Obesity Treatments to Improve Type 1 Diabetes (OTID): a randomized controlled trial of the combination of glucagon-like peptide 1 analogues and sodium-glucose cotransporter 2 inhibitors—protocol for Obesity Treatments to Improve Type 1 Diabetes (the OTID trial)

Background: The guidelines of the American Diabetes Association and European Association for the Study of Diabetes suggest that patients with obesity type 2 diabetics and chronic kidney disease need either glucagon-like peptide 1 receptor analogues or sodium-glucose cotransporter-2 inhibitors. If neither achieve metabolic control, then the recommendation is to combine both drugs. The evidence base for combining glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors is not well researched, and hence, the impact of the guidelines is limited. The aim of this randomized controlled trial is to test the impact of the combination of glucagon-like peptide 1 receptor analogues/sodium-glucose cotransporter-2 inhibitors on body weight and kidney damage, in patients with type 1 diabetes and chronic kidney disease. In addition, we will explore the associated changes in the metabolic pathways with each of the treatments used in this randomized controlled trial. Methods: In this 6-month randomized control trial, 60 participants aged between 21 and 65 years, with a body mass index above 25 kg/m2, and type 1 diabetics with chronic kidney disease will be randomized to receive 1 of 5 possible treatments: (1) standard care (control), (2) glucagon-like peptide 1 receptor analogues alone, (3) sodium-glucose cotransporter-2 inhibitors alone, (4) combination of glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors and (5) combination of glucagonlike peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors with intensive lifestyle advice. The primary objective will be the percentage change in total body weight from baseline at 6 months. The secondary objectives are to compare the change in glycaemia; blood pressure; dyslipidaemia; albuminuria; proportion of participants reaching weight loss of ≥ 5%, ≥ 10% and ≥ 15%; and change in BMI (kg/m2) from baseline and change in waist circumference (cm). All the experiments will be conducted at the Dasman Diabetes Institute after approval from the local research and ethics committee. Discussion: The present randomized controlled trial aims to investigate the impact of the combination of glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors on body weight and kidney damage in patients with type 1 diabetes mellitus and chronic kidney disease, as well as exploring the associated changes in the metabolic pathways with each of the treatments used. This study addresses the current gap in the evidence base regarding the combination of these two drugs, which is particularly relevant given the American Diabetes Association and European Association for the Study of Diabetes guidelines recommending their combined use for patients with obesity, type 2 diabetes, and chronic kidney disease who do not achieve metabolic control with either drug alone. Trial registration: ClinicalTrials.gov Identifier: NCT05390307 Trial registration date - 25th May 202

Time-delayed effects of a single application of AgNPs on structure of testes and functions in Blaps polychresta Forskal, 1775 (Coleoptera: Tenebrionidae)

Silver nanoparticles (AgNPs) are currently themost frequently used engineered nanoparticles. The penetration of AgNPs into ecosystems is undeniable, and their adverse effects on organismreproduction are of fundamental importance for ecosystem stability. In this study, the survival time of the Egyptian beetle Blaps polychresta Forskal, 1775 (Coleoptera: Tenebrionidae), after a single application of 7 different doses,was calculated for 30 days. Then, for the group for which the effect on mortality was calculated as LOAEL - the Lowest Observed Adverse Effect Level, namely, 0.03 mg AgNPs/g body weight (b.w.t.), the following were assessed: structure and ultrastructure of gonads by TEM and SEM, cell viability by cytometry, DNA damage by the comet assay, and a variety of stress markers by spectrophotometric methods. A dose-dependent reduction in the survival time of the insects wa

Reduced body length and morphological disorders in Chrysomya albiceps (Diptera: Calliphoridae) larvae reared on aluminum phosphide-treated rabbits

Assessing the time of death based on the growth and development of insects is a critical task in forensic entomology. The rate of larvae development can be affected by a variety of toxins, including pesticides. Aluminum phosphide (AlP) is a low-cost insecticide that has yet to be tested for entomotoxicological significance, despite the fact that it is frequently the cause of fatal poisoning. In this study, we measured the body length of Chrysomya albiceps larvae reared on the carcasses of rabbits poisoned with AlP and analyzed the morphological changes of the larvae reared on the carcasses of rabbits poisoned with AlP. The concentration of AlP in the body of the larvae was significantly lower than in rabbit tissues. Insects from the AlP group had a significantly lower gain in body length. Furthermore, deformities in the larvae were found. Smaller respiratory spiracles were found, as well as a deformed small posterior end with hypogenesis of the posterior respiratory spiracles. Thus, disturbed growth and development of carrion flies found at a crime scene could indicate pesticide poisoning, such as aluminum phosphide

Nerve growth factor, neuropeptides and cutaneous nerves in atopic dermatitis

Introduction: Neurogenic components, as neurotrophic factors and neuropeptides, are probably involved in the pathogenesis of atopic dermatitis (AD) with the neuroimmunocutaneous system as they modify the functions of immunoactive cells in the skin. Nerve growth factor (NGF) is the best-characterized member of the neurotrophin family. Both NGF and neuropeptides (NPs) may be associated with the disease pathogenesis. Aim: This study aims to evaluate the plasma level of NGF and NPs in AD patients and correlate them with the disease activity and nerve changes in the skin by electron microscopy. Materials and Methods: Plasma levels of NGF and vasoactive intestinal peptide (+VIP) were measured by an immunoenzymatic assay while plasma levels of calcitonine gene related peptide (CGRP) and neuropeptide Y (NPY) were measured by radioimmunoassay in 30 AD patients in comparison to 10 normal non-atopic controls. Electron microscopic study was done in 10 AD patients. Results: It has been found that there is significant increase of plasma levels of NGF and NPs in AD patients compared with controls. There is a positive correlation between the plasma levels of NGF and disease activity (correlation coefficient = 0.750, P< 0.005). There is a significant correlation between the number of Schwann axon complex, evidenced by electron microscopic examination and plasma level of NGF in AD patients. Conclusion: It has been concluded that these neurogenic factors; NGF and NPs modulate the allergic response in AD, probably through interactions with cells of the immune-inflammatory component. NGF might be considered as a marker of the disease activity

