Associations of Serum Insulin and Related Measures With Neuropathology and Cognition in Older Persons With and Without Diabetes.

OBJECTIVE: To examine associations of serum insulin and related measures with neuropathology and cognition in older persons. METHODS: We studied 192 older persons (96 with diabetes and 96 without, matched by sex and balanced by age-at-death, education, and postmortem interval) from a community-based, clinical-pathologic study of aging, with annual evaluations including neuropsychological testing (summarized into global cognition and 5 cognitive domains) and postmortem autopsy. We assessed serum insulin, glucose, leptin, adiponectin, hemoglobin A1C, advanced glycation-end products (AGEs), and receptors for advanced glycation-end products, and calculated the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and adiponectin-to-leptin ratio. Using adjusted regression analyses, we examined the associations of serum measures with neuropathology of cerebrovascular disease and Alzheimer's disease, and with the level of cognition proximate-to-death. RESULTS: Higher HOMA-IR was associated with the presence of brain infarcts and specifically microinfarcts, and higher HOMA-IR and leptin were each associated with subcortical infarcts. Further, higher leptin levels and lower adiponectin-to-leptin ratios were associated with the presence of moderate-to-severe atherosclerosis. Serum insulin and related measures were not associated with the level of Alzheimer's disease pathology, as assessed by global, as well as amyloid burden or tau tangle density scores. Regarding cognitive outcomes, higher insulin and leptin levels, and lower adiponectin and receptors for advanced glycation-end products levels, respectively, were each associated with lower levels of global cognition. INTERPRETATION: Peripheral insulin resistance indicated by HOMA-IR and related serum measures was associated with a greater burden of cerebrovascular neuropathology and lower cognition. ANN NEUROL 2024;95:665-676.

Hispanic individuals' cervical cancer screening disparities amidst the COVID-19 pandemic.

OBJECTIVE: To examine the impact of the COVID-19 pandemic on cervical cancer screening rates of Hispanic individuals compared to non-Hispanic White (NHW) individuals in the United States, whether a responsive surge in catch-up screenings occurred as society adapted to pandemic changes, and to investigate the sociodemographic characteristics between the study populations. METHODS: Using cross-sectional data from the All of Us Research Program, which incorporates electronic health record data and survey data from a demographically, geographically, and medically diverse participant group, we assessed the annual cervical cancer screening rates during 2019-2021 by race/ethnicity among eligible individuals ages 21-64. RESULTS: Among 116,052 unique individuals (78,829 NHW and 37,223 Hispanic), Hispanic individuals had lower annual cervical cancer screening rates than NHWI across the three years studied. They experienced a more significant decrease in screening from 2019 to 2020 (39.27 %) compared to NHWIs (21.15 %) and less of a rebound increase in the following year, 2021 (10.33 % vs 13.83 %). Hispanic individuals aged 50-64 experienced the sharpest decline in screening rates (-43.01 % from 2019 to 2020). Hispanic individuals also experienced greater adverse social conditions, including lack of insurance or employment, lower educational attainment, and lower household income. CONCLUSIONS: Hispanic individuals experienced a more significant decrease in cervical cancer screening rates with the onset of the COVID-19 pandemic compared with NHW individuals and did not experience a robust rebound in cervical cancer screening rates in 2021. As a result, the disparity in cervical cancer screening rates between NHW and Hispanic individuals considerably worsened with the COVID-19 pandemic.

Low expression of exosomal miR-150 predicts poor prognosis in colorectal cancer patients after surgical resections.

Liver metastasis is a leading indicator of poor prognosis in patients with colorectal cancer (CRC). Exosomal intercellular communication has been reported to play an important role in cancer invasion and metastasis. Here, we characterized exosomal miRNAs underlying liver metastasis in CRC patients (Cohort 1, n = 30) using miRNA arrays. Exosomal miR-150 was found to be downregulated in CRC patients with liver metastases compared to those without (P = 0.025, fold change [FC] = 2.01). These results were then validated using another independent cohort of CRC patients (Cohort 2, n = 64). Patients with low expression of exosomal miR-150 had significantly shorter overall survival (OS) time (33.3 months versus 43.3 months, P = 0.002). In addition, the low expression of exosomal miR-150 was significantly correlated with advanced tumor node metastasis staging (P = 0.013), higher CA199 level (P = 0.018), and the presence of liver metastasis (P = 0.048). Multivariate analysis showed that low expression of exosomal miR-150 (P = 0.035) and liver metastasis (P < 0.001) were independent prognostic factors for overall survival. In vivo and in vitro studies showed that the viability and invasion of CRC cells were both significantly suppressed by ExomiR-150. Target-prediction assessment and dual-luciferase reporter assay indicated that FTO (the fat mass and obesity-associated gene) was a direct target for miR-150. This study first demonstrated that exosomal miR-150 may be a potential prognostic factor and treatment target for CRC.

