The role of hypothalamic H1 receptor antagonism in antipsychotic-induced weight gain

Treatment with second generation antipsychotics (SGAs), notably olanzapine and clozapine, causes severe obesity side effects. Antagonism of histamine H1 receptors has been identified as a main cause of SGA-induced obesity, but the molecular mechanisms associated with this antagonism in different stages of SGA-induced weight gain remain unclear. This review aims to explore the potential role of hypothalamic histamine H1 receptors in different stages of SGA-induced weight gain/obesity and the molecular pathways related to SGA-induced antagonism of these receptors. Initial data have demonstrated the importance of hypothalamic H1 receptors in both short- and long-term SGA-induced obesity. Blocking hypothalamic H1 receptors by SGAs activates AMP-activated protein kinase (AMPK), a well-known feeding regulator. During short-term treatment, hypothalamic H1 receptor antagonism by SGAs may activate the AMPK—carnitine palmitoyltransferase 1 signaling to rapidly increase caloric intake and result in weight gain. During long-term SGA treatment, hypothalamic H1 receptor antagonism can reduce thermogenesis, possibly by inhibiting the sympathetic outflows to the brainstem rostral raphe pallidus and rostral ventrolateral medulla, therefore decreasing brown adipose tissue thermogenesis. Additionally, blocking of hypothalamic H1 receptors by SGAs may also contribute to fat accumulation by decreasing lipolysis but increasing lipogenesis in white adipose tissue. In summary, antagonism of hypothalamic H1 receptors by SGAs may time-dependently affect the hypothalamus-brainstem circuits to cause weight gain by stimulating appetite and fat accumulation but reducing energy expenditure. The H1 receptor and its downstream signaling molecules could be valuable targets for the design of new compounds for treating SGA-induced weight gain/obesity

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Model Predictive Control with Direct Feedthrough with Application on a Mist Reactor

Theoretical derivation of a controller formulation for systems with direct feedthrough from the input to the output is considered. The resulting model predictive control (MPC) scheme requires the use of a predictor for the output. Two forms of predictor are compared. This work opens up the possibility of applying MPCs to practical systems with direct feedthrough. The controller is applied to a multivariable mist reactor for cell culture. A linear parameter-varying (LPV) model is applied with the controller. This enables the controller to have low computational complexity and high accuracy in controlling the temperature and humidity in the reactor. With the successful implementation of the LPV model to the controller, the proposed MPC scheme with direct feedthrough is shown to be feasible for application in practical systems

Author Correction: Double-negative metamaterial square enclosed Q.S.S.R For microwave sensing application in S-band with high sensitivity and Q-factor

Correction to: Scientific Reports https://doi.org/10.1038/s41598-023-34514-z, published online 05 May 2023 The original version of this Article contained an error in Affiliation 4, which was incorrectly given as ‘Department of Electrical Engineering, Faculty of Engineering, Taif University, Taif, 21944, Saudi Arabia’. The correct affiliation is listed below: Department of Electrical Engineering, College of Engineering, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia. The original Article has been corrected

Cross enclosed square split ring resonator based on D.N.G. metamaterial absorber for X-band glucose sensing application

This article presents a novel real-time meta-material (MM) sensor based on a non-invasive method that operates in microwave frequency ranges at 8.524 GHz to measure blood glucose levels with quality factor 184 is designed and fabricated. A cross enclosed between two square shapes produces a strong interaction between glucose samples and electromagnetic waves. In this study, 5 were tested noninvasively using the proposed glucose resonant sensor with a range of glucose-level changes from 50 to 130 mg/dL. For this range of glucose-level changes, the frequency detection resolution is 5.06 MHz/(mg/dL), respectively. Despite simulations, fabrication procedures (F.P.) have been carried out for more precise result verification. For the purpose of qualitative analysis, the proposed MM sensor is considered a viable candidate for determining glucose levels

Double-negative metamaterial square enclosed Q.S.S.R For microwave sensing application in S-band with high sensitivity and Q-factor

Abstract Metamaterials have gained much attention due to their exciting characteristics and potential uses in constructing valuable technologies. This paper presents a double negative square resonator shape metamaterial sensor to detect the material and its thickness. An innovative double-negative metamaterial sensor for microwave sensing applications is described in this paper. It has a highly sensitive Q-factor and has good absorption characteristics approximately equal to one. For the metamaterial sensor, the recommended measurement is 20 by 20 mm. Computer simulation technology (C.S.T.) microwave studios are used to design the metamaterial structure and figure out its reflection coefficient. Various parametric analyses have been performed to optimize the design and size of the structure. The experimental and theoretical results are shown for a metamaterial sensor that is attached to five different materials such as, Polyimide, Rogers RO3010, Rogers RO4350, Rogers RT5880, and FR-4. A sensor’s performance is evaluated using three different thicknesses of FR-4. There is a remarkable similarity between the measured and simulated outcomes. The sensitivity values for 2.88 GHz and 3.5 GHz are 0.66% and 0.19%, respectively, the absorption values for both frequencies are 99.9% and 98.9%, respectively, and the q-factor values are 1413.29 and 1140.16, respectively. In addition, the figure of merit (FOM) is analyzed, and its value is 934.18. Furthermore, the proposed structure has been tested against absorption sensor applications for the purpose of verifying the sensor's performance. With a high sense of sensitivity, absorption, and Q-factor, the recommended sensor can distinguish between thicknesses and materials in various applications