Investigating the physiological role of hypothalamic glucokinase in appetite and glucose homeostasis

The brain relies on glucose as a source of energy. Mechanisms that promote the taste-independent intake of glucose have been proposed but not demonstrated. The arcuate nucleus (ARC) of the hypothalamus plays a critical role in regulating energy homoeostasis. It acts as a metabolic sensing unit responding to diverse signals, including glucose, to regulate appetite. Glucokinase is a glucose-sensing enzyme expressed in the ARC. The work in this thesis aims to investigate the physiological role of ARC glucokinase in energy homoeostasis. Recombinant adeno-associated virus (rAAV) expressing the pancreatic form of rat glucokinase mRNA (rAAV-GKS) was stereotactically delivered to the ARC of male Wistar rats (iARC-GKS). This approach specifically increased glucokinase activity in the ARC as compared to control rats (iARC-GFP). Pharmacological and genetic increase in ARC glucokinase activity resulted in a significant increase in food intake. Longitudinal experiments demonstrated that this food intake resulted in a significant increase in body weight and adiposity on normal chow and high-energy diets. Further work demonstrated that ARC glucokinase specifically promotes the intake of glucose, but not of fructose, and that the orexigenic effect of ARC glucokinase is driven by specific increase in appetite for glucose. Similar changes in glucose appetite and food intake were demonstrated to occur with alterations in ARC ATP-sensitive potassium (KATP) channel activation. Glucose-stimulated NPY release was increased with increased ARC glucokinase activity. This suggests that ARC glucokinase mediates its orexigenic glucose appetite promoting effects in part via altered KATP channel activation and NPY release, which is consistent with previous work. This work identifies ARC glucokinase as a regulator of glucose appetite and glucose appetite as an important driver of food intake. ARC glucokinase may represent the brain mechanism regulating the taste-independent intake of glucose and may underlie the phenomena of ‘sweet tooth’ and ‘carbohydrate craving’

Origins of chromosomal rearrangement hotspots in the human genome: evidence from the AZFa deletion hotspots.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: The origins of the recombination hotspots that are a common feature of both allelic and non-allelic homologous recombination in the human genome are poorly understood. We have investigated, by comparative sequencing, the evolution of two hotspots of non-allelic homologous recombination on the Y chromosome that lie within paralogous sequences known to sponsor deletions resulting in male infertility. RESULTS: These recombination hotspots are characterized by signatures of concerted evolution, which indicate that gene conversion between paralogs has been predominant in shaping their recent evolution. By contrast, the paralogous sequences that surround the hotspots exhibit little evidence of gene conversion. A second feature of these rearrangement hotspots is the extreme interspecific sequence divergence (around 2.5%) that places them among the most divergent orthologous sequences between humans and chimpanzees. CONCLUSIONS: Several hominid-specific gene conversion events have rendered these hotspots better substrates for chromosomal rearrangements in humans than in chimpanzees or gorillas. Monte Carlo simulations of sequence evolution suggest that extreme sequence divergence is a direct consequence of gene conversion between paralogs. We propose that the coincidence of signatures of concerted evolution and recurrent breakpoints of chromosomal rearrangement (mapped at the sequence level) may enable the identification of putative rearrangement hotspots from analysis of comparative sequences from great apes

Fasting with adrenal insufficiency: practical guidance for healthcare professionals managing patients on steroids during Ramadan

There are limited recommendations for fasting in many chronic diseases such as adrenal insufficiency (AI). Research in such situations highlights potential for complications and need for education for patients with AI undertaking fasting during Ramadan. This article aims to provide up‐to‐date guidance for healthcare professionals to educate, discuss and manage patients with AI who are considering fasting in Ramadan and is religiously compatible. Latest guidance on this topic and the evidence base for steroid dosing are reviewed and discussed. Risk stratification for patients with AI and optimal strategies for management, including steroid dosing, are detailed. Our review highlights that patients with AI wishing to fast should undergo a thorough risk assessment ideally several months before Ramadan. ‘High risk’ and ‘Very high risk’ patients should be encouraged to explore alternative options to fasting discussed below. Prior to the commencement of Ramadan, all patients must receive up‐to‐date education on sick day rules, instructions on when to terminate their fast or abstain from fasting, carry steroid warning information and must have a valid intramuscular (IM) hydrocortisone pack and know how to administer this. Switching patients with AI desiring to fast from multiple daily hydrocortisone replacement to prednisolone 5 mg once daily at dawn (during Suhoor or Sehri) is recommended and discussed. Patients on fludrocortisone for AI should be advised to take their total dose at dawn. We provide practically relevant case‐based scenarios to help with the application of this guidance. Future efforts need to focus on healthcare professional awareness and further research in this setting

Enhancing corporate governance quality through mergers and acquisitions

This study examines whether the pre‐deal target‐bidder firm governance gap affects the bidder's postdeal change in governance quality. We estimate cross‐sectional regressions using mergers and acquisitions from 2004 to 2016. We find that the bidder's firm‐level governance improves for acquisitions where the target's governance quality is better than that of the bidder preacquisition. We attribute the results to reverse portability, suggesting that the predeal governance gap creates space for governance transfer, and bidders can adopt better governance of targets after the acquisition. Board independence, audit committee independence, CEO‐Chairman separation, stock compensation, and equal treatment of minority shareholders serve as potential channels to demonstrate the bidder's higher governance after the acquisition. Our findings also reveal that bidders with governance improvement are also associated with higher operating performance. We extend the portability theory of Ellis et al. (2017) and suggest that governance can also travel from targets to bidders through mergers and acquisitions

