Predictors of behavioral cancer risk factors and preventive behaviors among Nebraskans

BackgroundThe overall incidence rate of cancer in Nebraska is higher than the national average with cancer being the second leading cause of death in the state. Interventions are required to reduce the cancer burden; however, further research is first needed to identify behavioral cancer risk factors and preventive behaviors among Nebraskans that can be targeted.MethodsA statewide cross-sectional survey of Nebraskans aged 19 and older was conducted in 2019 using an address-based sampling method (n = 1640). Multivariable logistic regression was used to examine factors associated with being up-to-date on cancer screening and with behavioral cancer risk factors and preventive behaviors.Results93.42% of Nebraskans did not meet the daily recommended consumption of fruits and vegetables, and 71.51% did not meet weekly physical activity guidelines. The proportion of adults up to date on cancer screening was 64.57% for breast, 68.83% for cervical, 69.01% for colorectal, and 24.07% for skin cancers. Individuals 65–74 (OR: 3.40, 95% CI: 1.52–7.62) and 75 or older (OR: 3.30, 95% CI: 1.35–8.07) were more likely to be current with their colorectal cancer screening compared to ages 50–64. Hispanics were less likely to be current with mammograms (OR: 0.06, 95% CI: 0.01–0.71) and ever screened for cervical cancer (OR:0.13, 95% CI: 0.02–0.94) compared to Non-Hispanic Whites.ConclusionsDisparities in cancer screening and risk and preventive behaviors exist in Nebraska.ImpactThe study highlights a need for continuing efforts to improve preventive cancer behaviors for the entire population as well as some high-risk populations in Nebraska.     

Proof-of-Concept Study of Using Supervised Machine Learning Algorithms to Predict Self-Care and Glycemic Control in Type 1 Diabetes Patients on Insulin Pump Therapy

ObjectiveUsing supervised machine learning algorithms (SMLAs), we built models to predict the probability of type 1 diabetes mellitus patients on insulin pump therapy for meeting insulin pump self-management behavioral (IPSMB) criteria and achieving good glycemic response within 6 months.MethodsThis was a single-center retrospective chart review of 100 adult type 1 diabetes mellitus patients on insulin pump therapy (≥6 months). Three SMLAs were deployed: multivariable logistic regression (LR), random forest (RF), and K-nearest neighbor (k-NN); validated using repeated three-fold cross-validation. Performance metrics included area under the curve-Receiver of characteristics for discrimination and Brier scores for calibration.ResultsVariables predictive of adherence with IPSMB criteria were baseline hemoglobin A1c, continuous glucose monitoring, and sex. The models had comparable discriminatory power (LR = 0.74; RF = 0.74; k-NN = 0.72), with the RF model showing better calibration (Brier = 0.151). Predictors of the good glycemic response included baseline hemoglobin A1c, entering carbohydrates, and following the recommended bolus dose, with models comparable in discriminatory power (LR = 0.81, RF = 0.80, k-NN = 0.78) but the RF model being better calibrated (Brier = 0.099).ConclusionThese proof-of-concept analyses demonstrate the feasibility of using SMLAs to develop clinically relevant predictive models of adherence with IPSMB criteria and glycemic control within 6 months. Subject to further study, nonlinear prediction models may perform better.     

A Guide to Generating and Using hiPSC Derived NPCs for the Study of Neurological Diseases

Post-mortem studies of neurological diseases are not ideal for identifying the underlying causes of disease initiation, as many diseases include a long period of disease progression prior to the onset of symptoms. Because fibroblasts from patients and healthy controls can be efficiently reprogrammed into human induced pluripotent stem cells (hiPSCs), and subsequently differentiated into neural progenitor cells (NPCs) and neurons for the study of these diseases, it is now possible to recapitulate the developmental events that occurred prior to symptom onset in patients. We present a method by which to efficiently differentiate hiPSCs into NPCs, which in addition to being capable of further differentiation into functional neurons, can also be robustly passaged, freeze-thawed or transitioned to grow as neurospheres, enabling rapid genetic screening to identify the molecular factors that impact cellular phenotypes including replication, migration, oxidative stress and/or apoptosis. Patient derived hiPSC NPCs are a unique platform, ideally suited for the empirical testing of the cellular or molecular consequences of manipulating gene expression.     

Spatial distribution and historical deposition behaviors of perfluoroalkyl substances (PFASs) in sediments of Lake Chaohu,a shallow eutrophic lake in Eastern China

Sediment samples were collected from the Chaohu Lake basin to investigate the spatial distribution and historical deposition behaviors of 17 perfluoroalkyl substances (PFASs). Concentrations of the total PFASs (∑PFASs) in limnetic sediments ranged from 0.719 to 2.429 ng/g dry weight (dw), with an average of 1.449 ng/g dw. A clear gradient in the spatial distribution was observed from west to east in surface sediments of Lake Chaohu. Perfluorooctane sulfonic acid and perfluorooctanoic acid were predominant in limnetic sediments, with an average of 0.383 and 0.275 ng/g dw, respectively. The ∑PFASs concentrations in riverine sediments were the highest in the Shiwuli River, followed by the Nanfei River. PFASs in riverine sediments indicated that industrial discharge and urban runoff played key roles in PFAS distribution and pollution levels. In vertical profiles, concentrations of the ∑PFASs and PFAS congeners in three sediment cores generally increased with decreasing depths, indicating that the input history of the ∑PFASs could be attributed to the development of industrialization and urbanization in the Chaohu Lake basin. The correlations between PFASs and sedimentary characteristics, organic carbon, nutrients and inorganic salts suggested that both hydrophobic and electrostatic effects played important roles in PFAS distribution and pollution levels in sediments of Lake Chaohu.     

