Short Communication: Radon testing via a state tobacco quitline.

Objective: Exposure to radon gas at home is the second largest cause of lung cancer after smoking and dramatically increases smokers' risk of lung cancer. State tobacco quitlines are uniquely positioned to inform smokers about radon, yet, to our knowledge, none does so. We explored the feasibility of introducing free radon tests via the tobacco quitline in North Dakota, a state with one of the highest radon levels in the U.S. Methods: Five hundred consecutive callers to the ND Quits Tobacco quitline from February 2021 to February 2023 were invited to complete a brief radon questionnaire and receive a free radon test kit. Radon tests were bar-coded so that the return rate of the tests and the radon levels could be determined. Results: Two hundred fifty-one (51 %) callers completed the questionnaire and seventy-five radon tests were successfully returned to the laboratory. More than one third of the test results were ≥ 4.0 pCi/L, the action level recommended by the EPA. Only 1 in 5 participants reported knowing that radon caused lung cancer. Conclusion: Radon knowledge among ND smokers is poor. Radon test distribution via quitlines is feasible and may be a valuable addition to quitline services, particularly in states with high radon levels.

Collaborative Fieldwork Supervision: Its Value and Use in Occupational Therapy.

Collaborative supervision is not new to occupational therapy; however, its use remains limited. To identify factors affecting the perceived value and use of collaborative supervision, a survey was developed and disseminated to fieldwork educators seeking their opinions and experiences. The survey had 382 respondents. Familiarity with constructs and prior experience using this collaborative supervision seem to be the highest predictor of use. Understanding the impact of practitioner attributes on the perceived value of collaborative fieldwork can help expand the use of collaborative fieldwork supervision.

Effect of COVID-19 and its vaccines on surgical and postsurgical mortality, ICU admission and 90-day readmission for elective surgical procedures in a United States veteran population.

BACKGROUND: We investigated how COVID-19 infection and vaccination impact elective surgical outcomes. METHODS: We retrospectively compared pre-pandemic (P) veterans to those with COVID (C) more than three weeks preoperatively or no COVID (NC) history after carotid endarterectomy, CABG, hip replacement, or colectomy. Subgroup analysis considered vaccination. Age and sex propensity matching, and conditional logistic regression analyzed one-year-mortality, 90-day-readmission, and ICU requirements among 519 â€‹C, 1038 NC, and 2076 â€‹P, culled from 61,641 veterans. RESULTS: NC, C, and P had similar ICU requirements and mortality, although NC required fewer readmissions. However, NC immunized at least once were readmitted and died less commonly than C who received at least one immunization. CONCLUSIONS: SARS-CoV-2 history increased readmission without affecting ICU requirement or mortality. Further studies should evaluate whether the worse outcomes in postoperative patients with histories of both COVID infection and one vaccination reflect the effects of incomplete vaccination or dataset limitations.

Comparing Communication Methods to Increase Radon Knowledge and Home Testing: A Randomized Controlled Trial in a High-Radon City.

INTRODUCTION: Exposure to residential radon is a preventable cause of cancer. Prevention requires testing, but the percentage of homes that have been tested is small. One reason for the low testing rates may be that printed brochures fail to motivate people to obtain and return a radon test. METHODS: We developed a radon app for smartphones that contained the same information as printed brochures. We conducted a randomized, controlled trial that compared the app to brochures in a population comprised largely of homeowners. Cognitive endpoints included radon knowledge, attitudes toward testing, perceived severity and susceptibility to radon, and response and self-efficacy. Behavioral endpoints were participants' requests for a free radon test and the return of the test to the lab. Participants (N = 116) were residents of Grand Forks, North Dakota, a city with one of the nation's highest radon levels. Data were analyzed by general linear models and logistic regression. RESULTS: Participants in both conditions showed significant increases in radon knowledge (p < 0.001), perceived susceptibility (p < 0.001), and self-efficacy (p = 0.004). There was a significant interaction, with app users showing greater increases. After controlling for income, app users were three times more likely to request a free radon test. However, contrary to expectation, app users were 70% less likely to return it to the lab (p < 0.01). CONCLUSIONS: Our findings confirm the superiority of smartphones in stimulating radon test requests. We speculate that the advantage of brochures in promoting test returns may be due to their ability to serve as physical reminders.

