Trends in memory function and memory impairment among older adults in the USA and Europe, 1996-2018.

BACKGROUND: Single-country studies document varying time trends in memory function and impairment. Comparative analyses are limited. METHODS: We used self-respondent data on adults aged 50+ years in 13 countries from three surveys (USA: HRS, 1998-2018; England: ELSA, 2002-2018; 11 European countries: SHARE, 2004-2019). Memory is measured with tests of immediate and delayed word recall. Unweighted age- and gender-adjusted mixed effects regression models as well as models with adjustments for additional socio-demographic characteristics and health behaviors were examined. Heterogeneity in trends by gender, age group, and educational attainment were measured. RESULTS: The age-adjusted 10-year improvement in average test score is 0.04 standard deviations (SDs) (95% confidence interval (CI): 0.03, 0.05) in the USA, 0.17 SDs (95% CI: 0.15, 0.19) in England, and 0.24 SDs (95% CI: 0.23, 0.25) in SHARE countries. Trends are largely similar across gender, age groups, and educational attainment. Regional differences in trends remain after adjustment for potential mechanisms. Difference between the USA and other countries is particularly large under aged 75 years compared to over aged 75 years. CONCLUSIONS: Pace of improvement in memory function varies strongly across countries. On average, the 11 European countries studied had the fastest improvement, followed by England. The trend in the USA indicates improvement, but at a much slower pace compared to that in England and other European countries. Uncovering the causes for the cross-country heterogeneity in time trends, and in particular the reasons for the comparatively poor performance of the USA, should be both a research and public health priority.

Proposed Quality Indicators for Aspects of Pediatric Acute Otitis Media Management.

BACKGROUND: The high incidence of pediatric acute otitis media (AOM) makes the implications of overdiagnosis and overtreatment far-reaching. Quality indicators (QIs) for AOM are limited, drawing from generalized upper respiratory infection QIs, or locally developed benchmarks. Recognizing this, we sought to develop pediatric AOM QIs to build a foundation for future quality improvement efforts. METHODS: Candidate indicators (CIs) were extracted from existing guidelines and position statements. The modified RAND Corporation/University of California, Los Angeles (RAND/UCLA) appropriateness methodology was used to select the final QIs by an 11-member expert panel consisting of otolaryngology-head and neck surgeons, a pediatrician and family physician. RESULTS: Twenty-seven CIs were identified after literature review, with an additional CI developed by the expert panel. After the first round of evaluations, the panel agreed on 4 CIs as appropriate QIs. After an expert panel meeting and subsequent second round of evaluations, the panel agreed on 8 final QIs as appropriate measures of high-quality care. The 8 final QIs focus on topics of antimicrobial management, specialty referral, and tympanostomy tube counseling. CONCLUSIONS: Evidence of variable and substandard care persists in the diagnosis and management of pediatric AOM despite the existence of high-quality guidelines. This study proposes 8 QIs which compliment guideline recommendations and are meant to facilitate future quality improvement initiatives that can improve patient outcomes.

The psychosocial impact of prostate cancer screening for BRCA1 and BRCA2 carriers.

