Comparative effectiveness of Roux-en-Y gastric bypass and sleeve gastrectomy in achieving diabetes remission in patients with diabetes-related vascular diseases: A multicentred study.

Metabolic and bariatric surgeries (MBS), including Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG), have proven effective in promoting long-term diabetes remission among patients with type-2 diabetes (T2D). In this multicentre retrospective cohort study, we investigated the effectiveness of RYGB and SG in achieving diabetes remission, specifically among patients with T2D and vascular complications, while accounting for similar baseline diabetes severity. Although various scores predict diabetes remission after bariatric surgery, they do not consider diabetes-related vascular complications, which can influence outcomes even in patients with similar baseline T2D severity.

Improving the prediction of chemotherapy dose-limiting toxicity in colon cancer patients using an AI-CT-based 3D body composition of the entire L1-L5 lumbar spine.

Purpose: Chemotherapy dose-limiting toxicities (DLT) pose a significant challenge in successful colon cancer treatment. Body composition analysis may enable tailored interventions thereby supporting the mitigation of chemotherapy toxic effects. This study aimed to evaluate and compare the effectiveness of using three-dimensional (3D) CT body composition measures from the entire lumbar spine levels (L1-L5) versus a single vertebral level (L3), the current gold standard, in predicting chemotherapy DLT in colon cancer patients.

Paclitaxel-induced peripheral neuropathy in male rats attenuated by calmangafodipir, a superoxide dismutase mimetic.

Paclitaxel induces peripheral neuropathy, which is considered a dose-limiting factor. However, appropriate prophylactic agents are currently unavailable. We investigated the prophylactic effects of calmangafodipir, a superoxide dismutase mimetic, on paclitaxel-induced peripheral neuropathy using a male rat model.

Okanin alleviates symptoms of nociceptive-like responses in diabetic peripheral neuropathy in type 1 diabetic Wistar rats by regulating the AGEs/NF-κB/Nrf-2 pathway.

Elevated reactive species and AGEs contribute to deregulation of transcription factors e.g., NF-κB and Nrf2 in diabetic peripheral neuropathy (DPN).

Muscarinic acetylcholine type 1 receptor antagonism activates TRPM3 to augment mitochondrial function and drive axonal repair in adult sensory neurons.

Objective: Antagonism of the muscarinic acetylcholine type 1 receptor (MR) promotes sensory axon repair and is protective in peripheral neuropathy, however, the mechanism remains elusive. We investigated the role of the heat-sensing transient receptor potential melastatin-3 (TRPM3) cation channel in MR antagonism-mediated nerve regeneration and explored the potential of TRPM3 activation to facilitate axonal plasticity.

Methods: Dorsal root ganglion (DRG) neurons from adult control or diabetic rats were cultured and treated with TRPM3 agonists (CIM0216, pregnenolone sulfate) and MR antagonists pirenzepine (PZ) or muscarinic toxin 7 (MT7).

CMT2 and distal hereditary motor neuropathy associated with VRK1 variants: Case series.

Axonal Charcot-Marie-Tooth disease (CMT2) and distal hereditary motor neuropathy (dHMN) are associated with a heterogeneous group of genes encoding proteins that are involved in axonal transport, control of RNA metabolism, mitochondrial dynamics and DNA repair. VRK1 (vaccinia-related kinase 1) is a serine/threonine kinase which is widely expressed in human tissue and plays a role in RNA maturation and processing and in DNA damage response. Variants of VRK1 have been associated with neurodevelopmental and neuromuscular disorders including pontocerebellar hypoplasia, motor neuron disorders and distal hereditary motor neuropathy.

Skeletal Muscle Mass Loss and Physical Function in Young to Middle-Aged Adult Patients With Diabetes: Cross-Sectional Observational Study.

Background: Recently, it has been reported that older adults with type 2 diabetes mellitus (T2DM) have lower skeletal muscle mass than healthy individuals. Although skeletal muscle mass in older adults with diabetes is occasionally reported, similar reports on young to middle-aged adults are limited.

Objective: This study aims to assess the prevalence of skeletal muscle loss in young to middle-aged adults with diabetes, examine the relationship between skeletal muscle loss and physical function in these patients, and examine whether there are differences in these characteristics between men and women.

Consensus Recommendations for Studies of Outflow Facility and Intraocular Pressure Regulation Using Ex Vivo Perfusion Approaches.

Intraocular pressure (IOP) elevation is the primary risk factor and currently the main treatable factor for progression of glaucomatous optic neuropathy. In addition to direct clinical and living animal in vivo studies, ex vivo perfusion of anterior segments and whole eyes is a key technique for studying conventional outflow function as it is responsible for IOP regulation. We present well-tested experimental details, protocols, considerations, advantages, and limitations of several ex vivo model systems for studying IOP regulation.