Interventions to promote home radon testing: A randomized clinical trial of a smartphone app vs. printed brochures.

Radon is a preventable cause of lung cancer, but the percentage of homes tested for radon is low. We previously developed a smartphone app that informs users about radon and allows them to request a free radon test. Here we conducted a randomized, controlled trial comparing the radon app versus printed brochures on radon knowledge, attitudes, and behaviors, including the proportion of participants requesting radon tests. Participants (N = 138) were undergraduates at a midwestern university. Data were analyzed by t-tests, general linear models, and logistic regression. App users showed significantly greater increases in radon knowledge (p = 0.010) and self-efficacy (p < 0.001) and requested tests three times more often than brochure recipients (41.4% vs. 13.2%, p < 0.001). However, the rate of test usage in each condition was low, ~3%. In conclusion, the radon app markedly outperformed brochures in increasing knowledge and requests for radon tests. Future work should focus on methods to increase test usage.

Screening for fetal alcohol spectrum disorder in infants and young children.

Introduction: With an estimated prevalence of up to five percent in the general population, fetal alcohol spectrum disorders (FASD) are the most common neurodevelopmental disorder and more prevalent than autism. Early identification and subsequent early intervention have the potential to improve developmental trajectory of children with FASD. In addition, new research suggests supplementation with choline may ameliorate the developmental impairments associated with prenatal alcohol exposure. Availability of a screening tool with acceptable epidemiologic performance criteria may be clinical useful in identification of young children at increased risk for FASD. In this paper we describe the Early Fetal Alcohol Spectrum Disorder Screening Test (E-FAST) to identify young children at increased risk for an FASD. Methods: We developed the E-FAST dataset from previously published studies, comprised of 281 children under 5 years of age, 180 (64.1%) were diagnosed with FASD and 101 (35.9%) were non-FASD. Analysis: The analysis identified seven useful variables (prenatal alcohol exposure, ADHD (Attention Deficit Hyperactivity Disorder), foster care or adopted, small OFC (occipital frontal circumference), communication impairments, impaired social skills, and cognitive deficits. All variables were categorized as yes/no for ease of use in a screening tool. Risk ratios for each of the seven indicators were estimated using two-way table analyses. Weights for each variable were estimated based on the relative strength of their odds ratios. Results: The average age was 2.7 years of age (S.D. 1.29) and ranged from infant (6.4%) to 4 years old (35.9%). Maternal alcohol use alone had a sensitivity of 0.97, specificity 0.65, and accuracy 0.86. For the combined seven variables, sensitivity was 0.94, specificity 0.74, and accuracy 0.87. Thus, the seven-item E-FAST screen had acceptable epidemiologic screening characteristics. Discussion: In the United States, up to 547 infants with FASD are born each day which far exceeds the capacity of multidisciplinary diagnostic clinics. During routine clinical management of infants and young children the use of an evidence-based screening tool provides a time efficient means to exclude large numbers of young children from further follow-up for FASD. Conversely, a positive screen identifies a smaller number of children at increased risk for FASD requiring more intensive evaluation and follow-up.

Exploring Clinical Risk Factors for Breast Cancer Among American Indian Women.

Objective: Very little is known about the breast cancer risk profile among American Indian women. Previous research shows that the proportion of American Indian/Alaska Native women with baseline characteristics (commonly known breast cancer risk factors) differs from other ethnicities. This retrospective case control study was designed to the explore the association of these factors among American Indian women with and without breast cancer. Methods: Cases and controls were retrospectively selected from the medical records of American Indian women who obtained their health care from Quentin N. Burdick Memorial Health Care Facility (Indian Health Service) in Belcourt, ND. For each woman with breast cancer (n = 141), two controls were selected when possible (n = 278). Risk factors examined included woman's age, age at first live birth, age of menarche, the number of previous benign breast biopsies, the total number of first-degree relatives with breast cancer, body mass index and parity. Odds ratios and 95% confidence intervals were calculated using logistic regression. Results: Many of the associations found among American Indian women who obtained their health care from Quentin N. Burdick Memorial Health Care Facility (Indian Health Service) in Belcourt, ND, between risk factors commonly identified in other populations and breast cancer were weakly positive. Nulliparity was the only risk factor to consistently show a positive significant association (OR = 2.87, 95% CI 1.16-0.7.12). Conclusion: Disparities in breast cancer incidence, mortality and screening among Northern Plains American Indian emphasize the need to better understand the risk factors associated with breast cancer in this population. Based on the results of this study, the value of current risk prediction models in American Indian communities is uncertain and clinicians should be cautious in using these models to inform American Indian patients of their risk for breast cancer.