OBJECTIVES: To report the long-term outcomes from a longitudinal psychosocial study that forms part of the 'Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted Screening in men at higher genetic risk and controls' (IMPACT) study. The IMPACT study is a multi-national study of targeted prostate cancer (PrCa) screening in individuals with a known germline pathogenic variant (GPV) in either the BReast CAncer gene 1 (BRCA1) or the BReast CAncer gene 2 (BRCA2). SUBJECTS AND METHODS: Participants enrolled in the IMPACT study were invited to complete a psychosocial questionnaire prior to each annual screening visit for a minimum of 5 years. The questionnaire included questions on sociodemographics and the following measures: Hospital Anxiety and Depression Scale, Impact of Event Scale, 36-item Short-Form Health Survey, Memorial Anxiety Scale for PrCa, Cancer Worry Scale, risk perception and knowledge. RESULTS: A total of 760 participants completed questionnaires: 207 participants with GPV in BRCA1, 265 with GPV in BRCA2 and 288 controls (non-carriers from families with a known GPV). We found no evidence of clinically concerning levels of general or cancer-specific distress or poor health-related quality of life in the cohort as a whole. Individuals in the control group had significantly less worry about PrCa compared with the carriers; however, all mean scores were low and within reported general population norms, where available. BRCA2 carriers with previously high prostate-specific antigen (PSA) levels experience a small but significant increase in PrCa anxiety (P = 0.01) and PSA-specific anxiety (P < 0.001). Cancer risk perceptions reflected information provided during genetic counselling and participants had good levels of knowledge, although this declined over time. CONCLUSION: This is the first study to report the longitudinal psychosocial impact of a targeted PrCa screening programme for BRCA1 and BRCA2 carriers. The results reassure that an annual PSA-based screening programme does not have an adverse impact on psychosocial health or health-related quality of life in these higher-risk individuals. These results are important as more PrCa screening is targeted to higher-risk groups.

"A lonely time for deaf and hard of hearing kids": A qualitative study of the impact of pandemic precautions on classroom communication for adolescents with hearing loss.

BACKGROUND: Pandemic public health measures, such as masks and social distancing, present unique challenges for people who are hard-of-hearing. This study sought to understand how adolescents with varying levels of hearing loss would describe their experiences communicating in a classroom environment during a pandemic and its associated public health measures. METHODS: Qualitative study utilizing one-on-one semi-structured interviews conducted from July 2021 to April 2022. Interviews were transcribed and analyzed using a reflexive thematic analysis to conceptualize the main themes from the data. Adolescents ages 12-17 who attended school in person during the COVID-19 pandemic with either normal hearing or; bilateral cochlear implants or; bone-anchored hearing aids or; unilateral moderate to severe (40-70 dB) conductive hearing loss secondary to mastoidectomy, were interviewed. Participants were recruited from BC Children's Hospital Otolaryngology clinic via a convenience sample. RESULTS: Fourteen adolescents were interviewed with a median age of 15, 9 with hearing loss and 5 with normal hearing. Pandemic associated challenges such as masks muffling speech, protocol fatigue, and missing pre-pandemic life were present in both the hearing loss and normal hearing groups. Classroom communication for adolescents with hearing loss was disproportionately affected by pandemic measures, leading to challenges making friends, feeling behind their peers in learning, and listening fatigue. Resilience was noted among adolescents with hearing loss in their ability to adapt to pandemic measures and changing classroom dynamics. For adolescents with unilateral hearing loss, the pandemic provided an improved listening environment via a reduction in background noise. CONCLUSION: Pre-existing classroom communication challenges for adolescents with hearing loss were amplified under pandemic public health measures and shared, in part, by those with normal hearing. These findings can be used to further inform classroom design to the optimize learning environment for deaf and hard of hearing students.

Spatiotemporal Organization of Prefrontal Norepinephrine Influences Neuronal Activity.

Norepinephrine (NE), a neuromodulator released by locus ceruleus (LC) neurons throughout the cortex, influences arousal and learning through extrasynaptic vesicle exocytosis. While NE within cortical regions has been viewed as a homogenous field, recent studies have demonstrated heterogeneous axonal dynamics and advances in GPCR-based fluorescent sensors permit direct observation of the local dynamics of NE at cellular scale. To investigate how the spatiotemporal dynamics of NE release in the prefrontal cortex (PFC) affect neuronal firing, we employed in vivo two-photon imaging of layer 2/3 of the PFC in order to observe fine-scale neuronal calcium and NE dynamics concurrently. In this proof of principle study, we found that local and global NE fields can decouple from one another, providing a substrate for local NE spatiotemporal activity patterns. Optic flow analysis revealed putative release and reuptake events which can occur at the same location, albeit at different times, indicating the potential to create a heterogeneous NE field. Utilizing generalized linear models, we demonstrated that cellular Ca2+ fluctuations are influenced by both the local and global NE field. However, during periods of local/global NE field decoupling, the local field drives cell firing dynamics rather than the global field. These findings underscore the significance of localized, phasic NE fluctuations for structuring cell firing, which may provide local neuromodulatory control of cortical activity.