Diabetes, driving and fasting during Ramadan:the interplay between secular and religious law

A large proportion of the Muslim population fasts during Ramadan. The risk of hypoglycemia is increased with fasting during Ramadan in people with diabetes who are on insulin and insulin secretagogues. Therefore, the combination of fasting with diabetes and driving presents a challenging situation, with legal implications for such individuals and their healthcare professionals. This novel, narrative, non-systematic review discusses the importance of addressing hypoglycemia in fasting with reference to secular legal guidance on driving with diabetes. We discuss religious aspects relating to fasting and driving in Islam. While there is no clear guidance or legal position on diabetes and driving for individuals who are fasting, Islamic law provides a logical framework to address this. Healthcare professionals need to raise and facilitate discussions on this often-overlooked topic with people with diabetes who are planning on fasting to minimize the potential for public harm. For some individuals fasting perhaps should be avoided when driving and that this religiously compatible position would best be adopted when one is dependent on driving for livelihood. Ultimately further research on glycemic control and management when fasting and driving, as well as a formal legal guidance on this topic, is required to safeguard healthcare professionals and the public from the potential dangers of driving with diabetes and fasting

Real‐world evidence on clinical outcomes of people with type 1 diabetes using open‐source and commercial automated insulin dosing systems: A systematic review

Aims: Several commercial and open-source automated insulin dosing (AID) systems have recently been developed and are now used by an increasing number of people with diabetes (PwD). This systematic review explored the current status of real-world evidence on the latest available AID systems in helping to understand their safety and effectiveness. Methods: A systematic review of real-world studies on the effect of commercial and open-source AID system use on clinical outcomes was conducted employing a devised protocol (PROSPERO ID 257354). Results: Of 441 initially identified studies, 21 published 2018-2021 were included: 12 for Medtronic 670G; one for Tandem Control-IQ; one for Diabeloop DBLG1; two for AndroidAPS; one for OpenAPS; one for Loop; three comparing various types of AID systems. These studies found that several types of AID systems improve Time-in-Range and haemoglobin A1c (HbA1c ) with minimal concerns around severe hypoglycaemia. These improvements were observed in open-source and commercially developed AID systems alike. Conclusions: Commercially developed and open-source AID systems represent effective and safe treatment options for PwD of several age groups and genders. Alongside evidence from randomized clinical trials, real-world studies on AID systems and their effects on glycaemic outcomes are a helpful method for evaluating their safety and effectiveness

ZnO Nano-Flowers Assembled on Carbon Fiber Textile for High-Performance Supercapacitor’s Electrode

Herein, a crystalline nano-flowers structured zinc oxide (ZnO) was directly grown on carbon fiber textile (CFT) substrate via a simple hydrothermal process and fabricated with a binder-free electrode (denoted as ZnO@CFT) for supercapacitor (SC) utilization. The ZnO@CFT electrode revealed a 201 F·g−1 specific capacitance at 1 A·g−1 with admirable stability of >90% maintained after 3000 cycles at 10 A·g−1. These impressive findings are responsible for the exceedingly open channels for well-organized and efficient diffusion of effective electrolytic conduction via ZnO and CFT. Consequently, accurate and consistent structural and morphological manufacturing engineering is well regarded when increasing electrode materials’ effective surface area and intrinsic electrical conduction capability. The crystalline structure of ZnO nano-flowers could pave the way for low-cost supercapacitors

Design and Implementation of Real-Time Kitchen Monitoring and Automation System Based on Internet of Things

Automation can now be found in nearly every industry. However, home automation has yet to reach Pakistan. This paper presents an Internet of Things smart kitchen project that includes automation and monitoring. In this project, a system was developed that automatically detects the kitchen temperature. It also monitors the humidity level in the kitchen. This system includes built-in gas detection sensors that detect any gas leaks in the kitchen and notify the user if the gas pressure in the kitchen exceeds a certain level. This system also allows the user to remotely control appliances such as freezers, ovens, and air conditioners using a mobile phone. The user can control gas levels using their phone with this system. In this paper, the ESP32, DHT11 Sensor, 5 V Relay X 8, and MQ-135 gas sensors create a smart kitchen by controlling the temperature, managing humidity, and detecting gas leakage. The system was built on an Arduino board that is connected to the Internet. The hardware was integrated and programmed using an Arduino, and a user Android application was developed. The project’s goal is to allow any Android smartphone to remotely control devices. This method is commonly used in homes, businesses, and grocery stores. Users will be able to control all of their instruments from anywhere, including switches, fans, and lights. Furthermore, simulation was performed using Matlab2016b on multiple houses. In the simulation, not only was the kitchen considered, but also two, four, and six houses. Each house has two bedrooms, one living room, one guest room, two bathrooms, and one kitchen. The results revealed that using this system will have a scientifically significant impact on electricity consumption and cost. In the case of the houses, the cost was USD 33.32, 32.64, 22.32, and 19.54 for unscheduled, two, four, and six houses, respectively. Thus, it was observed that the cost and power are directly proportional to each other. The results reveal that the proposed solution efficiently reduces the cost as compared to that of unscheduled houses.publishedVersio