Day-to-day blood pressure variability predicts poor outcomes following percutaneous coronary intervention: A retrospective study.

BACKGROUND: For patients with cardiovascular disease, blood pressure variability (BPV), distinct from hypertension, is an important determinant of adverse cardiac events. Whether pre-operative BPV adversely affects outcomes after percutaneous coronary intervention (PCI) is to this point unclear. AIM: To investigate the relationship between blood pressure variability and outcomes for patients post-PCI. METHODS: Patients undergoing PCI in a single state in 2017 were studied (n = 647). Systolic and diastolic BPV, defined as both the largest change and standard deviation for the 3-60 mo prior to PCI was calculated and patients with more than ten blood pressure measurements in that time were included for analysis (n = 471). Adverse outcomes were identified up to a year following the procedure, including major adverse cardiac events (MACE), myocardial infarction, cerebrovascular accident, death, and all-cause hospitalization. RESULTS: Visit-to-visit systolic BPV, as measured by both standard deviation and largest change, was higher in patients who had myocardial infarction, were readmitted, or died within one year following PCI. Systolic BPV, as measured by largest change or standard deviation, was higher in patients who had MACE, or readmissions (P < 0.05). Diastolic BPV, as measured by largest change, was higher in patients with MACE and readmissions (P < 0.05). CONCLUSION: As BPV is easily measured and captured in the electronic medical record, these findings describe a novel method of identifying at-risk patients who undergo PCI. Aggressive risk modification for patients with elevated BPV and known coronary artery disease is indicated.

Criterion Validity of Radon Test Values Reported by a Commercial Laboratory versus the Environmental Protection Agency.

Objective: Radon exposure is a proven cause of lung cancer and is a possible cause of other diseases. Recently, several ecologic studies explored the correlation of county-wide incidence rates for non-lung cancers with residential radon levels, using radon data reported by a commercial laboratory. However, the validity of the commercial radon data, i.e., whether they are an accurate representation of the radon levels in the counties from which they were drawn, is unknown. Methods: We compared county-wide radon data from the commercial laboratory with corresponding measurements from the same counties reported previously by the Environmental Protection Agency (EPA). Matching data were available for four states, Iowa, North Dakota, Texas, and Wisconsin, and were compared by paired t-tests. Criterion validity of the commercial tests, i.e., how well the commercial data predicted the EPA data, was tested using non-parametric methods, Kendall's tau, Lin's concordance, and Passing−Bablok regression. Results: The commercial and EPA data pairs from the four states were significantly positively correlated, although the size of the correlations was modest (tau = 0.490, Lin = 0.600). Passing−Bablok regression indicated that the commercial radon values were significantly higher than their EPA pairs and significantly overestimated radon at low levels (<4 pCi/L, p < 0.001). Conclusions: The commercial laboratory data were moderately predictive of EPA radon levels at the county level but were significantly biased upwards at low levels. The disagreement likely has several causes, including selection bias from homes that were tested voluntarily. Ecologic studies that employ radon data obtained from commercial laboratories should be interpreted with caution.

Trends in means and distributional characteristics of cardiorespiratory endurance performance for Italian children (1984-2010).

