CI]: 0.52, 5.74), heart rate (4.46 bpm; 95% CI: 1.05, 7.87), and mean arterial pressure (2.08 mmHg; 95% CI: 0.15, 4.00) compared with those introduced ≥12 months after covariate adjustment including sociodemographic factors and maternal prepregnancy body mass index. No adjusted differences in anthropometry, lipids, HbA1c, and CRP levels were found. CONCLUSIONS: Early juice introduction during infancy was associated with higher systolic BP, heart rate, and mean arterial pressure in middle childhood. This trial was registered at clinicaltrials.gov as NCT03106493 (https://clinicaltrials.gov/study/NCT03106493?term=upstate%20KIDS&rank=1).

Activity-Based Protein Profiling to Probe Relationships between Cytochrome P450 Enzymes and Early-Age Metabolism of Two Polycyclic Aromatic Hydrocarbons (PAHs): Phenanthrene and Retene.

A growing body of literature has linked early-life exposures to polycyclic aromatic hydrocarbons (PAH) with adverse neurodevelopmental effects. Once in the body, metabolism serves as a powerful mediator of PAH toxicity by bioactivating and detoxifying PAH metabolites. Since enzyme expression and activity vary considerably throughout human development, we evaluated infant metabolism of PAHs as a potential contributing factor to PAH susceptibility. We measured and compared rates of phenanthrene and retene (two primary PAH constituents of woodsmoke) metabolism in human hepatic microsomes from individuals ≤21 months of age to a pooled sample (n = 200) consisting primarily of adults. We used activity-based protein profiling (ABPP) to characterize cytochrome P450 enzymes (CYPs) in the same hepatic microsome samples. Once incubated in microsomes, phenanthrene demonstrated rapid depletion. Best-fit models for phenanthrene metabolism demonstrated either 1 or 2 phases, depending on the sample, indicating that multiple enzymes could metabolize phenanthrene. We observed no statistically significant differences in phenanthrene metabolism as a function of age, although samples from the youngest individuals had the slowest phenanthrene metabolism rates. We observed slower rates of retene metabolism compared with phenanthrene also in multiple phases. Rates of retene metabolism increased in an age-dependent manner until adult (pooled) metabolism rates were achieved at ∼12 months. ABPP identified 28 unique CYPs among all samples, and we observed lower amounts of active CYPs in individuals ≤21 months of age compared to the pooled sample. Phenanthrene metabolism correlated to CYPs 1A1, 1A2, 2C8, 4A22, 3A4, and 3A43 and retene metabolism correlated to CYPs 1A1, 1A2, and 2C8 measured by ABPP and vendor-supplied substrate marker activities. These results will aid efforts to determine human health risk and susceptibility to PAHs exposure during early life.

Stereoselective Single Step Cyclization to Give Belt-Functionalized Pillar[6]arenes.

Two macrocycles were synthesized through cyclization reactions of secondary benzylic alcohols, giving pillar[6]arenes with a methyl substituent at each belt position. These macrocycles form stereoselectively with only the rtctct isomer with alternating up and down orientations of the belt methyl groups definitively identified. Isolated yields were modest (7 and 9%), but the macrocycles are prepared in a single step from either a commercially available alcohol or a very readily prepared precursor. X-ray crystal structures of the macrocycles indicate they have a capsule-like structure, which is far from the conventional pillar shape. Density functional theory calculations reveal that the energy barrier required to obtain the pillar conformation is significantly higher for these belt-functionalized macrocycles than for conventional belt-unfunctionalized pillar[6]arenes.

Predicting response to neoadjuvant chemotherapy for colorectal liver metastasis using deep learning on prechemotherapy cross-sectional imaging.