UPLC-MS/MS Analysis of Naturally Derived Apis mellifera Products and Their Promising Effects against Cadmium-Induced Adverse Effects in Female Rats

Honeybee products arouse interest in society due to their natural origin and range of important biological properties. Propolis (P) and royal jelly (RJ) attract scientists' attention because they exhibit antioxidant, anti-inflammatory, anti-bacterial, anti-tumor, and immunomodulatory abilities. In this study, we tested whether P and RJ could mitigate the adverse effects of cadmium (Cd) exposure, with particular emphasis on the reproductive function in female rats. In this line, one week of pretreatment was established. Six experimental groups were created, including (i) the control group (without any supplementation), (ii) the Cd group (receiving CdCl2 in a dose of 4.5 mg/kg/day), (iii) the P group (50 mg of P/kg/day), (iv) RJ group (200 mg of RJ/kg/day), (v) P + Cd group (rats pretreated with P and then treated with P and Cd simultaneously), (vi) RJ + Cd group (animals pretreated with RJ before receiving CdCl2 simultaneously with RJ). Cd treatment of rats adversely affected a number of measured parameters, including body weight, ovarian structure and ultrastructure, oxidative stress parameters, increased ovarian Cd content and prolonged the estrous cycle. Pretreatment and then cotreatment with P or RJ and Cd alleviated the adverse effects of Cd, transferring the clusters in the PCA analysis chart toward the control group. However, clusters for cotreated groups were still distinctly separated from the control and P, or RJ alone treated groups. Most likely, investigated honeybee products can alter Cd absorption in the gut and/or increase its excretion through the kidneys and/or mitigate oxidative stress by various components. Undoubtedly, pretreatment with P or RJ can effectively prepare the organism to overcome harmful insults. Although the chemical composition of RJ and P is relatively well known, focusing on proportion, duration, and scheme of treatment, as well as the effects of particular components, may provide interesting data in the future. In the era of returning to natural products, both P and RJ seem valuable materials for further consideration as anti-infertility agents

UPLC-MS/MS Analysis of Naturally Derived <i>Apis mellifera</i> Products and Their Promising Effects against Cadmium-Induced Adverse Effects in Female Rats

Honeybee products arouse interest in society due to their natural origin and range of important biological properties. Propolis (P) and royal jelly (RJ) attract scientists’ attention because they exhibit antioxidant, anti-inflammatory, anti-bacterial, anti-tumor, and immunomodulatory abilities. In this study, we tested whether P and RJ could mitigate the adverse effects of cadmium (Cd) exposure, with particular emphasis on the reproductive function in female rats. In this line, one week of pretreatment was established. Six experimental groups were created, including (i) the control group (without any supplementation), (ii) the Cd group (receiving CdCl2 in a dose of 4.5 mg/kg/day), (iii) the P group (50 mg of P/kg/day), (iv) RJ group (200 mg of RJ/kg/day), (v) P + Cd group (rats pretreated with P and then treated with P and Cd simultaneously), (vi) RJ + Cd group (animals pretreated with RJ before receiving CdCl2 simultaneously with RJ). Cd treatment of rats adversely affected a number of measured parameters, including body weight, ovarian structure and ultrastructure, oxidative stress parameters, increased ovarian Cd content and prolonged the estrous cycle. Pretreatment and then cotreatment with P or RJ and Cd alleviated the adverse effects of Cd, transferring the clusters in the PCA analysis chart toward the control group. However, clusters for cotreated groups were still distinctly separated from the control and P, or RJ alone treated groups. Most likely, investigated honeybee products can alter Cd absorption in the gut and/or increase its excretion through the kidneys and/or mitigate oxidative stress by various components. Undoubtedly, pretreatment with P or RJ can effectively prepare the organism to overcome harmful insults. Although the chemical composition of RJ and P is relatively well known, focusing on proportion, duration, and scheme of treatment, as well as the effects of particular components, may provide interesting data in the future. In the era of returning to natural products, both P and RJ seem valuable materials for further consideration as anti-infertility agents

Protocol for a randomised controlled trial to investigate the effect of home and gym-based resistance exercise training on glycaemic control, body composition and muscle strength

Background Resistance exercise is known to be effective in reducing glycated haemoglobin (HbA1c) in people with type 2 diabetes. However, studies, so far, have employed supervised resistance exercise in a laboratory or gym facility which limits the future translation of such exercise in to clinical practice and recommendations. Our primary aim, therefore, is to test the hypothesis, in a randomized controlled trial, that home-based resistance exercise training and gym-based resistance exercise training both reduce HbA1c levels in people with type 2 diabetes compared to control. We will also investigate the effects of home- and gym-based resistance exercise training on muscle strength and body composition. Methods The current study is a three-arm randomised controlled trial which will be conducted with 150 eligible people with type 2 diabetes to compare home-and gym-based resistance exercise training with usual care in Kuwait. The interventions will be delivered by exercise specialists and last for 32 weeks. The primary outcomes are HbA1c with secondary outcomes measuring muscle function, body composition, physical activity and quality of life. Discussion Ethical approval has been granted by the Dasman Diabetes Institute ethical review committee (RA/197/2019). Study findings will be disseminated through presentation at scientific conferences and in scientific journals