Explore the vast range of titles available.

\"Preparing to depart Paradise Island forever, Queen Hippolyta learns an untold tale of the legendary Amazon--the return of Atomia! Then Wonder Woman is transported to the 63rd century to save the Amazons from a race of pig-men who have inhabited their island, and from their abandonment of Aphrodite's ways.-- Provided by publisher.

Artificial pancreas system (APS) is a viable option to treat diabetic patients. Researchers, however, have not conclusively determined the best control method for APS. Due to intra-/inter-variability of insulin absorption and action, an individualized algorithm is required to control blood glucose level (BGL) for each patient. To this end, we developed model predictive control (MPC) based on artificial neural networks (ANNs), which combines ANN for BGL prediction based on inputs and MPC for BGL control based on the ANN (NN-MPC). First, we developed a mathematical model for diabetic rats, which was used to identify individual virtual subjects by fitting to empirical data collected through an APS, including BGL data, insulin injection, and food intake. Then, the virtual subjects were used to generate datasets for training ANNs. The NN-MPC determines control actions (insulin injection) based on BGL predicted by the ANN. To evaluate the NN-MPC, we conducted experiments using four virtual subjects under three different scenarios. Overall, the NN-MPC maintained BGL within the normal range about 90% of the time with a mean absolute deviation of 4.7 mg/dl from a desired BGL. Our findings suggest that the NN-MPC can provide subject-specific BGL control in conjunction with a closed-loop APS.

The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development. A spatially resolved transcriptional atlas of the mid-gestational developing human brain has been created using laser-capture microdissection and microarray technology, providing a comprehensive reference resource which also enables new hypotheses about the nature of human brain evolution and the origins of neurodevelopmental disorders. New whole-brain mapping resources With President Barack Obama's BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative now entering year two, this issue of Nature presents two landmark papers that mobilize 'big science' resources to the cause. Hongkui Zeng and colleagues present the first brain-wide, mesoscale connectome for a mammalian species — the laboratory mouse — based on cell-type-specific tracing of axonal projections. The wiring diagram of a complete nervous system has long been available for a small roundworm, but neuronal connectivity data for larger animals has been patchy until now. The new three-dimensional Allen Mouse Brain Connectivity Atlas is a whole-brain connectivity matrix that will provide insights into how brain regions communicate. Much of the data generated in this project will be of relevance to investigations of neural networks in humans and should help to further our understanding of human brain connectivity and its involvement in brain disorders. In a separate report Ed Lein and colleagues present a transcriptional atlas of the mid-gestational human brain at high spatial resolution, based on laser microdissection and DNA microarray technology. The structure and function of the human brain is largely determined by prenatal transcriptional processes that initiate gene expression, but our understanding of the developing brain has been limited. The new data set reveals transcriptional signatures for developmental processes associated with the massive expansion of neocortex during human evolution, and suggests new cortical germinal zones or postmitotic neurons as sites of dynamic expression for many genes associated with neurological or psychiatric disorders.

Type 2 diabetes mellitus (T2DM) is a chronic disease that requires management of blood glucose. According to previous studies, the Dario Digital Diabetes Solution (DDS) is a nonprescription digital health intervention with a smartphone app that has been shown to improve blood glucose control in adults with T2DM. This study aims to investigate the effects of DDS on health care resource use (HCRU) rates, charges, and estimated costs for adults with T2DM. In this retrospective cohort study, patient-level claims data of adults with T2DM were obtained from the Symphony Health Integrated Dataverse, a database containing both inpatient and outpatient claims, including diagnoses and procedures. Using exact and propensity score matching, DDS users and nonusers were matched in a 1:3 ratio. For the primary outcome measure (all-cause HCRU rates, defined as inpatient hospitalization and emergency room visits) and secondary outcome measures (all-cause outpatient visit rates, all-cause HCRU charges, and diabetes mellitus-related HCRU rates and charges), baseline, follow-up, and changes in values were summarized using descriptive statistics, and a multivariable generalized linear model or a 2-part model (including a generalized linear model) was applied. Additional exploratory outcome measures were analyzed. In a sensitivity analysis, a cost-to-charge ratio was calculated and applied to medical claims to estimate medical costs. Following matching, cohorts consisted of 2445 DDS users and 7334 nonusers with similar demographic and baseline characteristics. The all-cause HCRU event rate was 9.3% lower in DDS users compared with nonusers at the 12-month follow-up from the index date. The mean number of events was estimated to be significantly lower in DDS users (0.48 per patient per year [PPPY]; 95% CI 0.44-0.52) than nonusers (0.52 PPPY; 95% CI 0.50-0.55), resulting in an incidence rate ratio of 0.91 (P=.04). Inpatient hospitalization was 23.5% lower in the DDS user cohort compared with the nonuser cohort, with emergency room visit and outpatient visit rates being similar across both cohorts. DDS users were numerically less likely to incur all-cause HCRU charges than nonusers (odds ratio 0.91, 95% CI 0.82-1.01; P=.07). All-cause HCRU charges were 26% lower for DDS users than for nonusers (US $ 12,552 PPPY savings; P<.001). When applying the cost-charge-ratio to the charges, the total estimated cost saving for DDS users was US $5077, of which US $4513 PPPY was attributed to all-cause HCRU and US $564 to all-cause office visits. In this retrospective cohort study of adults in the United States with T2DM, DDS users were found to have lower all-cause HCRU rates than nonusers, driven by significantly lower inpatient hospitalization rates (P<.001). All-cause HCRU charges and estimated costs were shown to be lower for DDS users compared with nonusers.