BACKGROUND AND OBJECTIVES: Deep learning models (DLMs) are applied across domains of health sciences to generate meaningful predictions. DLMs make use of neural networks to generate predictions from discrete data inputs. This study employs DLM on prechemotherapy cross-sectional imaging to predict patients' response to neoadjuvant chemotherapy. METHODS: Adult patients with colorectal liver metastasis who underwent surgery after neoadjuvant chemotherapy were included. A DLM was trained on computed tomography images using attention-based multiple-instance learning. A logistic regression model incorporating clinical parameters of the Fong clinical risk score was used for comparison. Both model performances were benchmarked against the Response Evaluation Criteria in Solid Tumors criteria. A receiver operating curve was created and resulting area under the curve (AUC) was determined. RESULTS: Ninety-five patients were included, with 33,619 images available for study inclusion. Ninety-five percent of patients underwent 5-fluorouracil-based chemotherapy with oxaliplatin and/or irinotecan. Sixty percent of the patients were categorized as chemotherapy responders (30% reduction in tumor diameter). The DLM had an AUC of 0.77. The AUC for the clinical model was 0.41. CONCLUSIONS: Image-based DLM for prediction of response to neoadjuvant chemotherapy in patients with colorectal cancer liver metastases was superior to a clinical-based model. These results demonstrate potential to identify nonresponders to chemotherapy and guide select patients toward earlier curative resection.

Genes in human obesity loci are causal obesity genes in C. elegans.

Obesity and its associated metabolic syndrome are a leading cause of morbidity and mortality. Given the disease's heavy burden on patients and the healthcare system, there has been increased interest in identifying pharmacological targets for the treatment and prevention of obesity. Towards this end, genome-wide association studies (GWAS) have identified hundreds of human genetic variants associated with obesity. The next challenge is to experimentally define which of these variants are causally linked to obesity, and could therefore become targets for the treatment or prevention of obesity. Here we employ high-throughput in vivo RNAi screening to test for causality 293 C. elegans orthologs of human obesity-candidate genes reported in GWAS. We RNAi screened these 293 genes in C. elegans subject to two different feeding regimens: (1) regular diet, and (2) high-fructose diet, which we developed and present here as an invertebrate model of diet-induced obesity (DIO). We report 14 genes that promote obesity and 3 genes that prevent DIO when silenced in C. elegans. Further, we show that knock-down of the 3 DIO genes not only prevents excessive fat accumulation in primary and ectopic fat depots but also improves the health and extends the lifespan of C. elegans overconsuming fructose. Importantly, the direction of the association between expression variants in these loci and obesity in mice and humans matches the phenotypic outcome of the loss-of-function of the C. elegans ortholog genes, supporting the notion that some of these genes would be causally linked to obesity across phylogeny. Therefore, in addition to defining causality for several genes so far merely correlated with obesity, this study demonstrates the value of model systems compatible with in vivo high-throughput genetic screening to causally link GWAS gene candidates to human diseases.

Management of Pediatric Type III Tibial Shaft Fractures: A Cohort Study Utilizing the Trauma Quality Improvement Program Database.

BACKGROUND: Pediatric open tibial fractures represent a challenging subset of injuries with limited literature to guide management. For children, the epidemiology, management, and outcomes of tibial-shaft fractures have not been fully described. METHODS: A retrospective analysis of the Trauma Quality Improvement Program Data Bank from 2017-2020 was used to query demographics, injury patterns, and management strategies in pediatric open tibial fractures. Fractures were compared by age group (0-5, 6-12, 13-17 years) and type (I/II vs type III). A subgroup analysis was performed on patients with type III open fractures. RESULTS: A total of 3480 open tibial fractures were identified, 3049 were type I/II, and 431 were type III. Motor vehicle accidents (48%) were the most common mechanism of injury (P < 0.001). Subanalysis of 128 type IIIb/c tibial fractures revealed local flap reconstruction (25%) skin graft (25%), and free tissue transfer were the most common management strategies and soft-tissue coverage was achieved after 162 hours (interquartile range = 109-231). Negative pressure wound therapy was utilized in 63% of cases but used in isolation in only 23% of cases. Immediate fixation with intramedullary nailing was more frequently used in the 13-17 age group while plate fixation was more commonly used in younger age groups. CONCLUSIONS: Soft-tissue management patterns following open tibial shaft fractures mirror those seen in adult cohorts. The median time to achieve soft-tissue coverage exceeds the traditional 72-hour target advocated by Godina. Age-based variation is seen in orthopedic management of these fractures based on growth maintenance concerns.

