Miwa Hospital

Abstract Background L-DOPA remains the cornerstone of Parkinson’s disease (PD) therapy, yet its long-term metabolic consequences are poorly understood. Folate deficiency appears disproportionately frequent in patients with dementia with Lewy bodies (DLB), a synucleinopathy closely related to PD. We hypothesized that folate deficiency is more prevalent in DLB than in Alzheimer’s disease (AD) or cognitively normal controls (NC), possibly due to excessive folate consumption during L-DOPA metabolism, which may elevate homocysteine levels and increase vascular risk. Methods We conducted a retrospective cross-sectional study comparing serum folate levels among DLB (n = 15), AD (n = 73), and NC (n = 7). Deficiency rates for folate, vitamin B12 (B12), and vitamin B1 (B1) were compared using Fisher’s exact test. Within DLB, associations) between folate/B12 deficiency and L-DOPA usage were assessed. Scatter plots visualized relationships between daily L-DOPA dosage and serum folate or B12 levels. Macrocytosis (MCV >100 fL) was evaluated as a potential indicator of vitamin depletion. Results Folate deficiency was significantly more prevalent in DLB than in AD or NC (p = 0.0021). Within DLB, folate deficiency was more frequent among L-DOPA users (p = 0.0406), while B12 deficiency showed no significant association. B12 levels varied widely, with some patients showing elevated concentrations. In contrast, folate levels tended to fall below the reference limit in all but one L-DOPA user. MCV was not a reliable indicator of deficiency. Conclusion L-DOPA–treated DLB patients may require individualized monitoring and tailored supplementation to mitigate vascular risk.

ABSTRACTExosomal microRNAs (miRNAs) are candidates for liquid biopsies. Organoid culture systems enable long‐term expansion of the colon epithelium. This study evaluated exosomal miRNAs from colorectal cancer organoids for liquid biopsy. Organoids were established from normal colon and colorectal cancer tissues. Exosomes were isolated from conditioned media. miRNAs were extracted from exosomes and compared using microarray analysis. Exosomal miRNAs expression levels in the sera of healthy patients and patients with colorectal cancer were compared at a single institution. The multicenter study was validated using miRNAs upregulated in the serum of colorectal cancer patients, along with exosomal miRNAs reported to be upregulated in colorectal adenoma organoids and sera. A total of 44 exosomal miRNAs were commonly expressed in both normal colorectal epithelial cells and colorectal cancer organoids, whereas 59 were exclusively expressed in colorectal cancer organoids. In a single‐center cohort study, two exosomal miRNAs (miR‐4284 and miR‐5100) were upregulated in the serum of colorectal cancer patients. In a multicenter study, four exosomal miRNAs (miR‐4284, miR‐5100, miR‐1246, and miR‐1290) were upregulated in the serum of patients with colorectal cancer. The combination of these four exosomal miRNAs had comparable diagnostic performance to carcinoembryonic antigen, with an area under the curve of 0.75 (95% confidence interval: 0.65–0.83) versus 0.79 (95% confidence interval: 0.70–0.87). Combining the four miRNAs with carcinoembryonic antigen improved diagnostic accuracy, with an area under the curve of 0.82 (95% confidence interval: 0.74–0.89). Exosomal miRNAs derived from colorectal cancer organoids can serve as diagnostic biomarkers for colorectal cancer.

The temporal bone petrosa is connected to the occipital bone at two sites: one junction with the basilar part (medial junction) and another with the lateral part (lateral junction). Using histological specimens from 45 human fetuses (approximately 7–39 weeks of gestational age or GA), we aimed to describe possible changes in histology and topographical anatomy during processes toward the ossified union. In the early term, the junctions were characterized by dense mesh‐like fibers that likely corresponded to the thickened basal laminae of the composite cartilage cells. Notably, the mesh‐like structure disappeared until 12 weeks of GA and, irrespective of whether a remnant fibrous tissue was present or absent, cartilage tissues became continuous between the occipital and petrosal sides. Until 25 weeks of GA, the inferolateral marginal part of the spheno‐occipital junction cartilage extended to the medial junction and attached to the ossified petrosa. The medial junction sometimes contained an irregularly shaped cartilage mass or a woven bone with bone trabeculae, but it was usually attached directly to the bony petrosa without any interruption by calcified cells. In contrast, at the late‐term lateral junction, a cartilage mass was sandwiched by bipolar ossification centers on the temporal and occipital bone sides. As the endochondral ossification advances, bones at and around the lateral junction seemed to grow and cover the expanding mastoid air cells. However, the fetal medial junction might grow, in accordance with midline growth at the spheno‐occipital junction cartilage. Alternatively, the bony union of these two junctions might establish postnatally.

The primary goal in treating patients with breast cancer who have positive axillary lymph nodes is to achieve optimal tumor control while minimizing side effects that include breast cancer-related lymphedema (BCRL) [...].