Enhanced expression of dystrophin, IGF-1, CD44 and MYH3 in plasma and skeletal muscles including diaphragm of mdx mice after oral administration of Neu REFIX beta 1,3-1,6 glucan.

Duchenne muscular dystrophy (DMD) is a rare genetic disease, causing muscle degeneration due to lack of dystrophin with inadequate muscle regeneration culminating in muscle dysfunction. The N-163 strain of Aureobasidium Pullulans produced Beta-1,3 - 1,6-glucan (Neu REFIX) reported to be safe with anti-inflammatory and anti-fibrotic efficacy earlier, herein we evaluated its effects on muscle regeneration in mdx mice. Forty-five mice in three groups (n = 15 each): Group 1 (normal), Group 2 (mdx control), and Group 3 (mdx fed Neu REFIX) were evaluated for 45 days.

Efficacy of N-163 beta-glucan in beneficially improving biomarkers of relevance to muscle function in patients with muscular dystrophies in a pilot clinical study.

Background: Muscular dystrophies other than Duchenne muscular dystrophy (DMD) are genetic diseases characterized by increasing muscle weakness, loss of ambulation, and ultimately cardiac and respiratory failure. There are currently no effective therapeutics available. Having demonstrated the efficacy of a N-163 strain of Aureobasidium Pullulans (Neu-REFIX) produced B-1, 3-1,6-Glucan in pre-clinical and clinical studies of Duchenne muscular dystrophy (DMD) earlier, we assessed the effectiveness of this novel Beta glucan in the other muscular dystrophies in the present study.

Pulsed low-dose-rate radiation (PLDR) reduces the tumor-promoting responses induced by conventional chemoradiation in pancreatic cancer-associated fibroblasts.

Pancreatic cancer is becoming increasingly deadly, with treatment options limited due to, among others, the complex tumor microenvironment (TME). This short communications study investigates pulsed low-dose-rate radiation (PLDR) as a potential alternative to conventional radiotherapy for pancreatic cancer neoadjuvant treatment. Our ex vivo research demonstrates that PLDR, in combination with chemotherapy, promotes a shift from tumor-promoting to tumor-suppressing properties in a key component of the pancreatic cancer microenvironment we called CAFu (cancer-associated fibroblasts and selfgenerated extracellular matrix functional units).

Beneficial immune-modulatory effects of the N-163 strain of -produced 1,3-1,6 Beta glucans in Duchenne muscular dystrophy: Results of an open-label, prospective, exploratory case-control clinical study.

Background: This exploratory case-control study is to evaluate the effects of supplementation of -N-163 strain produced 1,3-1,- 6 beta glucan in young patients with Duchenne muscular dystrophy (DMD).

Methods: Twenty-seven male subjects aged 5-19 years with DMD were included, nine in the control arm and 18 in the treatment arm to receive N-163 beta glucan along with conventional therapies for 45 days. While performing the analysis, steroid usage was also taken into consideration, those not administered steroids (Steroid -ve) (Control, n = 5; treatment, n = 9), those administered steroids (Steroid +ve) (Control, n = 4; treatment, n = 9).

Setup Uncertainty of Pediatric Brain Tumor Patients Receiving Proton Therapy: A Prospective Study.

This study quantifies setup uncertainty in brain tumor patients who received image-guided proton therapy. Patients analyzed include 165 children, adolescents, and young adults (median age at radiotherapy: 9 years (range: 10 months to 24 years); 80 anesthetized and 85 awake) enrolled in a single-institution prospective study from 2020 to 2023. Cone-beam computed tomography (CBCT) was performed daily to calculate and correct manual setup errors, once per course after setup correction to measure residual errors, and weekly after treatments to assess intrafractional motion.

Third-Generation Thyrotropin Receptor Antibody (TRAb) assay for predicting neonatal thyroid dysfunction in pregnant women with Graves' disease.

Purpose: The aim is to validate the third generation Thyrotropin receptor antibody (TRAb) assay for predicting neonatal thyroid dysfunction and adverse pregnancy outcomes in pregnant women with Graves' disease.