Spatial and Frequency Specific Artifact Reduction in Optically Pumped Magnetometer Recordings.

BACKGROUND: Magnetoencephalography (MEG) based on optically pumped magnetometers (OPMs) opens up new opportunities for brain research. However, OPM recordings are associated with artifacts. We describe a new artifact reduction method, frequency specific signal space classification (FSSSC), to improve the signal-to-noise ratio of OPM recordings. METHODS: FSSSC was based on time-frequency analysis and signal space classification (SSC). SSC was accomplished by computing the orthogonality of the brain signal and artifact. A dipole phantom was used to determine if the method could remove artifacts and improve accuracy of source localization. Auditory evoked magnetic fields (AEFs) from human subjects were used to assess the usefulness of artifact reduction in the study of brain function because bilateral AEFs have proven a good benchmark for testing new methods. OPM data from empty room recordings were used to estimate magnetic artifacts. The effectiveness of FSSSC was assessed in waveforms, spectrograms, and covariance domains. RESULTS: MEG recordings from phantom tests show that FSSSC can remove artifacts, normalize waveforms, and significantly improve source localization accuracy. MEG signals from human subjects show that FSSC can reveal auditory evoked magnetic responses overshadowed and distorted by artifacts. The present study demonstrates FSSSC is effective at removing artifacts in OPM recordings. This can facilitate the analyses of waveforms, spectrograms, and covariance. The accuracy of source localization of OPM recordings can be significantly improved by FSSSC. CONCLUSIONS: Brain responses distorted by artifacts can be restored. The results of the present study strongly support that artifact reduction is very important in order for OPMs to become a viable alternative to conventional MEG.

Delirium Among Hospitalized Older Adults With Acute Heart Failure Exacerbation.

BACKGROUND: Delirium among older adults hospitalized with acute heart failure is associated with increased mortality. However, studies concomitantly assessing the association of delirium with both clinical and economic outcomes in this population, such as mortality, hospital cost, or length of stay, are lacking. METHODS AND RESULTS: We conducted a retrospective observational study using National Inpatient Sample data from 2011 to 2014. Using multivariable logistic regression, we assessed the association of delirium with in-hospital mortality, then estimated the incremental hospital cost and excessive length of stay adjusting for demographic and clinical factors using multivariable generalized linear regression. The association of other medical complications on clinical and economic outcomes was also assessed. A total of 568,565 (weighted N = 2,826,131) hospitalizations of patients 65 years or older with acute heart failure from 2011 to 2014 were included in the final analysis. The reported prevalence of delirium was 4.53%. After multivariable adjustment, delirium was associated with a 2.35-fold increase in the odds of in-hospital mortality (95% confidence interval [CI] 2.23-2.47), which was lower than the odds ratio for sepsis/septicemia (5.36; 95% CI, 5.02-5.72) or respiratory failure (4.53; 95% CI, 4.38-4.69), but similar to that for acute kidney injury (2.39; 95% CI, 2.31-2.48) and higher than for non-ST elevation myocardial infarct (1.57; 95% CI, 1.46-1.68). Delirium increased the total hospital cost by $4,262 (95% CI, $4,002-4,521) and the length of stay by 1.73 days (95% CI, 1.68-1.78), which was slightly lower than, but similar to, acute kidney injury ($4,771; 95% CI, $4,644-4,897) and 1.82 days (95% CI, 1.79-1.84), and higher than non-ST elevation myocardial infarct ($1,907; 95% CI, $1,629-2,185) and 0.31 days (95% CI, 0.25-0.37). CONCLUSIONS: Delirium was associated with increased in-hospital mortality, total hospital cost, and length of stay, and the magnitude of the effect was similar to that for acute kidney injury. Enhanced efforts to prevent delirium are needed to decrease its adverse impact on clinical and economic outcomes for hospitalized older adults with acute heart failure.