Strength, speed, and anthropometric predictors of in-game batting performance in baseball.

A key focus of sports science research is the identification of quantitative assessments that can predict players' on-field performance and developmental potential. Despite efforts to establish predictive models, there are few validated measures that show reliable associations and large gaps in understanding. Here, we test a multidimensional battery of assessments developed through the USA Baseball, Prospect Development Pipeline that capture strength and functional movement abilities, and anthropometric characteristics, in a two-year cohort of collegiate baseball players from the Appalachian League. Swing propensity metrics for Zone Contact Percentage (ZCP: proportion pitches in strike zone swung at and hit) and Hard-Hit Percentage (HHP: proportion in-play balls with exit velocity ≥ 95 mph) were calculated on 189 players. Models testing hierarchical combinations of anthropometric and anthropometric plus assessment data were implemented using nested cross-validation with random forest and elastic net regression. Results indicate that anthropometric features account for 29% of variance in ZCP and 50-55% of HHP, while the addition of assessment contributed an additional 1-3% to ZCP and 5-12% to HHP, with top predictors coming from PDP strength and power assessments. These findings delineate contributions of andromorphic and physical abilities to in-game baseball performance using a validated assessment battery and advanced game statistics.

Demystifying Velopharyngeal Dysfunction for Plastic Surgery Trainees Part 2: Speech Fundamentals and Perceptual Speech Assessment.

Velopharyngeal dysfunction (VPD) is the inability to achieve proper closure of the velopharyngeal (VP) port, affecting speech and swallowing. The gold standard for diagnosis is auditory-perceptual speech evaluation by a specialized speech-language pathologist. This 3-part series provides a comprehensive discussion on (1) the anatomy and physiology of the velopharyngeal mechanism, (2) fundamental speech terminology and principles of perceptual speech assessment for VPD, and (3) techniques for objective evaluation of the VP port and surgical decision-making process. In part 2, the authros begin with the concepts and terminology required to understand the perceptual speech assessment of VPD, including resonance, articulation, and the differentiation between consonants and vowels. We review the types of speech samples used for evaluation such as single-word articulation tests, syllable repetition, sentence repetition, and spontaneous connected speech. Finally, we discuss the auditory-perceptual speech assessment for VPD, including the assessment of resonance, nasal air emission, articulation, and voice quality. The use of rating scales like the Pittsburgh Weighted Speech Scale (PWSS) and the Cleft Audit Protocol for Speech-Augmented-Americleft Modification (CAPS-A-AM) is highlighted. In addition, the significance of intraoral examinations, visual-tactile-auditory evaluations, and the assessment of voice quality are covered. Most textbook chapters discussing this topic assume a foundational knowledge of speech-language pathology, which a surgical trainee may lack. This study aimed to bridge the gap between surgical training and speech pathology, providing a comprehensive resource to enhance the understanding and management of VPD.

Demystifying Velopharyngeal Dysfunction for Plastic Surgery Trainees-Part 1: Anatomy and Physiology.