Total Synthesis of Lissodendoric Acid A.

We describe a full account of our synthetic strategy leading to the first total synthesis of the manzamine alkaloid lissodendoric acid A . These efforts demonstrate that strained cyclic allenes are valuable synthetic building blocks and can be employed efficiently in total synthesis.

Access to Complex Scaffolds Through [2 + 2] Cycloadditions of Strained Cyclic Allenes.

We report the strain-induced [2 + 2] cycloadditions of cyclic allenes for the assembly of highly substituted cyclobutanes. By judicious choice of trapping agent, complex scaffolds bearing heteroatoms, fused rings, contiguous stereocenters, spirocycles, and quaternary centers are ultimately accessible. Moreover, we show that the resulting cycloadducts can undergo thermal isomerization. This study provides an alternative strategy to photochemical [2 + 2] cycloadditions for accessing highly functionalized cyclobutanes, while validating the use of underexplored strained intermediates for the assembly of complex architectures.

Medical student challenges in the wake of integrated interventional radiology residency: A review.

Interventional radiology is a new medical specialty that recently created an integrated residency. This study serves a comprehensive review of literature discussing the challenges that medical students encounter in light of this new pathway, with a specific emphasis on the virtual application process. An analysis of 24 articles revealed that exposure to interventional radiology in medical school is lacking, with a limited pool of diverse mentors in the field. Moreover, medical school advising to students applying to interventional radiology may be inadequate. Although initiatives have been successful in increasing exposure, and there is encouraging data on diversity in the field at the trainee level since the start of the integrated residency, addressing the needs of medical students and focusing on the gaps in mentorship, advising, and curriculum is crucial for the success of applicants and overall specialty recruitment. The virtual process has provided on average $6008 of savings for applicants.

Radiopharmaceuticals for Cancer Diagnosis and Therapy: New Targets, New Therapies-Alpha-Emitters, Novel Targets.

ABSTRACT: Radiopharmaceutical therapy has emerged as a promising approach for the treatment of various cancers. The exploration of novel targets such as tumor-specific antigens, overexpressed receptors, and intracellular biomolecules using antibodies, peptides, or small molecules has expanded the scope of radiopharmaceutical therapy, enabling precise and effective cancer treatment for an increasing number of tumor types. Alpha emitters, characterized by their high linear energy transfer and short path length, offer unique advantages in targeted therapy due to their potent cytotoxicity against cancer cells while sparing healthy tissues. This article reviews recent advancements in identifying novel targets for radiopharmaceutical therapy and applications in utilizing α-emitters for targeted treatment.

Factors Associated With and Characteristics of Patients Receiving Proton Therapy at the End of Life.

Purpose: To identify the characteristics, indications, and toxicities among patients receiving proton beam therapy (PBT) in the final year of life at an academic medical center. Materials and Methods: A retrospective review of patients who received PBT within the final 12 months of life was performed. Electronic medical records were reviewed for patient and treatment details from 2010 to 2019. Patients were followed from the start of PBT until death or last follow-up. Acute (3 months) toxicities were graded using the Common Terminology Criteria for Adverse Events v5.0. Imaging response was assessed using the Response Evaluation Criteria in Solid Tumors v1.1. The χ2 test was used to evaluate factors associated with palliative treatment. Simple logistic regression was used to evaluate factors associated with toxicity. Results: Bet299 patients were treated at the end of life (EOL) out of 5802 total patients treated with PBT (5.2%). Median age was 68 years (19-94 years), 58% male. The most common cancer was nonsmall cell lung cancer (27%). Patients were treated for symptom palliation alone (11%), durable control (57%), curative intent (16%), local recurrence (14%), or oligometastatic disease (2%). Forty-five percent received reirradiation. Median treatment time was 32 days (1-189 days). Acute toxicity was noted in 85% of the patients (31% G1, 53% G2, 15% G3). Thirteen patients (4%) experienced chronic toxicity. Breast and hematologic malignancy were associated with palliative intent χ2 (1, N = 14) = 17, P = .013; (χ2 (1, N = 14) = 18, P = .009). Conclusion: The number of patients treated with PBT at the EOL was low compared to all comers. Many of these patients received treatment with definitive doses and concurrent systemic therapy. Some patients spent a large portion of their remaining days on treatment. A prognostic indicator may better optimize patient selection for PBT at the EOL.