Provider-Patient Discussions About Smoking and the Impact of Lung Cancer Screening Guidelines: NHIS 2011-2015.

BACKGROUND: Clinical practice guidelines for treating tobacco use and lung cancer screening guidelines recommend smoking cessation counseling to current smokers by health care professionals. OBJECTIVE: Our objective was to determine the contemporary patterns of current smokers' discussions about smoking with their health care professionals in the USA. DESIGN, SETTING, AND PARTICIPANTS: We conducted an observational study of 30,132 current smokers (weighted sample 40,126,006) for the years 2011 to 2015 using data from the National Health Interview Survey. MAIN MEASURES: Our main outcome was the proportion of current smokers who had discussions about smoking with their health care professionals. We used the Cochran-Armitage trend test to evaluate the temporal trends in current smokers' discussions about smoking, and used a multivariable logistic model to determine the predictors of discussions about smoking, controlling for smokers' demographics, health status, and receipts of lung cancer screening. KEY RESULTS: Our study found the proportion of current smokers who had discussions about smoking with their health care professionals increased from 51.3% in 2011 to 55.4% in 2015 (P-trend < 0.0001). However, about 15% of current smokers who underwent lung cancer screening did not have or could not recall discussions about smoking with their health care professionals. In multivariable analyses and sensitivity analysis, the predictors of discussions about smoking were being a heavy smoker, receipt of lung cancer screening, being non-Hispanic white, having a physician office visit in the past year, being diagnosed with respiratory conditions, having fair or poor health, and having insurance coverage. CONCLUSIONS: The results demonstrated a steady but slow increase in current smokers' discussions about smoking with their health care professionals in recent years, especially among heavy smokers. More than 40% of current smokers did not have or could not recall any discussions about smoking with their health care professionals.

The evaluation of comprehensive medication management for chronic diseases in primary care clinics, a Texas delivery system reform incentive payment program.

BACKGROUND: The Institute of Medicine reported that more than 1.5 million preventable adverse drug events occur annually in the United States. Comprehensive Medication Management (CMM) is the medication review process to improve clinical outcomes, enhance patient adherence, reduce drug therapy problems and reduce health care costs. University of Texas (UT) Physicians implemented a CMM program in several community-based clinics. We evaluated the effectiveness of CMM to reduce drug therapy problems and achieve medical cost savings. METHODS: This was a retrospective, observational study of CMM participants from October 2015 to September 2016. Program participants included patients aged 18 years or older who had taken more than 4 prescribed medications and were diagnosed with at least one of the following chronic diseases: hypertension, congestive heart failure, chronic obstructive pulmonary disease, asthma or diabetes. Under the CMM program, a clinical pharmacist reviewed patients' electronic health records and created action plans to resolve identified drug problems. As part of the evaluation of the clinical process, two independent physicians conducted peer review on the recommendations issued by the pharmacist in order to establish inter-rater reliability of drug therapy problems and potential consequent medical services. The drug therapy problems were identified and classified into four categories: indication, effectiveness, safety and/or compliance. The average cost of avoided medical services was obtained based on cost extrapolations from the literature, combined with hospital discharge data. Potential medical services avoided were linked to the average cost of those services to calculate the total cost savings of the program from the payers' perspective. RESULTS: By reviewing electronic health records of 3280 patients, the pharmacist identified 301 drug therapy problems and resolved 49.8% of these problems with collaboration from the patient's primary care physician or care team. The most commonly identified drug problems were related to potentially adverse drug reactions or inappropriate drug dosage. The CMM program resulted in potential cost savings of $1,143,015. CONCLUSIONS: The CMM program resolved medication therapy problems among program participants and achieved significant health care cost savings.

LncRNA UCA1/miR-124 axis modulates TGFß1-induced epithelial-mesenchymal transition and invasion of tongue cancer cells through JAG1/Notch signaling.