Cardiorespiratory endurance (CRE) is an important health marker. The aim of this study was to examine temporal trends of CRE performance for Italian children between 1984 and 2010. Using a repeated cross-sectional study design, 5303 CRE test results were available for 2520 children aged 11-13 years from a single Northern Italian middle-high school between 1984 and 2010. CRE was measured as 1000-m and 12-min run test performance. With adjustments for BMI, temporal trends in means were estimated using linear regression, with trends in distributional characteristics described visually and estimated as the ratio of coefficients of variation (CVs). There was a significant small increase in BMI (effect size (ES) [95%CI]: 0.40 [0.32, 0.48]) over the entire period. When adjusted for BMI, there were significant small to moderate declines in mean running speed (ES [95%CI]: 1000-m, - 0.34 [-0.39, - 0.29]); 12-min, - 0.65 [-0.70, - 0.60]). Declines were larger for boys compared to girls. Variability substantially increased over time (ratio of CVs: range, 1.7-2.9), with larger declines in children with low running speed compared to children with average or high running speed. Our findings may be important to public health because low CRE is significantly related to current and future health.

Addressing Puberty Challenges for Adolescents With Autism Spectrum Disorder: A Survey of Occupational Therapy Practice Trends.

IMPORTANCE: Understanding occupational therapy practice patterns for adolescents who have autism spectrum disorder (ASD) provides a baseline to determine areas of need and effective interventions. OBJECTIVE: To identify puberty-related challenges addressed and interventions used by occupational therapy practitioners with adolescents ages 8-16 yr with ASD. DESIGN: A nonexperimental survey design with a stratified random sample was used. SETTING: The Occupational Therapy-Autism and Puberty Survey was distributed in the United States online through the Qualtrics platform (available October 2017-January 2018). PARTICIPANTS: Occupational therapists (89%) or occupational therapy assistants with experience with adolescents who have ASD were included. The 71 eligible respondents were primarily White women with an average 16 yr of experience. Outcomes and Measures: Nine key challenges and 11 interventions regarding puberty and ASD were identified. Hypotheses were generated before data collection. RESULTS: More practitioners (>47%) addressed emotional regulation and personal hygiene, and fewer (<26%) addressed menstruation, safety, and masturbation. Nearly all practitioners (>92%) reported using social learning approaches and behavioral strategies, and most (>80%) reporting having received education in these interventions. Significant differences were found between reported education and use of behavioral skills training incorporating applied behavioral analysis (p < .001), parent training (p = .002), and technology (p = .003). CONCLUSIONS AND RELEVANCE: Practitioners are neglecting to address puberty-specific challenges with adolescents who have ASD. Opportunities exist to expand the interventions used and challenges addressed by occupational therapy practitioners for adolescents with ASD. What This Article Adds: This article expands occupational therapy literature by giving a baseline understanding of the puberty-related challenges that practitioners are addressing with adolescents who have ASD. This information can assist the profession in developing effective interventions and educational opportunities to allow practitioners to successfully address puberty-specific challenges.

Radon Knowledge and Practices Among Family Physicians in a High Radon State.

BACKGROUND: Exposure to radon at home is the largest cause of lung cancer after smoking, and the combination of smoking and radon increases lung cancer risk several-fold. North Dakota has some of the highest residential radon levels in the United States. Although family physicians in North Dakota commonly counsel patients about smoking cessation, little is known about their knowledge and practices concerning radon. METHODS: We mailed a questionnaire to 350 North Dakota family physicians regarding radon knowledge, beliefs, their own radon testing, and radon counseling of patients. The responses were analyzed by descriptive statistics, analysis of variance, and logistic regression. RESULTS: Sixty-one percent of the surveys were completed. Seventy percent of family physicians correctly identified radon as radioactive; 67% reported that they do not inform patients about radon; and 80% reported never discussing the combined hazards of radon and smoking. Conversely, 35% of family physicians reported that they tested their own homes for radon. DISCUSSION: Most North Dakota family physicians are knowledgeable about radon, and more than one third have tested their own homes. However, only a minority transmit this knowledge to their patients. Future efforts should educate physicians about communicating radon risks, especially in conjunction with smoking.

Preoperative and Intraoperative Blood Pressure Variability Independently Correlate with Outcomes.