A systematic review of stage IVA cervical cancer treatment: Challenges in the management of an understudied group.

OBJECTIVE: Stage IVA patients comprise a small proportion of participants in cervical cancer trials, yet survival outcomes are disproportionately poor. We aim to perform a systematic review evaluating stage IVA cervical cancer. METHODS: This systematic review was completed via PRISMA 2020 guidelines using two databases. Inclusion criteria comprised Phase III trials (2004-2024) assessing stage IVA cervical cancer including patients by stage. Searches had MeSH terms: ((cervical cancer) AND (stage IVA) AND (locally advanced)). 761 were articles identified, including books, trials, reviews, and meta-analyses. Of the articles identified, 12 met inclusion criteria. RESULTS: A total of 133 (3.8% of study populations) stage IVA and 818 (40% of study populations) stage III-IVA cervical cancer patients were analyzed. Two studies (stage IVA n = 15; 3.1%) established cisplatin as chemoradiotherapy agent of choice, while one study (stage IVA n = 2; 1%) showed no benefit with cisplatin versus radiotherapy alone. Four studies (stage IVA n = 32; 3.6%; stages IIIB-IVA n = 220; 24%) found no benefit with adjuvant chemotherapy, with one analyzing stage IIIB-IVA patients (progression-free survival (PFS) hazard ratio (HR) = 0.84; 95% confidence interval (CI): 0.57-1.23). Three studies (stage IVA n = 71; 5%) found no benefit adding immunomodulator (stage IVA overall survival HR = 3.48; 95% CI: 0.52-23.29), hypoxic cell sensitizer, or immunotherapy (stage III-IVA PFS HR = 0.71; 95% CI: 0.49-1.03) to chemoradiotherapy. One study (stages III-IVA n = 598; 56%) found benefit adding immunotherapy to chemoradiotherapy (stage III-IVA PFS HR = 0.58; 95% CI: 0.42-0.8). One study (stage IVA n = 13; 3.5%) showed benefit with induction chemotherapy. CONCLUSION: Trials have not included substantial IVA patients to draw reasonable conclusions. Despite mixed results for immunotherapy, adjuvant chemotherapy, and induction chemotherapy, the exact benefit for stage IVA patients remains unknown. Future clinical trials should include a greater number of stage IVA cervical cancer patients and analyze them individually.

Safety and efficacy of three-dimensional versus two-dimensional endoscopy in otolaryngology surgery and training: A systematic review.