Tongue cancer remains a massive threat to public health due to the high rate of metastasis. Tumor cell epithelial-mesenchymal transition (EMT), which can be induced by transforming growth factor ß1 (TGFß1), has been regarded as a significant contributor to cancer invasion and migration. In our previous study, long noncoding RNA (lncRNA) MALAT1/miR-124/JAG1 axis modulates the growth of tongue cancer. In addition to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), another lncRNA, urothelial cancer associated 1 (UCA1), can promote EMT and cancer metastasis. In the present study, UCA1 was overexpressed in tongue cancer tissues and cell lines. UCA1 overexpression was correlated to the poorer prognosis of patients with tongue cancer. UCA1 knockdown significantly suppressed TGFß1-induced tongue cancer cell invasion and EMT by decreasing vimentin and increasing E-cadherin. Regarding the molecular mechanism, UCA1 could directly bind to microRNA-124 (miR-124) and negatively regulate each other. UCA1 knockdown ameliorated, whereas miR-124 inhibition exacerbated TGFß1-induced EMT and invasion in tongue cancer cells through miR-124 downstream jagged 1 (JAG1) and Notch signaling. Moreover, miR-124 inhibition partially impaired the effect of UCA1 knockdown. In tongue cancer tissues, miR-124 expression was remarkably decreased, whereas JAG1 mRNA expression was increased. miR-124 was negatively correlated with UCA1 and JAG1. UCA1 and JAG1 were positively correlated. In summary, we provided a novel mechanism by which the EMT process and cancer cell invasion in tongue cancer could be modulated from the perspective of lncRNA-miRNA-mRNA regulation.

Comparative Effectiveness of Computed Tomography- Versus Ultrasound-Guided Percutaneous Radiofrequency Ablation Among Medicare Patients 65 Years of Age or Older With Hepatocellular Carcinoma.

BACKGROUND: For patients with hepatocellular carcinoma (HCC) not eligible for surgical resection, radiofrequency ablation (RFA) is a promising technique that reduces the risk of disease progression. OBJECTIVES: To evaluate whether the trend of image guidance for RFA is moving toward the more expensive computed tomography (CT) technology and to determine the clinical benefits of CT guidance over the ultrasound (US) guidance. METHODS: A cohort of 463 patients was identified from the Surveillance, Epidemiology, and End Results and Medicare-linked database. The temporal trends in use of image guidance were assessed using the Cochrane-Armitage test. The associations between modality of image guidance and survival, complications, and costs were assessed using the Cox regression model, the logistic regression model, and the generalized linear model, respectively. RESULTS: The use of CT-guided RFA increased sharply, from 20.7% in 2002 to 75.9% in 2011. Compared with CT-guided RFA, those who received US-guided RFA had comparable risk of periprocedural and delayed postprocedural complications. Stratified analyses by tumor size also showed no statistically significant difference. In adjusted survival analysis, no statistically significant difference was observed in overall and cancer-specific survival. Nevertheless, the cost of CT-guided RFA ($2847) was higher than that of US-guided RFA ($1862). CONCLUSIONS: Despite its rapid adoption over time, CT-guided RFA incurred higher procedural costs than US-guided RFA but did not significantly improve postprocedural complications and survival. Echoing the American Board of Internal Medicine's Choosing Wisely campaign and the American Society of Clinical Oncology's Value of Cancer Care initiative, findings from our study call for critical evaluation of whether CT-guided RFA provides high-value care for patients with HCC.

Hierarchical Self-Assembly and Chiroptical Studies of Luminescent 4d-4f Cages.

Multinuclear lanthanide-containing supramolecular cages have received increasing attention recently because of their unique electroptical and magnetic properties. Here we report the hierarchical self-assembly and chiroptical studies of a group of 4d-4f heterometallic cages synthesized from a preformed dimetalloligand [(bpy)2Pd212]2+ (2) (bpy = 2,2-bipyridine) and a variety of trivalent lanthanide ions (Ln = NdIII, EuIII, YbIII). The programmable self-assembly process leading to the trigonal bipyramidal cages formulated as {Ln2[(bpy)2Pd212]3}12+ (3) has been confirmed by one- and two-dimensional NMR, electro-spray-ionization time-of-flight mass-spectroscopy, and in one typical case by single-crystal X-ray diffraction studies. Circular dichroism and circular polarized luminescence spectra confirmed the strict control of stereoselectivity on the heterometallic cages, dictated by the chiral amide groups on the ligands. Excitation (up to 420 nm) on the dipalladium chromophores on these cages leads to the characteristic lanthanide luminescence at both the visible and the near-infrared regions, depending on the lanthanide ions used. Through the assembly-disassembly process, luminescent turn-off sensing toward penicillin among several widely used antibiotics has also been demonstrated with the Europium cage, featuring a limit of detection as low as 0.88 ppb (S/N = 3). Our results pave the way for the construction of chiral 4d-4f supramolecular cages which may find potential applications in luminescent sensing and/or labeling reagents.