BACKGROUND: Blood pressure variability (BPV) describes visit-to-visit blood pressure (BP) changes independent of hypertension. Preoperative BPV and intraoperative BPV are associated with increased postoperative outcomes. We investigated the impact of both preoperative BPV and intraoperative BPV on elective surgical outcomes, specifically whether preoperative BPV and intraoperative BPV were independent risk factors for surgical complications. MATERIALS AND METHODS: We investigated 600 patients undergoing elective surgery lasting more than two h and who had ≥8 outpatient BP recordings over three preoperative years. Age, sex, ethnicity, BMI, current medical problems, and medications at time of surgery were recorded. BPV was calculated as the standard deviation (SD) of systolic or diastolic BP for the 369 valid patients. Average BPV were compared between adverse outcomes of readmission, wound infection, acute kidney injury, death, myocardial infarction, and cerebral vascular accident. RESULTS: Three-hundred-sixty-nine (52.6% male, 47.4% female, 98.1% non-Hispanic) patients (mean age 62.5) were included in the study. Preoperative systolic (P = 0.043) and diastolic (P = 0.009) BPV were higher for patients with the combined endpoint of all adverse events. Preoperative systolic BPV was correlated with intraoperative BPV (P = 0.010). Both systolic and diastolic preoperative BPV was found to be independent from intraoperative BPV. Otolaryngology procedures were associated with less adverse outcomes (P = 0.034), whil antimicrobials (P = 0.022), autonomic drugs (P < 0.001), or respiratory drugs (P = 0.032) was associated with an increased likelihood of adverse outcome. CONCLUSION: Preoperative DBPV is associated with increased risk of readmission, wound infection and the combined endpoint of all adverse events. Intraoperative systolic blood pressure variability (SPBV) is associated with increased risk of acute kidney injury and the combined endpoint of all adverse events. Preoperative DBPV and intraoperative SBPV are independent risk factors for ninety-d postoperative outcomes. BPV should be considered in individualized risk assessment when assessing patient eligibility for elective procedures.

Correlations Among Visit-to-Visit Blood Pressure Variability and Treatment With Antihypertensive Medication With Long-Term Adverse Outcomes in a Large Veteran Cohort.

BACKGROUND: Blood pressure variability (BPV) is associated with adverse events (AEs) independently of hypertension. It has been suggested that calcium channel blockers (CCBs) may reduce BPV, and thus be particularly valuable in hypertensives with high BPV. We sought to investigate how CCB affect BPV progression and whether long-term adverse effects of BPV differ after CCB treatment than after treatment with other antihypertensives. METHODS: We retrospectively analyzed 25,268 US veterans who had been followed for 3 years without hypertensive therapy, started on a single class of antihypertensive agents (thiazides, CCBs, ACE inhibitors, or beta blockers [BBs]), treated for 6 years, and then followed for 3 additional years. BPV was calculated as SD of systolic or diastolic blood pressures from at least 10 measurements over each 3-year period. A combined AE endpoint included hospitalization, coronary artery bypass grafting, carotid endarterectomy, angioplasty, amputation, arteriovenous fistula creation, and mortality was assessed in years 9-12. RESULTS: Post-medication high BPV and BB or thiazide use were associated with increased AE risk. Medication type also affected mean post-medication BPV. The effects of medications except for BBs on AE and mortality was independent of the patient BPV. CONCLUSIONS: The possible deleterious effects of thiazides should be considered within the context of the study population, who were mostly male and received only a single class of hypertensives. While CCB may ameliorate BPV over time, this study does not support choosing CCB over other agents specifically to lessen BPV-associated risk.

Brain cancer incidence rates and the presence of nuclear reactors in US states: a hypothesis-generating study.

BACKGROUND: The etiology of brain cancer is poorly understood. The only confirmed environmental risk factor is exposure to ionizing radiation. Because nuclear reactors emit ionizing radiation, we examined brain cancer incidence rates in the USA in relation to the presence of nuclear reactors per state. METHODS: Data on brain cancer incidence rates per state for Whites by sex for three age groups (all ages, 50 and older, and under 50) were obtained from cancer registries. The location, number, and type of nuclear reactor, i.e., power or research reactor, was obtained from public sources. We examined the association between these variables using multivariate linear regression and ANOVA. RESULTS: Brain cancer incidence rates were not associated with the number of nuclear power reactors. Conversely, incidence rates per state increased with the number of nuclear research reactors. This was significant for both sexes combined and for males in the 'all ages' category (ß = 0.08, p = 0.0319 and ß = 0.12, p = 0.0277, respectively), and for both sexes combined in the'50 and older' category (ß = 0.18, p = 0.0163). Brain cancer incidence rates for counties with research reactors were significantly higher than the corresponding rates for their states overall (p = 0.0140). These findings were not explicable by known confounders. CONCLUSIONS: Brain cancer incidence rates are positively associated with the number of nuclear research reactors per state. These findings merit further exploration and suggest new opportunities for research in brain cancer epidemiology.