OBJECTIVE: Three-dimensional (3D) endoscopy has been developed to provide depth perception to allow for improved visualisation during otolaryngology surgery. We conducted a systematic review to determine the surgical safety and efficacy of 3D endoscopy in comparison to two-dimensional (2D) endoscopy in performing otolaryngology procedures, and the role of 3D endoscopy as a training tool for novice otolaryngology surgeons. METHODS: Primary studies were identified through MEDLINE, Embase and Web of Science databases, which were searched for articles published through June 2022 that compared the outcomes of 2D and 3D endoscopy in otolaryngology surgical procedures or otolaryngology-relevant simulations. Candidate articles were independently reviewed by two authors. RESULTS: A total of 18 full-text articles met inclusion criteria for this study. In clinical trials (n = 8 studies, 362 subjects), there were no significant differences in performance time, intraoperative or postoperative complications with 3D endoscopes when compared to 2D. In simulation studies (n = 10 studies, 336 participants), 3D endoscopes demonstrated a decreased error rate (n = 5 studies) and shorter performance time (n = 3 studies). Studies also reported improved depth perception (n = 14 studies) and visualisation preference (n = 5 studies) with 3D over 2D systems. The 3D systems were found to have a shorter learning curve and better manoeuvrability among novice surgeons. CONCLUSION: 3D endoscopy showed equivalent safety and efficacy compared to 2D endoscopy in otolaryngology surgery. The improved depth perception and performance for novices using 3D endoscopes suggests the technology may be superior to 2D endoscopes as a training tool for otolaryngology surgeons.

Diabetes Disparities in the United States: Trends by Educational Attainment from 2001 to 2020.

INTRODUCTION: Tracking changes in socioeconomic disparities in diabetes in the U.S. is important to evaluate progress in health equity and guide prevention efforts. Disparities in diabetes prevalence by educational attainment from 2001 to 2020 were investigated. METHODS: Using a serial cross-sectional design, data from 33,220 adults aged 30-79 assessed in nine rounds of the National Health and Nutrition Examination Surveys between 2001 and 2020 were analyzed in 2023-2024. Diabetes was defined as self-reported prior diagnosis, elevated glycated hemoglobin (HbA1c≥6.5%), or use of diabetes medications. Marginalized age- and covariate-adjusted prevalence differences (PD) and prevalence ratios (PR) of diabetes by educational attainment (less than high school graduation, high school graduation, some college education or associate degree, or college graduation [reference]) by calendar period (2001-2004, 2005-2008, 2009-2012, 2013-2016, 2017-2020) were derived from logistic regression models. RESULTS: From 2001 to 2020, age-adjusted diabetes prevalence was consistently higher among adults without a college degree. Adults without a high school diploma exhibited the largest disparities in both 2001-2004 (PD 8.0%; 95%CI 5.6-10.5 and PR 2.1; 95%CI 1.5-2.6) and 2017-20 (PD 11.0%; 95%CI 6.7-15.2 and PR 2.1; 95%CI 1.5-2.7). Between 2001-2004 and 2017-2020, the absolute disparity in diabetes changed only among adults with a high school diploma (increase from PD 1.7%; 95%CI -0.5- 3.9 to PD 8.8% 95%CI 4.1-13.4, respectively), while the PR did not change in any group. Education-related disparities in diabetes were attenuated after accounting for socio-demographic factors and BMI. CONCLUSIONS: From 2001 to 2020, national education-related disparities in diabetes prevalence have shown no signs of narrowing.

Osteochondral Lesions of the Talus: Etiology, Clinical Presentation, Treatment Options, and Outcomes.

This article reviews the etiology, clinical presentation, classification schemes, and treatment options for osteochondral lesions of the talus. These lesions typically occur after a traumatic injury and are best diagnosed on MRI. Asymptomatic lesions and incidentally found lesions are best treated conservatively; however, acute displaced osteochondral fragments may require surgical treatment. Lesion characteristics may dictate surgical technique. Outcomes following surgical treatment may be impacted by patient age, BMI, and lesion characteristics.

Management of Dry Eye Toxicity After Treatment With 177Lu-PSMA-617 Radioligand Therapy.

Treatment options for patients with metastatic castration-resistant prostate cancer include use of radioligand therapy with 177Lu-PSMA-617. 177Lu-PSMA-617 is used to target prostate cancer cells selectively by targeting prostate specific membrane antigen (PSMA); however, PSMA is also expressed on lacrimal glands among other tissues. Herein, we report on a case of a Common Terminology Criteria for Adverse Events version 5 grade 3 dry eye event with concomitant blepharitis after administration of 177Lu-PSMA-617. The patient was managed with neomycin-polymyxin-dexamethasone 3.5-10000-0.1 ophthalmic suspension, artificial tears, lubricating ointments, lid scrubs, and oral antihistamines.

