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Background PRDM12 polyalanine tract expansions cause two different disorders: midfacial toddler excoriation syndrome (MiTES; itch with normal pain sensation associated with 18 homozygous alanines (18A); and congenital insensitivity to pain (CIP) with normal itch associated with 19 homozygous alanines (19A). Knowledge of the phenotype, genotype and disease mechanism of MiTES is incomplete. Why 18A vs. 19A PRDM12 can cause almost opposite phenotypes is unknown; no other polyalanine or polyglutamine tract expansion disease causes two such disparate phenotypes. Objectives To assess the genotype and phenotype of nine new, nine atypical and six previously reported patients diagnosed with MiTES. Methods Using cell lines with homozygous PR domain zinc finger protein 12 (PRDM12) containing 12 alanines (12A; normal), 18A (MiTES) and 19A (CIP), we examined PRDM12 aggregation and subcellular localization by image-separation confocal microscopy and subcellular fractionation Western blotting. Results MiTES presents in the first year of life; in all cases the condition regresses over the first decade, leaving scarring. The MiTES phenotype is highly distinctive. Features overlapping with PRDM12 CIP are rarely found. The genotype–phenotype study of the PRDM12 polyalanine tract shows that having 7–15 alanines is normal; 16–18 alanines is associated with MiTES; 19 alanines leads to CIP; and no clinically atypical cases of MiTES had a polyalanine tract expansion. PRDM12 aggregation and subcellular localization differed significantly between 18A and normal 12A cell lines and between 18A and 19A cell lines. MiTES is a new protein-aggregation disease. Conclusions We provide diagnostic criteria for MiTES and improved longitudinal data. MiTES and CIP are distinct phenotypes, despite their genotypes varying by a single alanine in the PRDM12 polyalanine tract. We found clear distinctions between the cellular phenotypes of normal, MiTES and CIP cells. We hypothesize that the developmental environment of the trigeminal ganglion is unique and critically sensitive to pre- and postnatal levels of PRDM12. [ABSTRACT FROM AUTHOR]

Background Complex regional pain syndrome type 1 (CRPS-1) is a rare, disabling and sometimes chronic disorder usually arising after a trauma. This exploratory study examined whether patients with chronic CRPS-1 have a different genetic profile compared with those who do not have the condition. Methods Exome sequencing was performed to seek altered non-synonymous SNP allele frequencies in a discovery cohort of well-characterised patients with chronic CRPS-1 (n=34) compared with population databases. Identified SNP alleles were confirmed by Sanger sequencing and sought in a replication cohort (n=50). Gene expression of peripheral blood macrophages was assessed. Results In the discovery cohort, the rare allele frequencies of four non-synonymous SNPs were statistically increased. The replication cohort confirmed this finding. In a chronic pain cohort, these alleles were not overexpressed. In total, 25 out of 84 (29.8%) patients with CRPS-1 expressed a rare allele. The SNPs were rs41289586 in ANO10, rs28360457 in P2RX7, rs1 126930 in PRKAG1 and rs80308281 in SLC12A9. Males were more likely than females to have a rare SNP allele, 8 out of 14 (57.1%) vs 17 out of 70 (24.3%) (Fisher's p=0.023). ANO10, P2RX7, PRKAG1 and SLC12A9 were all expressed in macrophages from healthy human controls. Conclusion A single SNP in each of the genes ANO10, P2RX7, PRKAG1 and SLC12A9 was associated with developing chronic CRPS-1, with more males than females expressing these rare alleles. Our work suggests the possibility that a permissive genetic background is an important factor in the development of CRPS-1. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to provide new insights into the potential of oyster mushroom ( Pleurotus ostreatus ) ethanolic extract in preventing obesity through the inhibition of Pparg expression and modulation of methylation level on Pparg promoter during 3T3-L1 adipocyte differentiation., Methods: This in vitro quantitative experimental study was conducted by treating the 3T3-L1 cell line differentiated using 0.5 mM methyl-isobutyl-xanthine, 1 μM dexamethasone, and 10 μg/mL insulin-containing medium with oyster mushroom ethanolic extract. The extract was obtained from 80 g of dried oyster mushroom powder extracted three times with 800 mL of ethanol, filtered, evaporated, and reconstituted in dimethyl sulfoxide (DMSO) to final concentrations of 0, 25, 50, and 100 µg/mL, with DMSO limited to 0.5% in all solutions. Pparg mRNA expression was quantified by qRT-PCR analysis and Pparg promoter methylation levels were measured quantitatively by pyrosequencing of bisulfite-treated DNA samples., Results: The addition of 25 µg/mL oyster mushroom ethanolic extract significantly suppressed Pparg mRNA expression with no significant change in the Pparg promoter methylation levels., Conclusion: Oyster mushroom ethanolic extract inhibited Pparg mRNA expression without altering Pparg promoter methylation, suggesting reduced adipocyte differentiation. This study emphasizes the potential of oyster mushroom in the prevention or treatment of obesity by inhibiting adipocyte differentiation., Competing Interests: The authors report no conflicts of interest in this work., (© 2025 Ariyanto et al.)

Background/aims: Colonoscopy is widely used as a diagnostic and preventive procedure for colorectal diseases. The most recent guidelines advocate the use of a low-residue diet (LRD) for bowel preparation before colonoscopy. LRD duration varies considerably, with recommended 1-day and multiple-day regimens in clinical practice., Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched multiple databases for randomized controlled trials (RCTs) and analyzed the outcomes using a fixed-effects model., Results: Six RCTs with 2,469 subjects were included in this study. The rates of adequate bowel preparation for 1-day and >1-day were 87.2% and 87.1%, respectively. No statistically significant differences were observed between the 1-day and >1-day LRD in adequate bowel preparation (odds ratio [OR], 1.03; 95% confidence interval [CI], 0.76-1.41; p=0.84; I2=0%), polyp detection rate (OR, 0.91; 95% CI, 0.76-1.09; p=0.29; I2=16%), adenoma detection rate (OR, 0.87; 95% CI, 0.71-1.08; p=0.21; I2=0%), and withdrawal time (mean difference, -0.01; 95% CI, -0.25 to 0.24; p=0.97; I2=63%)., Conclusions: The efficacy of 1-day and multiple-day LRD is comparable in achieving satisfactory bowel preparation, highlighting their similar impact on the detection of polyps and adenomas during colonoscopy.