A Validation Study of the Alcohol Related Neurodevelopmental Disorders Behavioral Checklist.

BACKGROUND: The initial confirmatory factor analysis of the Alcohol Related Neurodevelopmental Disorder Behavioral Checklist (ABC) utilized a population of 203 children. The analysis identified 10 independent measures (executive functioning, attention and concentration, cognition, memory, confabulation, gullibility, communication skills, academic skills, living/social skills, and juvenile justice). The 10 measures differentiated children with FASD from non-FASD controls. In this study, we present a validity study of the ABC using a different population of children with FASD and non-FASD controls. METHODS: A chart review identified 224 children with ABC checklist scores who had been evaluated for FASD. From this sample, we implemented a case-control study of 76 children diagnosed with FASD and 76 non-FASD controls who were matched by gender and closest age in years (mean age was 8.5 years). RESULTS: The averages of the total score and individual domain scores were compared between the 2 data sets and then between children with FASD and non-FASD controls. Children with FASD had significantly higher scores on all 10 measures than the non-FASD controls. There were very high sensitivity and specificity scores for the total score cutoff and for all 10 of the individual measures. CONCLUSIONS: In an independent sample, we found minimal differences between the previous data and the current validation study on measures of average total score cutoffs, scores for the 10 measures and correlations. Combining the 2 samples yielded robust differences in scores between children with FASD and non-FASD controls. The sensitivity, specificity and accuracy estimates were also very high. The ABC Screen appears to have acceptable epidemiologic performance data to support its use as a screening tool and as an initial step in differentiating children with FASD from those who do not have FASD.

Protective factors against tobacco and alcohol use among pregnant women from a tribal nation in the Central United States.

Identifying social determinants of tobacco and alcohol use during pregnancy is critical to improving health outcomes for the next generation. This is especially important on a rural Tribal Nation where influences such as isolation, cultural barriers, and historical trauma have made it uniquely challenging to prevent substance use during pregnancy. The purpose of this study is to identify population-specific factors that are protective against smoking and drinking during pregnancy. We used data from 421 pregnancies collected as a part of the Safe Passages study from a rural Tribal Nation in the central United States. Pregnant women were classified as women who did not smoke (n = 84), women who quit during pregnancy (n = 23), women who smoked during pregnancy (n = 314), and women who both smoked and drank alcohol during pregnancy (n = 149). Demographic data revealed that 28.8% of the mothers were currently employed, and 91.8% of mothers reported a household income of less than $3,000 per year. Substance use rates were higher than national averages: 74.6% smoked during pregnancy and 35.4% of the women both smoked and drank alcohol during pregnancy. Five factors were identified as being protective against substance use during pregnancy: 1) living with someone (81% less likely to smoke and 92% less likely to smoke and drink), 2) having at least 12 years of education (128% less likely to smoke, and 126% less likely to smoke and drink), 3) having over 12 years of education (235% less likely to smoke, and 206% less likely to smoke and drink), 4) being employed (158% less likely to smoke, and 111% less likely to smoke and drink), and 5) not being depressed (214% less likely to smoke, and 229% less likely to smoke and drink). These social determinants should be considered for intervention research to decrease rates of substance use during pregnancy.

Women who develop ovarian cancer show an increase in serum calcium and a decrease in serum albumin. A longitudinal study in the Janus Serum Bank Cohort.

