Kyushu University of Health and Welfare (九州保健福祉大学, Kyūshū hoken fukushi daigaku) is a private university in Nobeoka, Miyazaki, Japan, established in 1999..
OBJECTIVE:The ultimate goal of perinatal care is to ensure that infants survive without neurological impairment. Despite advances in medical technology and healthcare systems that have markedly decreased perinatal mortality, cerebral palsy has shown only a gradual decline in recent population-based studies. The aim of this study was to use a pathway classification system to analyze brain injury cases detected at or beyond 35 weeks' gestation and to clarify temporal changes in the incidence and causal pathways of intrapartum brain injury and its contributing factors in Miyazaki Prefecture, Japan. METHODS:Of 151,558 births recorded in Miyazaki Prefecture from 2001 to 2015, 303 cases of brain injury were registered in the regional perinatal case-review system. Of these, 134 were detected at ≥35 weeks. Brain injury was categorized as congenital anomalies, antepartum, intrapartum, or neonatal onset. Each case was further classified using a pathway system that considered distal and proximal risk factors. Temporal trend analysis was performed across three consecutive 5-year intervals (2001-2005, 2006-2010, and 2011-2015). RESULTS:Of the 134 cases, 25% were classified as intrapartum-related, 23% as antepartum-related, and 5% as neonatal-related. Overall, the incidence of brain injury at ≥35 weeks decreased significantly over time. Significant downward trends were observed in total cases and intrapartum-related brain injury, with the reduction in intrapartum cases being especially pronounced. Antepartum-related brain injury declined more gradually. Further analysis revealed that the incidence of hypoxia-related intrapartum brain injuries decreased over time, whereas bacterial infection-related intrapartum cases were observed only in the earliest epoch. CONCLUSIONS:This population-based study identified temporal changes in perinatal brain injury detected at or beyond 35 weeks' gestation over 15 years. The incidence of perinatal brain injury declined significantly, particularly intrapartum-related cases with hypoxia-related injury. These improvements might reflect advances in regionalized perinatal care, the establishment of perinatal centers, or multidisciplinary education and training. Further efforts to optimize intrapartum assessment and management would contribute to continued reductions in severe perinatal brain injury.
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. IGF-1, Dystrophin, CD44 and MYH3 in diaphragm, plasma and skeletal muscle were evaluated by ELISA and immunohistochemistry. Mean IGF-1 expression was 20.32% and 16.27% higher in plasma (p = 0.03) and diaphragm respectively in Neu-REFIX group. Mean dystrophin was higher in Neu-REFIX group by 70.3% and 4.7% in diaphragm and plasma respectively than control. H-score intensity of CD44 + was > 2.0 with an MYH3-positivity 20% higher in Neu-REFIX than control. Oral administration of Neu REFIX was safe. Significantly enhanced plasma IGF-1 beside increased Dystrophin, MYH3 and CD44, proving a restoration of muscle regeneration and differentiation, especially in diaphragm, makes us recommend it as a disease modifying adjuvant in both early and advanced stages of DMD.
Objective Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder that leads to increasing muscle weakening and early death. Steroids, the standard treatment of choice in slowing down disease progression, are plagued with adverse effects. Anti-inflammatory, antifibrotic effects and enhancement of muscle regeneration biomarkers after oral consumption of Aureobasidium pullulans strain N-163-produced beta 1,3–1,6-glucan (Neu REFIX) having been demonstrated in clinical and preclinical studies of DMD; in this study, we have investigated the effects on the gut microbiome in patients with DMD.Design Twenty-seven patients with DMD were included in the study (control (n=9), N-163 (n=18)). Whole-genome metagenomic sequencing was performed in pre-N-163 and post-N-163 intervention faecal samples of each of these participants.Results After N-163 beta-glucan administration, the constitution of the gut microbiome in all the participants was modified to one with positive outcomes on health. There was an increase in butyrate-producing species such as Roseburia and Faecalibacterium prausnitzii. There was a decrease in harmful bacteria associated with inflammation such as enterobacteria and Alistipes.Conclusion Beneficial reconstitution of the gut microbiome after Neu REFIX beta-glucan administration and its safety have been confirmed. These outcomes correlating with the anti-inflammatory, anti-fibrotic effects along with increase in dystrophin in skeletal muscle and plasma, reported earlier make us recommend further in-depth exploration on its role in epigenetic manipulation which when found encouraging might help other genetic diseases as well.Trial registration number CTRI/2021/05/033346.
Background:Several biomarkers, including C-reactive protein (CRP), ferritin, D-dimer, and Interleukin-6 (IL-6), are established predictors of disease severity and respiratory failure in patients with COVID-19. Objective:In this randomised clinical study, we evaluated the efficiency of the combination of 2 variants' AFO-202 and N-163 strains of Aureobasidium pullulans produced 1,3-1,6 β-glucans in comparison with the control arm on these biomarkers in COVID-19 patients. Methods:Forty RT-PCR positive COVID-19 patients were divided into 2 groups: control (n = 22) and standard treatment; ii. (n = 18) - Standard treatment + combination of AFO-202 and N-163 beta glucans for 15 days. Results:IL-6 levels significantly decreased in the treatment group on day 7 (P = 0.03) but not by day 15 (P = 0.30). CRP levels in the treatment group decreased at day 7 (5.53 ± 8.21 mg/L) compared to baseline but showed no significant difference from the control group (4.91 ± 12.54 mg/L, P = 0.98). At day 15, CRP levels remained lower in the treatment group (5.42 ± 10.41 mg/L) but increased in the control group (14.0 ± 37.16 mg/L), with no significant difference (P = 0.52). Ferritin levels dropped significantly in the treatment group by day 15 (from 560.58 ± 537.30 ng/mL to 127.51 ± 215.91 ng/mL) but increased in the control (P = 0.98). D-dimer levels decreased in the treatment group by day 15 but were not significantly different from controls (P = 0.56). Conclusion:These results indicate that while co-supplementation with AFO-202 and N-163 beta-glucans led to improvement in CRP, ferritin, and IL-6 levels in COVID-19 patients, only the reduction in IL-6 levels on day 7 reached statistical significance. Further long-term multicentric clinical research is warranted to validate the potential of these supplements as treatment adjuncts, for addressing inflammation in COVID-19, especially in vulnerable populations infected with emerging SARS-CoV-2 variants.
Herein, we investigated the role of an essential transcription factor in the human T-cell leukemia virus type 1 (HTLV-1) provirus, the HTLV-1 basic zip factor (HBZ), in HTLV-1 infections and adult T-cell leukemia/lymphoma (ATL). We designed five synthetic guide RNAs (sgRNAs) targeting HBZ and introduced them into ATL and HTLV-1 infected cell lines using clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9). Of all sgRNAs, sgRNA 171 was the most efficient in introducing mutations at the target site as 70–80% of Cas9/sgRNA 171-transfected host cells contained mutations. Various types of mutations, including deletions, substitutions, insertion, and combinations, were detected in the Cas9/sgRNA 171-treated cells. Based on the predicted peptide sequence, most mutant clones were assumed to inactivate the HBZ mRNA. The mRNA levels of the transactivator from the X-gene region (tax) increased after HBZ editing by Cas9/sgRNA 171. No off-target effects were observed in the four human genome regions partially homologous to the sgRNA 171 target sequence. Furthermore, ST-1 cells transfected with Cas9/sgRNA 171 displayed significantly reduced proliferation. These findings suggest that the HBZ mRNA might be crucial for the survival of HTLV-1-infected cells, including ATL, providing insights into the molecular pathogenesis of the HTLV-1 provirus.