PurposeThe purpose of this paper is to ascertain the significant stimulating measures/enablers relating to the existing building regulations for promoting the adoption and overcoming the barriers to the uptake and implementation of the green building concept (GBC) in developing countries using Ghana as a case.Design/methodology/approachThe quantitative research approach was used to attain the study’s goal. Purposive and snowball sampling techniques were found to be suitable for collecting data from 292 relevant stakeholders in Ghana’s construction industry. The mean score ranking technique, in conjunction with the relative importance index, was used to establish the relative ranking of, among other things, the stimulus measures for increasing green building uptake in Ghana. An exploratory factor analysis was also used to classify the most significant stimulation strategies for improving green building uptake.Findings“Educational programmes relevant to GBTs for developers, contractors, and policymakers,” “sufficient information on the cost and benefits of GBTs” and “mandated green building codes and regulations” were the top three listed stimulating measures to promote increasing use of green building technologies (GBTs). The enablers were classified as follows: government regulations and policies; commitment and GB research; education and publicity; and incentives and support.Research limitations/implicationsThe study was conducted in Ghana, a developing nation, and thus the findings and implications are peculiar to Ghana. However, the study’s findings have important practical implications for the adoption and marketing of GBCs and GBTs in other developing nations.Originality/valuePrioritizing major stimulation initiatives may be beneficial in terms of overcoming the constraints to the adoption of GBCs and GBTs in developing countries.

Artificial pancreas system (APS) is an emerging new treatment for type 1 diabetes mellitus. The aim of this study was to develop a rat APS as a research tool and demonstrate its application. We established a rat APS using Medtronic Minimed Pump 722, Medtronic Enlite sensor, and the open artificial pancreas system as a controller. We tested different dilutions of Humalog (100 units/ml) in saline ranged from 1:3 to 1:20 and determined that 1:7 dilution works well for rats with ~500g bodyweight. Blood glucose levels (BGL) of diabetic rats fed with chow diet (58% carbohydrate) whose BGL was managed by the closed-loop APS for the total duration of 207h were in euglycemic range (70–180 mg/dl) for 94.5% of the time with 2.1% and 3.4% for hyperglycemia (>180mg/dl) and hypoglycemia (<70 mg/dl), respectively. Diabetic rats fed with Sucrose pellets (94.8% carbohydrate) for the experimental duration of 175h were in euglycemic range for 61% of the time with 35% and 4% for hyperglycemia and hypoglycemia, respectively. Heathy rats fed with chow diet showed almost a straight line of BGL ~ 95 mg/dl (average 94.8 mg/dl) during the entire experimental period (281h), which was minimally altered by food intake. In the healthy rats, feeding sucrose pellets caused greater range of BGL in high and low levels but still within euglycemic range (99.9%). Next, to study how healthy and diabetic rats handle supra-physiological concentrations of glucose, we intraperitoneally injected various amounts of 50% dextrose (2, 3, 4g/kg) and monitored BGL. Duration of hyperglycemia after injection of 50% dextrose at all three different concentrations was significantly greater for healthy rats than diabetic rats, suggesting that insulin infusion by APS was superior in reducing BGL as compared to natural insulin released from pancreatic β-cells. Ex vivo studies showed that islets isolated from diabetic rats were almost completely devoid of pancreatic β-cells but with intact α-cells as expected. Lipid droplet deposition in the liver of diabetic rats was significantly lower with higher levels of triacylglyceride in the blood as compared to those of healthy rats, suggesting lipid metabolism was altered in diabetic rats. However, glycogen storage in the liver determined by Periodic acid-Schiff staining was not altered in diabetic rats as compared to healthy rats. A rat APS may be used as a powerful tool not only to study alterations of glucose and insulin homeostasis in real-time caused by diet, exercise, hormones, or antidiabetic agents, but also to test mathematical and engineering models of blood glucose prediction or new algorithms for closed-loop APS.