BACKGROUND: Ovarian cancer is associated with high serum calcium and low serum albumin in clinical and epidemiologic studies. Whether high calcium and low albumin predispose to ovarian cancer or reflect existing cancer is unclear. OBJECTIVE: Test the hypothesis that serum calcium increases and serum albumin decreases in women who develop ovarian cancer. METHODS: Two hundred and four women donated sera to the Janus Serum Bank in Norway pre- and post-diagnosis of ovarian cancer, donations separated by approximately 14 years. We measured calcium and albumin in these sera and calculated the albumin-corrected calcium. Sera were adjusted for patient age and storage time. RESULTS: Post-diagnosis, mean age- and storage-adjusted calcium increased, from 2.53 to 2.68 mmol/L (p < .001). Mean age- and storage-adjusted, albumin-corrected calcium increased from 2.3 to 2.7 mmol/L (p < .001). Conversely, mean age- and storage-adjusted albumin decreased, from a mean of 51.3 to 40.9 g/L (p < .001). Significant changes were observed in women with early stage and metastatic cancer. CONCLUSIONS: These data support the hypothesis that calcium and albumin are serum biomarkers of extant ovarian cancer. Longitudinal changes in calcium and albumin may be useful in ovarian cancer early detection.

IGF-1R Inhibitor Ameliorates Neuroinflammation in an Alzheimer's Disease Transgenic Mouse Model.

Aging is a major risk factor for Alzheimer's disease (AD). Insulin-like growth factor-1 receptor (IGF-1R) regulates general aging and lifespan. However, the contribution of IGF-1 to age-related AD pathology and progression is highly controversial. Based on our previous work, AßPP/PS1 double transgenic mice, which express human mutant amyloid precursor protein (APP) and presenilin-1 (PS-1), demonstrated a decrease in brain IGF-1 levels when they were crossed with IGF-1 deficient Ames dwarf mice (df/df). Subsequently, a reduction in gliosis, amyloid-ß (Aß) plaque deposition, and Aß1-40/42 concentrations were observed in this mouse model. This supported the hypothesis that IGF-1 may contribute to the progression of the disease. To assess the role of IGF-1 in AD, 9-10-month-old male littermate control wild type and AßPP/PS1 mice were randomly divided into two treatment groups including control vehicle (DMSO) and picropodophyllin (PPP), a selective, competitive, and reversible IGF-1R inhibitor. The brain penetrant inhibitor was given ip. at 1 mg/kg/day. Mice were sacrificed after 7 days of daily injection and the brains, spleens, and livers were collected to quantify histologic and biochemical changes. The PPP-treated AßPP/PS1 mice demonstrated attenuated insoluble Aß1-40/42. Additionally, an attenuation in microgliosis and protein p-tyrosine levels was observed due to drug treatment in the hippocampus. Our data suggest IGF-1R signaling is associated with disease progression in this mouse model. More importantly, modulation of the brain IGF-1R signaling pathway, even at mid-life, was enough to attenuate aspects of the disease phenotype. This suggests that small molecule therapy targeting the IGF-1R pathway may be viable for late-stage disease treatment.

Probiotics ameliorate intestinal pathophysiology in a mouse model of Alzheimer's disease.

Evidence suggests that changes in intestinal microbiota may affect the central nervous system. However, it is unclear whether alteration of intestinal microbiota affects progression of Alzheimer's disease (AD). To understand this, wild-type control (C57BL/6) mice were compared with the AppNL-G-F model of disease. We used probiotic supplementation to manipulate the gut microbiota. Fecal samples were collected for microbiota profiling. To study brain and intestinal inflammation, biochemical and histological analyses were performed. Altered metabolic pathways were examined by quantifying eicosanoid and bile acid profiles in the brain and serum using ultraperformance liquid chromatography-tandem mass spectrometry. We observed that brain pathology was associated with intestinal dysbiosis and increased intestinal inflammation and leakiness in AppNL-G-F mice. Probiotic supplementation significantly decreased intestinal inflammation and gut permeability with minimal effect on amyloid-ß, cytokine, or gliosis levels in the brain. Concentrations of several bile acids and prostaglandins were altered in the serum and brain because of AD or probiotic supplementation. Our study characterizes intestinal dysfunction in an AD mouse model and the potential of probiotic intervention to ameliorate this condition.