Methods: This prospective cohort study was conducted in TRAb positive pregnant women with Graves' disease and their off springs. The primary outcome was to assess different forms of neonatal thyroid dysfunction in relation to maternal and neonatal TRAb levels.

Re-examination of therapeutic management of muscular dystrophies using a vascular smooth muscle-centered approach.

In contrast to the long-standing focus on the pathophysiology of skeletal muscles in the hunt for a cure for Duchenne muscular dystrophy (DMD), we opine that the malfunctioning of dystrophin produced by vascular smooth muscle is a major contributor to the pathology of the illness. We believe that a biological response modifier glucan (BRMG), which has been shown in clinical studies of DMD to boost the expression of vascular smooth muscle dystrophin and provide anti-fibrotic and anti-inflammatory effects, may play a key role in reducing the pathogenesis of DMD. According to the evaluation of biomarkers, this BRMG, which is safe and side-effect-free, reduces the pathogenesis of DMD.

Cooperative Deep Q-Learning Framework for Environments Providing Image Feedback.

In this article, we address two key challenges in deep reinforcement learning (DRL) setting, sample inefficiency and slow learning, with a dual-neural network (NN)-driven learning approach. In the proposed approach, we use two deep NNs with independent initialization to robustly approximate the action-value function in the presence of image inputs. In particular, we develop a temporal difference (TD) error-driven learning (EDL) approach, where we introduce a set of linear transformations of the TD error to directly update the parameters of each layer in the deep NN.

Perioperative Indications for Gabapentinoids in Pediatrics: A Narrative Review.

In recent years, there has been increased interest in using gabapentinoids (gabapentin and pregabalin) as part of multimodal medication plans or enhanced recovery after surgery protocols to mitigate several perioperative clinical challenges. Outcomes explored in the context of using gabapentinoids perioperatively in children are variable and include acute complications of pain, anxiety, nausea and vomiting, and emergence agitation, as well as the long-term postoperative outcome of chronic postsurgical pain. This narrative review describes the current literature regarding perioperative use of gabapentinoids in pediatric patients and aims to describe the role of gabapentinoids in the perioperative setting for each specific indication.

NetrinG1 cancer-associated fibroblasts generate unique extracellular vesicles that support the survival of pancreatic cancer cells under nutritional stress.

It is projected that in 5 years, pancreatic cancer will become the second deadliest cancer in the United States. A unique aspect of pancreatic ductal adenocarcinoma (PDAC) is its stroma; rich in cancer-associated fibroblasts (CAFs) and a dense CAF-generated extracellular matrix (ECM). These pathogenic stroma CAF/ECM units cause the collapse of local blood vessels rendering the tumor microenvironment nutrient-poor.

Two unique biological response-modifier glucans beneficially regulating gut microbiota and faecal metabolome in a non-alcoholic steatohepatitis animal model, with potential applications in human health and disease.

Objective: The gut microbiome and its metabolites are influenced by age and stress and reflect the metabolism and health of the immune system. We assessed the gut microbiota and faecal metabolome in a static animal model of non-alcoholic steatohepatitis (NASH).

Design: This model was subjected to the following treatments: reverse osmosis water, AFO-202, N-163, AFO-202+N-163 and telmisartan treatment.

Benefits of Gut Microbiota Reconstitution by Beta 1,3-1,6 Glucans in Subjects with Autism Spectrum Disorder and Other Neurodegenerative Diseases.

Background: Aureobasidium pullulans (black yeast) AFO-202 strain-produced beta glucan, Nichi Glucan, has been shown to improve the behavior and sleep pattern along with an increase in α-synuclein and melatonin in children with autism spectrum disorder (ASD).

Objective: In this randomized pilot clinical study, we have evaluated the gut microbiota of subjects with ASD after consumption of Nichi Glucan.

Methods: Eighteen subjects with ASD were randomly allocated: six subjects in the control group (Group 1): conventional treatment comprising remedial behavioral therapies and L-carnosine 500 mg per day, and 12 subjects (Group 2) underwent supplementation with Nichi Glucan 0.