Diabetes mellitus significantly increases the risk of severe complications from influenza, necessitating targeted vaccination efforts. Despite vaccination being the most effective preventive measure, coverage remains below the World Health Organization's targets, partly due to limited awareness among patients. This study evaluated a digital health intervention aimed at improving influenza vaccination rates among adults with diabetes. This study aimed to demonstrate the effectiveness of digital health platforms in increasing vaccination rates among people with diabetes and to emphasize the impact of tailored messaging frequency on patient engagement and health behavior change. We hypothesized that digital tools providing empirical evidence of increased health risk awareness can effectively drive preventive actions. The study leveraged the Dario (Dario Health Corp) digital health platform to retrospectively analyze data from 64,904 users with diabetes assigned by the platform into three groups: (1) Group A received previously studied monthly flu nudge messages; (2) Group B received an adapted intervention with 2-3 monthly messages; (3) Group C served as the control with no intervention. Surveys were conducted at baseline, 3 months, and 6 months to assess vaccination status, awareness of influenza risks, and recollection of educational content. Statistical analyses, including logistic regression, chi-square tests, and t tests, were used to evaluate differences between groups. Out of 64,904 users, 8431 completed the surveys. Vaccination rates were 71.0% in group A, 71.9% in group B, and 70.5% in group C. Group B showed significantly higher awareness of influenza risks compared with the control group odds ratio (OR; OR 1.35, 95% CI 1.12-1.63; P=.001), while group A did not (OR 1.10, 95% CI 0.92-1.32; P=.27). Recollection of educational content was also higher in groups A (OR 1.29, 95% CI 1.07-1.56; P=.008) and B (OR 1.92, 95% CI 1.59-2.33; P<.001) compared with the control. In addition, a significant correlation between awareness and vaccination rates was found only in group B (χ (df=1)=6.12, P=.01). The adapted digital intervention (group B) effectively increased awareness of influenza risks and recollection of educational content, which correlated with the higher trend in vaccination rates. This study demonstrates the potential of digital health tools to enhance influenza vaccination among people with diabetes by improving risk awareness and education. Further research should focus on optimizing these interventions to achieve significant improvements in vaccination uptake and overall public health outcomes. ClinicalTrials.gov NCT06840236; https://clinicaltrials.gov/study/NCT06840236.

Purpose>Green building (GB) is globally acclaimed as the most formidable solution to the adverse effects that buildings and construction activities have on the climate and environment. Nonetheless, current evidence suggests that the adoption of GB in developing countries of Sub-Saharan Africa (SSA) is at a snail’s pace and characterized by the absence of GB codes and frameworks. This paper aims to determine the current level of adoption and implementation of GB concepts and technologies in the Ghanaian construction industry (GCI).Design/methodology/approach>An exploratory method of investigation involving a quantitative approach was used to achieve the objectives of this study. A literature review was conducted, and a questionnaire survey was conducted among 292 stakeholders in the GCI. The survey data was analyzed using descriptive and inferential statistics as well as other quantitative analysis techniques.Findings>The analysis revealed that the five most applied green building technologies (GBTs) are technologies for optimizing site planning, building orientation and configuration, use of natural ventilation, integrative use of natural lighting with electric lighting systems, application of energy-efficient lighting systems and use of permeable paving: low-traffic areas. Notably, the majority of the GBTs belong to the energy-efficiency technologies category.Research limitations/implications>The findings indicate that GBTs are gaining momentum in Ghana and that there is a need for ongoing research to develop new and more environmentally friendly building technologies to aid in the preservation of our society and natural resources to achieve United Nations Sustainable Development Goals (UN SDGs) 12 and 13.Originality/value>In effect, this study will enhance the awareness of GB development and contribute to the GB body of knowledge, particularly in the context of developing countries. It would also be useful to the GCI’s contribution to achieving the UN SDGs.