The velopharyngeal (VP) port separates the nasopharynx from the oropharynx and is bordered by the velum, lateral pharyngeal walls, and posterior pharyngeal wall. Velopharyngeal dysfunction (VPD) is the inability to achieve proper closure of the VP port, affecting speech and swallowing. This 3-part series provides a comprehensive discussion on (1) the anatomy and physiology of the velopharyngeal mechanism; (2) fundamental speech terminology and principles of perceptual speech assessment for VPD; and (3) techniques for objective evaluation of the VP port and surgical decision-making process. In part 1, the authors focus on the anatomy and physiology of the velopharyngeal port, the anatomy of cleft palate, and the causes of VPD. There are 3 types of VPD: velopharyngeal insufficiency, involving structural deficits; velopharyngeal incompetence, resulting from neuromuscular issues; and velopharyngeal mislearning, due to maladaptive speech habits. VPD is commonly associated with cleft palate due to anatomic disruptions that impair velopharyngeal function. However, there are numerous causes of noncleft VPD, including congenital or acquired structural defects, neuromuscular conditions, and developmental/behavioral factors. Diagnosis and management of VPD require a multidisciplinary approach involving, at a minimum, surgeons and speech-language pathologists. Plastic surgery trainees often receive education on the surgical treatment of VPD, but without a foundational knowledge of the disease spectrum and speech pathology, the complex terminology can impede a thorough understanding of its diagnosis and management. This series serves as an accessible resource, providing the foundational knowledge required for surgical trainees new to this topic.

Demystifying Velopharyngeal Dysfunction for Plastic Surgery Trainees Part 3: Objective Assessment and Surgical Decision-Making.

Velopharyngeal dysfunction (VPD) is the inability to achieve proper closure of the velopharyngeal (VP) port, affecting speech and swallowing. After an auditory-perceptual speech evaluation by a speech-language pathologist, objective assessment of the VP port is required to determine the need for surgical intervention. This 3-part series provides a comprehensive discussion on (1) the anatomy and physiology of the velopharyngeal mechanism; (2) fundamental speech terminology and principles of perceptual speech assessment for VPD; and (3) techniques for objective evaluation of the VP port and surgical decision-making process. In part 3, the authors focus on the modalities for objective VP port assessment, including both direct and indirect methods. Direct imaging techniques such as videofluoroscopy, nasoendoscopy, and MRI are detailed for their strengths and limitations in visualizing VP port function and preoperative planning. Indirect assessments, including nasometry and aerodynamic measurements, are also briefly discussed. The decision-making process for surgical intervention is explored, emphasizing factors such as the severity and etiology of VPD, VP closure patterns, palatal length, orientation of the levator veli palatini, and other patient-specific considerations. The authors review the surgical options for repair including palatoplasty procedures (Furlow palatoplasty, straight-line intravelar veloplasty, and palatal lengthening buccal myomucosal flaps) and pharyngoplasty procedures (posterior pharyngeal flaps and sphincter pharyngoplasty), highlighting their indications, techniques, and potential complications. This series serves as an accessible resource, providing the foundational knowledge required for surgical trainees new to this topic.

Publication Trends and Surgeon Perceptions: A Comprehensive Analysis of Gender Disparities in Craniofacial Surgery.

In academic craniofacial surgery, gender disparities exist across various metrics including faculty positions, leadership roles, and conference representation. This study benchmarks the academic productivity of craniofacial surgeons in 2022 and surveys their perspectives regarding diversity, equity, and inclusion (DEI).Total, first author, and senior author PubMed publications in 2022 were recorded for 193 craniofacial attendings and fellows. Craniofacial surgeons were also surveyed regarding academic experience, leadership roles, and DEI perceptions.Electronic.26 craniofacial attendings.Total, first author, and senior author publication counts in 2022.Women comprised 27% (n = 53) of the craniofacial surgeon cohort. Men led total publications (81% vs 19%, p < 0.001), senior-author publications (84% vs 16%, p < 0.001), average total publications (6.6 vs 4.0, p = 0.043), and average senior-author publications (3.1 vs 1.5, p = 0.02). Sub-analysis of craniofacial fellows showed a higher proportion of women (65%) with no statistical difference in total or average publication counts. Survey responses (n = 26) included a perceived lack of female representation in academic and leadership roles. Barriers included inadequate support from current leadership, systemic issues, and biases. Recommendations for improvement included mentorship programs, targeted recruitment, and equitable conference speaker selection.Ongoing gender disparities are evident in craniofacial surgery, particularly in academic metrics. However, trends in younger cohorts exhibit more balanced gender representation, publication records, and leadership positions, indicating potential improvements. Further studies are needed to examine these cohorts more comprehensively and longitudinally. Sustained commitment, including mentorship programs and enhanced DEI efforts, is needed to continue this progress.