Optogenetic fUSI for brain-wide mapping of neural activity mediating collicular-dependent behaviors

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基于社区生活圈尺度的城市绿色基础设施空间分布与居民就医行为关系研究—以福州市中心城区为例

本研究根据对研究案例区常住居民空间行为轨迹的刻画,就社区生活圈内公园绿地、绿化水平、文化设施、体育健身设施和医疗卫生设施的空间分布与常住居民就医频次的关系进行了分析。发现评价单元内公园绿地面积和绿化水平与居民就医频次具有比较明显的负相关,而文化体育设施与居民就医频次的相关性不明显。在此基础上,进一步分析评价单元内医疗卫生设施的影响,发现其数量、可达性的提高在一定程度上提升了居民就医的频次。故此,便利易得的医疗卫生服务可能增加居民的就医频次,而城市中公园绿地的建设则对于降低居民就医频次有一定的显著作用。相较于增加集中的公园绿地面积,整体性的提高绿化水平则更有益于居民就医频次的降低。     

Psychopathology in 7‐year‐old children with familial high risk of developing schizophrenia spectrum psychosis or bipolar disorder – The Danish High Risk and Resilience Study ‐ VIA 7, a population‐based cohort study

This study aimed to compare the psychopathological profiles of children at familial high risk of schizophrenia spectrum psychosis (FHR‐SZ) or bipolar disorder (FHR‐BP) with population‐based controls. We used Danish nationwide registers to retrieve a cohort of 522 seven‐year‐old children of parents with schizophrenia spectrum psychosis (N=202), bipolar disorder (N=120) or none of these disorders (N=200). Psychopathology was assessed by reports from multiple informants, including children, parents and teachers. Lifetime DSM‐IV diagnoses were ascertained by blinded raters through the Schedule for Affective Disorders and Schizophrenia for School‐Age Children. The dimensional assessment of psychopathology was performed by the Child Behavior Checklist, the Teacher's Report Form, a modified version of the ADHD‐Rating Scale, the Test Observation Form, and the State‐Trait Anxiety Inventory for Children. Current level of functioning was evaluated using the Children's Global Assessment Scale (CGAS). The prevalence of lifetime psychiatric diagnoses was significantly higher in both FHR‐SZ children (38.7%, odds ratio, OR=3.5, 95% confidence interval, CI: 2.2‐5.7, p < 0.001) and FHR‐BP children (35.6%, OR=3.1, 95% CI: 1.8‐5.3, p < 0.001) compared with controls (15.2%). FHR‐SZ children displayed significantly more dimensional psychopathology on all scales and subscales compared with controls except for the Anxious subscale of the Test Observation Form. FHR‐BP children showed higher levels of dimensional psychopathology on several scales and subscales compared with controls, but lower levels compared with FHR‐SZ children. Level of functioning was lower in both FHR‐SZ children (CGAS mean score = 68.2; 95% CI: 66.3‐70.2, p < 0.0001) and FHR‐BP children (73.7; 95% CI: 71.2‐76.3, p < 0.05) compared with controls (77.9; 95% CI: 75.9‐79.9). In conclusion, already at the age of seven, FHR‐SZ and FHR‐BP children show a higher prevalence of a broad spectrum of categorical and dimensional psychopathology compared with controls. These results emphasize the need for developing early intervention strategies towards this vulnerable group of children.     

Ca2+‐Dependent Hyperpolarization Pathways in Sleep Homeostasis and Mental Disorders

Although we are beginning to understand the neuronal and biochemical nature of sleep regulation, questions remain about how sleep is homeostatically regulated. Beyond its importance in basic physiology, understanding sleep may also shed light on psychiatric and neurodevelopmental disorders. Recent genetic studies in mammals revealed several non‐secretory proteins that determine sleep duration. Interestingly, genes identified in these studies are closely related to psychiatric and neurodevelopmental disorders, suggesting that the sleep‐wake cycle shares some common mechanisms with these disorders. Here we review recent sleep studies, including reverse and forward genetic studies, from the perspectives of sleep duration and homeostasis. We then introduce a recent hypothesis for mammalian sleep in which the fast and slow Ca²⁺‐dependent hyperpolarization pathways are pivotal in generating the SWS firing pattern and regulating sleep homeostasis, respectively. Finally, we propose that these intracellular pathways are potential therapeutic targets for achieving depolarization/hyperpolarization (D/H) balance in psychiatric and neurodevelopmental disorders.     

Rescue of CAMDI deletion‐induced delayed radial migration and psychiatric behaviors by HDAC6 inhibitor

The DISC1‐interacting protein CAMDI has been suggested to promote radial migration through centrosome regulation. However, its physiological relevance is unclear. Here, we report the generation and characterization of CAMDI‐deficient mice. CAMDI‐deficient mice exhibit delayed radial migration with aberrant neural circuit formation and psychiatric behaviors including hyperactivity, repetitive behavior, and social abnormality typically observed in autism spectrum disorder patients. Analyses of direct targets of CAMDI identify HDAC6 whose α‐tubulin deacetylase activity is inhibited by CAMDI at the centrosome. CAMDI deficiency increases HDAC6 activity, leading to unstable centrosomes with reduced γ‐tubulin and acetylated α‐tubulin levels. Most importantly, psychiatric behaviors as well as delayed migration are significantly rescued by treatment with Tubastatin A, a specific inhibitor of HDAC6. Our findings indicate that HDAC6 hyperactivation by CAMDI deletion causes psychiatric behaviors, at least in part, through delayed radial migration due to impaired centrosomes.