Effects of on neurotransmission and expression of BDNF, tau, ACHE and BACE in diabetic rats.

Diabetes mellitus, a chronic metabolic disorder, has significant global health implications, particularly due to its neurological complications, such as diabetic neuropathy. This condition increases the risk of neurodegenerative diseases by affecting peripheral nerves and cognition. , known for its neuroprotective properties, shows promise as a therapeutic option for addressing these complications.

Herbal Approaches to Diabetes Management: Pharmacological Mechanisms and Omics-Driven Discoveries.

Diabetes mellitus is a chronic metabolic disorder marked by hyperglycemia, resistance to insulin, and impaired function of the pancreatic β-cells; it advances into more serious complications like nephropathy, neuropathy, cardiovascular disease, and retinopathy; herbal medicine has indicated promise in not just mitigating the symptoms but also in managing the complications. This review would aim to evaluate the pharmacological aspect of the botanical therapies Anacardium occidentale, Allium sativum, Urtica dioica, and Cinnamomum zeylanicum, as well as their bioactive phytochemicals, quercetin, resveratrol, berberine, and epigallocatechin gallate (EGCG). In this review, we discuss their mechanisms for secreting the insulin sensitizers, carbohydrate-hydrolyzing enzymes, reduction in oxidative stress and effectiveness against diabetic complications-all through sensitivity to insulin.

A Reduction in Mitophagy Is Associated with Glaucomatous Neurodegeneration in Rodent Models of Glaucoma.

Glaucoma is a heterogenous group of optic neuropathies characterized by the degeneration of optic nerve axons and the progressive loss of retinal ganglion cells (RGCs), which could ultimately lead to vision loss. Elevated intraocular pressure (IOP) is a major risk factor in the development of glaucoma, and reducing IOP remains the main therapeutic strategy. Endothelin-1 (ET-1), a potent vasoactive peptide, has been shown to produce neurodegenerative effects in animal models of glaucoma.

Integration and Differentiation of Transplanted Human iPSC-Derived Retinal Ganglion Cell Precursors in Murine Retinas.

Optic neuropathy such as glaucoma, stemming from retinal ganglion cell (RGC) degeneration, is a leading cause of visual impairment. Given the substantial loss of RGCs preceding clinical detection of visual impairment, cell replacement therapy emerges as a compelling treatment strategy. Human-induced pluripotent stem cells (hiPSCs) serve as invaluable tools for exploring the developmental processes and pathological mechanisms associated with human RGCs.

Dietary Docosahexaenoic Acid-Rich Supplementation Decreases Neurotoxic Lipid Mediators in Participants with Type 2 Diabetes and Neuropathic Pain.

Background/objectives: There is increasing evidence linking circulating neurotoxic lipids to the progression of chronic neuroinflammatory diseases in the peripheral and central nervous systems. Strategies to modify lipid profiles, such as docosahexaenoic acid (DHA)-rich supplementation, may aid in managing conditions like painful diabetic neuropathy (pDN). In a previous study, we demonstrated that three months of DHA supplementation significantly altered the metabolomic profile of patients with painful diabetic neuropathy (pDN), resulting in symptom improvement.

Overexpression of Egr1 Transcription Regulator Contributes to Schwann Cell Differentiation Defects in Neural Crest-Specific Knockout Mice.

Adenosine deaminase acting on RNA 1 (ADAR1) is the principal enzyme for the adenosine-to-inosine RNA editing that prevents the aberrant activation of cytosolic nucleic acid sensors by endogenous double stranded RNAs and the activation of interferon-stimulated genes. In mice, the conditional neural crest deletion of reduces the survival of melanocytes and alters the differentiation of Schwann cells that fail to myelinate nerve fibers in the peripheral nervous system. These myelination defects are partially rescued upon the concomitant removal of the Mda5 antiviral dsRNA sensor in vitro, suggesting implication of the Mda5/Mavs pathway and downstream effectors in the genesis of mutant phenotypes.

Intranasal Treatment with Cannabinoid 2 Receptor Agonist HU-308 Ameliorates Cold Sensitivity in Mice with Traumatic Trigeminal Neuropathic Pain.

Post-traumatic trigeminal neuropathy (PTTN) is a sensory abnormality caused by injury to the trigeminal nerve during orofacial surgery. However, existing analgesics are ineffective against PTTN. Abnormal microglial activation in the caudal part of the spinal trigeminal nucleus caudal part (Sp5C), where the central trigeminal nerve terminals reside, plays an important role in PTTN pathogenesis.

Giant axonal neuropathy (GAN): cross-sectional data on phenotypes, genotypes, and proteomic signature from a German cohort.

Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease affecting the peripheral and central nervous system and is caused by bi-allelic variants in the GAN gene, leading to loss of functional gigaxonin protein. A treatment does not exist, but a first clinical trial using a gene therapy approach has recently been completed. Here, we conducted the first systematic study of GAN patients treated by German-speaking child neurologists.

Obesity, Metabolic Health, and Diabetic Complications in People With Type 1 Diabetes.

Aim: The concept of metabolically healthy obesity (MHO) has not been studied in type 1 diabetes (T1D). By analysing datasets from the DCCT/EDIC study, we compared the development of diabetic complications by obesity and metabolic health over 30 years of follow up.

Materials And Methods: Insulin resistance was calculated by estimated glucose disposal rate (eGDR).

Relevance of macrophages in the wound healing process among individuals afflicted with diabetic foot ulcers.

In this paper, we provide a commentary on an article focusing on diabetic foot ulcer (DFU) as a dreadful complication of diabetes mellitus. The development of this condition is influenced by factors such as diabetic peripheral neuropathy, lower extremity artery disease, and infection. However, the underlying mechanism remains elusive.

Targeting the neonatal Fc receptor (FcRn) is not beneficial in an animal model of chronic neuritis.

The inhibition of the neonatal Fc receptor (FcRn) is a promising therapeutic pathway in certain autoimmune disorders to reduce the amount of circulating pathogenic IgG autoantibodies by interfering with their recycling system. FcRn antibodies are currently being tested in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). This study aimed to investigate the therapeutic potential of an antibody targeting FcRn in the intracellular adhesion molecule 1 (ICAM1)-deficient NOD mouse-a model representative for many aspects of human CIDP.

The Discovery of Autoimmune Nodopathies and the Impact of IgG4 Antibodies in Autoimmune Neurology.

In the past decade, significant progress has been made on the understanding of IgG4-mediated autoimmune diseases, of both the central and the peripheral CNS. In addition to the description of diverse antigenic targets, the description of IgG subclasses associated with specific pathogenic autoantibodies has provided useful insights into the pathophysiology and, more importantly, into the therapeutic implications of the autoantibody subclasses. This understanding has affected how myasthenia gravis, autoimmune encephalitis, and autoimmune neuropathies are treated.

Lipocalin-2 as a therapeutic target for diabetes neurological complications.

Introduction: Diabetes mellitus, a chronic disorder with persistent hyperglycemia, severely affects the quality of life through significant neurological impairments, including neuropathy and cognitive dysfunction. Inflammation and oxidative stress are key factors in these complications, and Lipocalin-2 (LCN2), which is involved in inflammation and iron homeostasis, is crucial in these processes.

Area Covered: This review explores the potential of LCN2 as a therapeutic target for mitigating diabetes neurological complications.

Causal relationship between hypothyroidism and peripheral neuropathy: a Mendelian randomization study of European ancestry.

Background: Metabolic disorders are significant risk factors for peripheral neuropathy (PN) diseases. However, current clinical observational studies cannot fully determine the causal relationships between hypothyroidism (HT) and PN diseases.

Methods: We performed univariate Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) associated with hypothyroidism and two diseases clinically presented as HT (autoimmune thyroid disease and benign neoplasm of the pituitary gland and craniopharyngeal duct) as instrumental variables.

Annexin-V binds subpopulation of immune cells altering its interpretation as an biomarker for apoptosis in the retina.

In cells undergoing apoptosis phosphatidylserine, a major component of the plasma membrane, translocates to the outer leaflet where it provides eat-me signals for phagocytic recognition and is bound by annexin-V, an apoptotic marker. The need to track retinal ganglion cell death (RGC) in response to glaucomatous damage or optic neuropathy has led to the development of DARC (detection of apoptosing retinal cells) imaging, providing non-invasive, assessment of RGC death. Although the eye is an immune privileged site, resident and infiltrating immune cells are known to respond quickly to trauma or infection.

Opa1 and MT-Nd6 mutations induce early mitochondrial changes in the retina and prelaminar optic nerve of hereditary optic neuropathy mouse models.

Hereditary optic neuropathies, including dominant optic atrophy and Leber's hereditary optic neuropathy, are genetic disorders characterized by retinal ganglion cell degeneration leading to vision loss, mainly associated with mitochondrial dysfunction. In this study, we analysed mitochondrial distribution and ultrastructure in the retina and longitudinal optic nerve sections of pre-symptomatic hereditary optic neuropathies mouse models with Opa1 and Nd6 deficiency to identify early mitochondrial changes. Our results show significant mitochondrial fragmentation and increased mitophagy in mice, indicating early mitochondrial changes prior to neuronal loss.