Barriers in Accessing Orthodontic Care for Patients with Orofacial Clefts: Insights from a Florida-Based Survey and National Database Analysis.

OBJECTIVE: To assess the barriers to obtaining care for patients with orofacial clefts through a survey of Florida-based orthodontists and families and an analysis of the Pediatric Health Information System (PHIS) database. DESIGN: A cross-sectional study utilizing multiple-choice questionnaires completed by Florida orthodontists and caregivers of patients who attended a Florida-based cleft and craniofacial clinic. Additionally, data from the PHIS database were analyzed to investigate national factors affecting the age of alveolar bone grafting (ABG). SETTING: Craniofacial team in Florida. PATIENTS/PARTICIPANTS: The survey included 39 orthodontists (7.1% response rate) and 48 caregivers (41% response rate) The PHIS study included 1182 patients. MAIN OUTCOME MEASURES: Barrier to orthodontic care and age of ABG. RESULTS: Orthodontic Survey: Among the surveyed orthodontists, 71% treated cleft/craniofacial patients, 37% accepted Medicaid, and 55% provided pro-bono care. Poor reimbursement was identified as the most common barrier (58%). Caregiver Survey: Most patients were insured by Medicaid (67%), with 55% incurring out-of-pocket expenses. PHIS Database: The average age of ABG was 10.3 years (SD = 3.2). Government funding was associated with a 6.0-month delay in ABG (p = 0.047) and residing in non-Medicaid expanded states was linked to a 6.0-month delay (p = 0.023). Post-Medicaid expansion status was also associated with a delay (p = 0.004). CONCLUSIONS: Access to oral care is difficult for patients with OFC. Despite both federal and state mandates, many financial and non-financial barriers still exist in accessing orthodontic care and a majority of patients experience significant out-of-pocket expenses despite statutorily mandated insurance coverage.

Benzo[a]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or Brussels sprouts.

Utilizing the atto-zeptomole sensitivity of UPLC-accelerator mass spectrometry (UPLC-AMS), we previously demonstrated significant first-pass metabolism following escalating (25-250 ng) oral micro-dosing in humans of [14C]-benzo[a]pyrene ([14C]-BaP). The present study examines the potential for supplementation with Brussels sprouts (BS) or 3,3'-diindolylmethane (DIM) to alter plasma levels of [14C]-BaP and metabolites over a 48-h period following micro-dosing with 50 ng (5.4 nCi) [14C]-BaP. Volunteers were dosed with [14C]-BaP following fourteen days on a cruciferous vegetable restricted diet, or the same diet supplemented for seven days with 50 g of BS or 300 mg of BR-DIM® prior to dosing. BS or DIM reduced total [14C] recovered from plasma by 56-67% relative to non-intervention. Dietary supplementation with DIM markedly increased Tmax and reduced Cmax for [14C]-BaP indicative of slower absorption. Both dietary treatments significantly reduced Cmax values of four downstream BaP metabolites, consistent with delaying BaP absorption. Dietary treatments also appeared to reduce the T1/2 and the plasma AUC(0,∞) for Unknown Metabolite C, indicating some effect in accelerating clearance of this metabolite. Toxicokinetic constants for other metabolites followed the pattern for [14C]-BaP (metabolite profiles remained relatively consistent) and non-compartmental analysis did not indicate other significant alterations. Significant amounts of metabolites in plasma were at the bay region of [14C]-BaP irrespective of treatment. Although the number of subjects and large interindividual variation are limitations of this study, it represents the first human trial showing dietary intervention altering toxicokinetics of a defined dose of a known human carcinogen.