Carbon savings potential of virtual care in obstructive sleep apnea and otitis media with effusion.

Objective: To determine the carbon savings potential of incorporating virtual care into surgical care pathways for pediatric patients with obstructive sleep apnea or otitis media with effusion. Methods: Pediatric patients with obstructive sleep apnea or otitis media with effusion were not enrolled, instead, a modeling cohort study design was used. This study utilized the British Columbia healthcare system and geography to model emissions. Care pathways were developed for pediatric patients with obstructive sleep apnea or otitis media with effusion requiring care at a tertiary pediatric center. Home addresses were located at the geographical center of the two most populated municipalities within each of the 10 most populated regional districts in 2020. Virtual visits replaced up to three clinically equivalent in-person visits. Emissions (kgCO2e) for transport and virtual visits were estimated. Population-weighted means and descriptive statistics were calculated. Results: Utilizing 1, 2, or 3 virtual visits in the obstructive sleep apnea care pathway yielded potential emissions savings of 19.9%, 39.9%, and 59.8% respectively. Integrating 1, 2, or 3 virtual visits into the otitis media with effusion care pathway produced potential emissions savings of 16.6%, 33.2%, and 49.7%, respectively. Integrating 3 virtual visits can save up to 2156.8 kgCO2e per patient. Conclusions: Appropriately conducting up to 50% of clinical encounters virtually for children with obstructive sleep apnea or otitis media with effusion reduced theoretical carbon emissions. For a single child, emission savings could reach over 2150 kgCO2e. Level of Evidence: Level 5.

Generation and reactivity of unsymmetrical strained heterocyclic allenes.

Strained cyclic allenes are short-lived intermediates that confine a functional group with a preferred linear geometry, an allene, into a small ring, inducing strain-driven reactivity. Nitrogen-containing variants, or azacyclic allenes, have proved valuable for the assembly of complex nitrogen-containing compounds. Whereas 3,4-azacyclic allenes, which bear a symmetrical core, have been the focus of multiple studies, their unsymmetrical 2,3-azacyclic counterparts have remained underexplored. In the present study, we report density functional theory studies investigating the structure of such unsymmetrical azacyclic allenes and experimental efforts to access and engage them in strain-promoted cycloadditions under mild conditions. Control experiments support either concerted or stepwise diradical mechanisms for these reactions, depending on the type of cycloaddition examined. Moreover, we generate the corresponding 2,3-oxacyclic allene and demonstrate its reactivity in cycloadditions and a metal-catalysed process. Given the scaffolds accessed, coupled with the observed selectivity trends, these results are expected to encourage the application of unsymmetrical heterocyclic allenes for the synthesis of heterocycles that bear a high fraction of sp3-hybridized atoms.

Clarifying mechanisms and kinetics of programmable catalysis.

Programmable catalysis-the purposeful oscillation of catalytic potential energy surfaces (PES)-has emerged as a promising method for the acceleration of catalyzed reaction rates. However, theoretical study of programmable catalysis has been limited by onerous computational demands of integrating the stiff differential equations that describe periodic cycling between PESs. This work details methods that reduce the computational cost of finding the limit cycle by ≳108×. These methods produce closed-form analytical solutions for didactic case studies, examination of which provides physical insights of programmable catalysis mechanisms. Generalization of these analyses to more complex reaction networks, including CO oxidation on Pt (111) surfaces, exposes the key catalyst properties required to achieve enhanced rates and conversions via one of two programmable catalysis mechanisms: quasi-static (high frequency) and stepwise (intermediate frequency). Analytical description of each mechanism is critical in understanding the consequences of the Sabatier principle on achievable rate enhancement through programmed catalysis.