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As a component of robust designation field, the IPA technique is reputed for providing a quantified index of expectation value from multiple patients' biological index series. The expectation value can be a specific drug in blood concentration reading, or the potential risk of a patient with a clinical syndrome, or the optimal trigger timing for CTA. This study verified the inverse problem algorithm (IPA) by integrated case studies in preventive medicine. The risk factors can be Age, BSA (body surface area), Sugar AC, MAP (mean artery pressure), or others. The risk factor index is normalized to eliminate the physical dimensionality and yield a quantified index between -1.0 and +1.0, whereas the middle point, 0.0, implies the average risk factor index. The quantified indices of patients are organized into a vast data matrix for deriving the inverse matrix and obtaining the column matrix of the compromised solution. This study preset the STATISTICA program to derive the solution according to default quasi-Newton or Rosenbrock analysis. The derived solution can be defined as a nonlinear semi-empirical formula with multiple terms to express the specific expectation value. Accordingly, six IPA-related papers are comprehensively integrated to explore the applicability and critical points in adopting the IPA technique for preventive medicine tasks. Besides, the interpretation of cross-interactions among risk factors to affect the performing of IPA computation and the convergence rate of a semi-empirical formula related to the final constant term are also analyzed and discussed in detail. The integrated IPA technique is instrumental in exploring potential syndromes in preventive medicine. [ABSTRACT FROM AUTHOR]

Summary Dysregulated lipid metabolism is a characteristic of malignancies. Sterol regulatory element binding protein 1 (SREBP-1), a transcription factor playing a central role in lipid metabolism, is highly activated in malignancies. Here, we unraveled a link between miR-29 and the SCAP (SREBP cleavage-activating protein)/SREBP-1 pathway in glioblastoma (GBM) growth. Epidermal growth factor receptor (EGFR) signaling enhances miR-29 expression in GBM cells via upregulation of SCAP/SREBP-1, and SREBP-1 activates miR-29 expression via binding to specific sites in its promoter. In turn, miR-29 inhibits SCAP and SREBP-1 expression by interacting with their 3′ UTRs. miR-29 transfection suppressed lipid synthesis and GBM cell growth, which were rescued by the addition of fatty acids or N-terminal SREBP-1 expression. Xenograft studies showed that miR-29 mimics significantly inhibit GBM growth and prolong the survival of GBM-bearing mice. Our study reveals a previously unrecognized negative feedback loop in SCAP/SREBP-1 signaling mediated by miR-29 and suggests that miR-29 treatment may represent an effective means to target GBM. [ABSTRACT FROM AUTHOR]

Summary Tumorigenesis is associated with increased glucose consumption and lipogenesis, but how these pathways are interlinked is unclear. Here, we delineate a pathway in which EGFR signaling, by increasing glucose uptake, promotes N-glycosylation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and consequent activation of SREBP-1, an ER-bound transcription factor with central roles in lipid metabolism. Glycosylation stabilizes SCAP and reduces its association with Insig-1, allowing movement of SCAP/SREBP to the Golgi and consequent proteolytic activation of SREBP. Xenograft studies reveal that blocking SCAP N-glycosylation ameliorates EGFRvIII-driven glioblastoma growth. Thus, SCAP acts as key glucose-responsive protein linking oncogenic signaling and fuel availability to SREBP-dependent lipogenesis. Targeting SCAP N-glycosylation may provide a promising means of treating malignancies and metabolic diseases. [ABSTRACT FROM AUTHOR]

Local acceptance of wind energy technology has become an important factor to consider when designing local and national wind energy technological innovation policies. Previous studies have investigated the factors that shape the local acceptance of wind power in high-income countries. However, to the best of our knowledge, these factors had not been investigated in China. Utilizing a survey and quantitative analysis, we have identified the factors that are correlated with local acceptance of wind power in China. We conducted our study in the city of Jiuquan, Gansu Province, which currently possesses the largest installed capacity for wind power generation in China. Two factors, namely, perceived economic benefits and perceived environmental costs, influence local acceptance of wind power in China most significantly. Local acceptance of wind power in China can be described as “not in my backyard, but not far away from me”. In other words, the acceptance rate is lowest when the source of wind power is located in their village or community, highest when the project is located in their county and city and decreases for projects that are constructed further away. [ABSTRACT FROM AUTHOR]

Introduction: Low body weight in Parkinson's disease (PD) is poorly understood despite the associated risks of malnutrition, fractures, and death. Sarcopenia (loss of muscle bulk and strength) and frailty are geriatric syndromes that are likewise associated with adverse health outcomes, yet have received scant attention in PD. We studied body composition, sarcopenia, frailty, and their clinico-biological correlates in PD.Methods: 93 patients and 78 spousal/sibling controls underwent comprehensive assessment of diet, clinical status, muscle strength/performance, frailty, body composition (using dual-energy X-ray absorptiometry), and serum levels of neurogastrointestinal hormones and inflammatory markers.Results: PD patients were older than controls (66.0 ± 8.5 vs. 62.4 ± 8.4years, P = 0.003). Mean body mass index (24.0 ± 0.4 vs. 25.6 ± 0.5kg/m2, Padjusted = 0.016), fat mass index (7.4 ± 0.3 vs. 9.0 ± 0.3kg/m2, Padjusted<0.001), and whole-body fat percentage (30.7 ± 0.8 vs. 35.7 ± 0.9%, Padjusted<0.001) were lower in patients, even after controlling for age and gender. There were no between-group differences in skeletal muscle mass index and whole-body bone mineral density. Body composition parameters did not correlate with disease duration or motor severity. Reduced whole-body fat percentage was associated with higher risk of motor response complications as well as higher levels of insulin-growth factor-1 and inflammatory markers. PD patients had a higher prevalence of sarcopenia (17.2% vs. 10.3%, Padjusted = 0.340) and frailty (69.4% vs. 24.2%, Padjusted = 0.010). Older age and worse PD motor severity were predictors of frailty in PD.Conclusions: We found reduced body fat with relatively preserved skeletal muscle mass, and a high prevalence of frailty, in PD. Further studies are needed to understand the patho-mechanisms underlying these alterations. [ABSTRACT FROM AUTHOR]

We have previously shown that givinostat can induce potent apoptosis in the BCR-ABL1 -positive, TP53 -wild type B-cell acute lymphoblastic leukemia (B-ALL) cell line SUP-B15. We extend our studies here to two additional B-ALL cell lines, BCR-ABL1 -negative CCRF-SB and p210 BCR-ABL1 -positive NAML1. Givinostat induced significant cell growth inhibition in both cell lines, with an IC50 of 0.65 ± 0.052 μM and 0.25 ± 0.028 μM in CCRF-SB and NAML1, respectively. The key signal protein of the BCR-ABL1, Crk-L1, was significantly reduced by givinostat treatment in NAML1. As in SUP-B15, givinostat induced apoptosis in both cell lines but showed different levels of cleavage of the procaspase proteins Casp-3, Casp-7 and PARP. Levels of cell cycle-DNA repair regulator p21, CHK1 and FANCD2 levels were markedly affected by givinostat treatment. These data further enrich our understanding of the mechanisms of the antineoplastic effects of givinostat in B-ALL and provide a preclinical rationale for the inclusion of givinostat or similar agent in leukemia therapy. [ABSTRACT FROM AUTHOR]