Structural and functional changes in the retina in Parkinson's disease.

Parkinson's disease is caused by degeneration of dopaminergic neurons, originating in the substantia nigra pars compacta and characterised by bradykinesia, rest tremor and rigidity. In addition, visual disorders and retinal abnormalities are often present and can be identified by decreased visual acuity, abnormal spatial contrast sensitivity or even difficulty in complex visual task completion. Because of their early onset in patients with de novo Parkinson's disease, the anatomical retinal changes and electrophysiological modification could be valuable markers even at early stages of the disease. However, due to the concomitant occurrence of normal ageing, the relevance and specificity of these predictive values can be difficult to interpret. This review examines retinal dysfunction arising in Parkinson's disease. We highlight the electrophysiological delays and decreased amplitude in the electroretinography recorded in patients and animal models. We relate this to coexisting anatomical changes such as retinal nerve fibre layer and macular thinning, measured using optical coherence tomography, and show that functional measures are more consistent overall than optical coherence-measured structural changes. We review the underlying chemical changes seen with loss of retinal dopaminergic neurons and the effect of levodopa treatment on the retina in Parkinson's disease. Finally, we consider whether retinal abnormalities in Parkinson's disease could have a role as potential markers of poorer outcomes and help stratify patients at early stages of the disease. We emphasise that retinal measures can be valuable, accessible and cost-effective methods in the early evaluation of Parkinson's disease pathogenesis with potential for patient stratification.

Succinate prodrugs as treatment for acute metabolic crisis during fluoroacetate intoxication in the rat.

Sodium fluoroacetate (FA) is a metabolic poison that systemically inhibits the tricarboxylic acid (TCA) cycle, causing energy deficiency and ultimately multi-organ failure. It poses a significant threat to society because of its high toxicity, potential use as a chemical weapon and lack of effective antidotal therapy. In this study, we investigated cell-permeable succinate prodrugs as potential treatment for acute FA intoxication. We hypothesized that succinate prodrugs would bypass FA-induced mitochondrial dysfunction, provide metabolic support, and prevent metabolic crisis during acute FA intoxication. To test this hypothesis, rats were exposed to FA (0.75 mg/kg) and treated with the succinate prodrug candidate NV354. Treatment efficacy was evaluated based on cardiac and cerebral mitochondrial respiration, mitochondrial content, metabolic profiles and tissue pathology. In the heart, FA increased concentrations of the TCA metabolite citrate (+ 4.2-fold, p < 0.01) and lowered ATP levels (- 1.9-fold, p < 0.001), confirming the inhibition of the TCA cycle by FA. High-resolution respirometry of cardiac mitochondria further revealed an impairment of mitochondrial complex V (CV)-linked metabolism, as evident by a reduced phosphorylation system control ratio (- 41%, p < 0.05). The inhibition of CV-linked metabolism is a novel mechanism of FA cardiac toxicity, which has implications for drug development and which NV354 was unable to counteract at the given dose. In the brain, FA induced the accumulation of ß-hydroxybutyrate (+ 1.4-fold, p < 0.05) and the reduction of mitochondrial complex I (CI)-linked oxidative phosphorylation (OXPHOSCI) (- 20%, p < 0.01), the latter of which was successfully alleviated by NV354. This promising effect of NV354 warrants further investigations to determine its potential neuroprotective effects.

Balancing on a Knife's Edge: Studies on the Synthesis of Pillar[6]arene Derivatives.

Pillar[6]arenes are established as crucial building blocks in supramolecular chemistry; however, they can be difficult to synthesize, particularly in the absence of large solubilizing substituents. In this work, we explore variability in literature syntheses of pillar[6]arene derivatives and suggest that the outcome is dependent on whether oligomeric intermediates stay in solution long enough for the thermodynamically favorable macrocyclization to occur. We demonstrate that in a previously capricious BF3·OEt2-mediated procedure, ≤5 mol % of a Brønsted acid can slow down the reaction to favor macrocycle formation.