Independent Double-check of Infusion Pump Programming: An Anesthesia Improvement Effort to Reduce harm.

Introduction: Significant adverse drug events (ADEs) due to anesthesia infusion pump programming errors were reported at our institution. We incorporated independent two-provider infusion pump programming verification, an evidence-supported intervention, into our anesthesia medication infusion process with a goal of reducing associated ADEs to zero in 2 years.

Methods: Using the model for improvement, we developed key drivers and interventions and utilized plan-do-study-act (PDSA) cycles.

Improvement of sleep and melatonin in children with autism spectrum disorder after β-1,3/1,6-glucan consumption: An open-label prospective pilot clinical study.

Introduction: Poor sleep quality is a major problem in patients with autism spectrum disorder (ASD), and is attributed to low melatonin levels. Melatonin supplementation is recommended; however, its effectiveness varies. β-Glucans have previously been shown to improve melatonin levels in animal studies.

Beneficial Immune Regulation by Biological Response Modifier Glucans in COVID-19 and Their Envisaged Potentials in the Management of Sepsis.

Sepsis is a life-threatening condition caused by an abnormal immune response induced by infection with no approved or specific therapeutic options. We present our perspectives for the therapeutic management of sepsis through a four-way approach: (1) infection control through immune enhancement; (2) immune suppression during the initial hyper-inflammatory phase; (3) balanced immune-modulation to counter the later immune-paralysis phase; and (4) advantageous effects on metabolic and coagulation parameters throughout. COVID-19 is a virus-triggered, accelerated sepsis-like reaction that is associated with the rapid progress of an inflammatory cascade involving a cytokine storm and multiorgan failure.

Integrating the Synergy of the Gut Microbiome into Regenerative Medicine: Relevance to Neurological Disorders.

A new paradigm of cell therapy-based approaches as a solution to several diseases caused by damage or loss of cells/tissues leading to organ failure heralded the birth of a new branch in medicine called regenerative medicine (RM), which was further fueled by in vitro cell expansion and tissue engineering (TE) technologies, including the ability to grow embryonic stem cells, induce pluripotent stem cells, and so on. RM addresses organ failure by repair, regeneration, or restoration, rejuvenation using cells, stem cells, or progenitor cells as tools having added cell-derived products also as a tool, and extracellular matrix component-based support, either direct or indirect (e.g.

Improvement of behavioural pattern and alpha-synuclein levels in autism spectrum disorder after consumption of a beta-glucan food supplement in a randomised, parallel-group pilot clinical study.

Background: Autism spectrum disorders (ASDs) are a wide range of behavioural disabilities for which there are no definite interventional modalities available. Remedial therapies remain the only option but with varying outcomes. We have evaluated the Childhood Autism Rating Scale (CARS) and alpha-synuclein levels in this parallel-group, multiple-arm pilot clinical study after supplementation with a biological response modifier beta-glucan food supplement (Nichi Glucan).

Beneficial effects of novel aureobasidium pullulans strains produced beta-1,3-1,6 glucans on interleukin-6 and D-dimer levels in COVID-19 patients; results of a randomized multiple-arm pilot clinical study.

Objective: In this pilot clinical study, we report the beneficial effects of beta glucans derived from two strains AFO-202 and N-163 of a black yeast Aureobasidium pullulans on the biomarkers for cytokine storm and coagulopathy in COVID-19 patients.

Methods: A total of 24 RT-PCR positive COVID-19 patients were recruited and randomly divided into three groups (Gr): Gr. 1 control (n = 8) - Standard treatment; Gr.

β‑glucan vaccine adjuvant approach for cancer treatment through immune enhancement (B‑VACCIEN) in specific immunocompromised populations (Review).

The incidence of cancer, which is the second leading cause of mortality globally, continues to increase, although continued efforts are being made to identify effective treatments with fewer side‑effects. Previous studies have reported that chronic microinflammation, which occurs in diseases, including diabetes, along with weakened immune systems, may ultimately lead to cancer development. Chemotherapy, radiotherapy and surgery are the mainstream approaches to treatment; however, they all lead to immune system weakness, which in turn increases the metastatic spread.