Acute ischemic stroke (AIS) is a potent trigger of immunosuppression, resulting in increased infection risk. While thrombolytic therapy with tissue-type plasminogen activator (t-PA) is still the only pharmacological treatment for AIS, plasmin, the effector protease, has been reported to suppress dendritic cells (DCs), known for their potent antigen-presenting capacity. Accordingly, in the major group of thrombolyzed AIS patients who fail to reanalyze (>60%), t-PA might trigger unintended and potentially harmful immunosuppressive consequences instead of beneficial reperfusion. To test this hypothesis, we performed an exploratory study to investigate the immunomodulatory properties of t-PA treatment in a mouse model of ischemic stroke. C57Bl/6J wild-type mice and plasminogen-deficient (plg ) mice were subjected to middle cerebral artery occlusion (MCAo) for 60 min followed by mouse t-PA treatment (0.9 mg/kg) at reperfusion. Behavioral testing was performed 23 h after occlusion, pursued by determination of blood counts and plasma cytokines at 24 h. Spleens and cervical lymph nodes (cLN) were also harvested and characterized by flow cytometry. MCAo resulted in profound attenuation of immune activation, as anticipated. t-PA treatment not only worsened neurological deficit, but further reduced lymphocyte and monocyte counts in blood, enhanced plasma levels of both IL-10 and TNFα and decreased various conventional DC subsets in the spleen and cLN, consistent with enhanced immunosuppression and systemic inflammation after stroke. Many of these effects were abolished in plg mice, suggesting plasmin as a key mediator of t-PA-induced immunosuppression. t-PA, via plasmin generation, may weaken the immune response post-stroke, potentially enhancing infection risk and impairing neurological recovery. Due to the large number of comparisons performed in this study, additional pre-clinical work is required to confirm these significant possibilities. Future studies will also need to ascertain the functional implications of t-PA-mediated immunosuppression for thrombolyzed AIS patients, particularly for those with failed recanalization.

Insulin Regulation of Skeletal Muscle PDK4 mRNA Expression Is Impaired in Acute Insulin-Resistant States Young I. Kim , Felix N. Lee , Woo S. Choi , Sarah Lee and Jang H. Youn From the Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California Address correspondence and reprint requests to Jang H. Youn, Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, 1333 San Pablo St., MMR 626, Los Angeles, CA 90089-9142. E-mail: youn{at}usc.edu Abstract We previously showed that insulin has a profound effect to suppress pyruvate dehydrogenase kinase (PDK) 4 expression in rat skeletal muscle. In the present study, we examined whether insulin’s effect on PDK4 expression is impaired in acute insulin-resistant states and, if so, whether this change is accompanied by decreased insulin’s effects to stimulate Akt and forkhead box class O (FOXO) 1 phosphorylation. To induce insulin resistance, conscious overnight-fasted rats received a constant infusion of Intralipid or lactate for 5 h, while a control group received saline infusion. Following the initial infusions, each group received saline or insulin infusion ( n = 6 or 7 each) for an additional 5 h, while saline, Intralipid, or lactate infusion was continued. Plasma glucose was clamped at basal levels during the insulin infusion. Compared with the control group, Intralipid and lactate infusions decreased glucose infusion rates required to clamp plasma glucose by ∼60% ( P < 0.01), confirming the induction of insulin resistance. Insulin’s ability to suppress PDK4 mRNA level was impaired in skeletal muscle with Intralipid and lactate infusions, resulting in two- to threefold higher PDK4 mRNA levels with insulin ( P < 0.05). Insulin stimulation of Akt and FOXO1 phosphorylation was also significantly decreased with Intralipid and lactate infusions. These data suggest that insulin’s effect to suppress PDK4 gene expression in skeletal muscle is impaired in insulin-resistant states, and this may be due to impaired insulin signaling for stimulation of Akt and FOXO1 phosphorylation. Impaired insulin’s effect to suppress PDK4 expression may explain the association between PDK4 overexpression and insulin resistance in skeletal muscle. FFA, free fatty acid FOXO, forkhead box class O GIR, glucose infusion rate PDK, pyruvate dehydrogenase kinase PI3K, phosphatidylinositol 3-kinase PPAR, peroxisome proliferator–activated receptor Footnotes Y.I.K. and F.N.L. contributed equally to this work. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement‘ in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted May 22, 2006. Received December 12, 2005. DIABETES