Exploring the Excited States of a Hexa-peri-hexabenzocoronene-Substituted Dipyridophenazine Ligand and Its Metal Complexes.

A hexa-peri-hexabenzocoronene (HBC)-substituted dipyridophenazine (dppz) ligand (dppz-HBC) and its corresponding rhenium [Re(CO)3Cl] and ruthenium [Ru(bpy)2]2+ complexes were synthesized and characterized. The interplay of their various excited states was investigated using spectroscopic and computational techniques. Perturbation of the HBC was seen through a broadening and decreased intensity of the HBC absorption bands that dominate the absorption spectra. A delocalized, partial charge transfer state was shown through emission (520 nm) in the ligand and rhenium complex and is supported by time-dependent density functional theory calculations. Transient absorption measurements revealed the presence of dark states with a triplet delocalized state populated in the ligand, while in the complexes, longer-lived (2.3-2.5 µs) triplet HBC states could be accessed. The properties of the studied ligand and complexes provide insight into the future design of polyaromatic systems and add to the rich history of dppz systems.

Siloxane Emissions and Exposures during the Use of Hair Care Products in Buildings.

Cyclic volatile methyl siloxanes (cVMS) are ubiquitous in hair care products (HCPs). cVMS emissions from HCPs are of concern, given the potential adverse impact of siloxanes on the environment and human health. To characterize cVMS emissions and exposures during the use of HCPs, realistic hair care experiments were conducted in a residential building. Siloxane-based HCPs were tested using common hair styling techniques, including straightening, curling, waving, and oiling. VOC concentrations were measured via proton-transfer-reaction time-of-flight mass spectrometry. HCP use drove rapid changes in the chemical composition of the indoor atmosphere. cVMS dominated VOC emissions from HCP use, and decamethylcyclopentasiloxane (D5) contributed the most to cVMS emissions. cVMS emission factors (EFs) during hair care routines ranged from 110-1500 mg/person and were influenced by HCP type, styling tools, operation temperatures, and hair length. The high temperature of styling tools and the high surface area of hair enhanced VOC emissions. Increasing the hair straightener temperature from room temperature to 210 °C increased cVMS EFs by 50-310%. Elevated indoor cVMS concentrations can result in substantial indoor-to-outdoor transport of cVMS via ventilation (0.4-6 tons D5/year in the U.S.); thus, hair care routines may augment the abundance of cVMS in the outdoor atmosphere.

Perceived discrimination and nativity status: risk of cognitive impairment among Latin American older adults.

OBJECTIVES: We examined the association between perceived discrimination and the risk of cognitive impairment with no dementia (CIND) and Alzheimer's disease and related dementias (ADRD) while considering the potential effects of nativity status. DESIGN: A prospective analysis of discrimination and nativity status with dementia and cognitive impairment was conducted among Latinx adults aged 51 years and older who participated in the Health and Retirement Study. SETTING: A national representative sample. PARTICIPANTS: A sample of 1,175 Latinx adults aged 51 years and older. MEASUREMENTS: Demographics, cognitive functioning, perceived discrimination, and nativity status (US-born vs. non-US born) were assessed. Traditional survival analysis methods (Fine and gray models) were used to account for the semi-competing risk of death with up to 10 years of follow-up. RESULTS: According to our results, neither everyday discrimination nor nativity status on their own had a statistically significant association with CIND/ADRD; however, non-US-born Latinx adults who reported no discrimination had a 42% lower risk of CIND/ADRD (SHR = 0.58 [0.41, 0.83], p = .003) than US-born adults. CONCLUSIONS: These results highlight the need for healthcare providers to assess for discrimination and provide support and resources for those experiencing discrimination. It also highlights the need for better policies that address discrimination and reduce health disparities.