Non-cancer-related Deaths in Cancer Survivors: A Nationwide Population-Based Study in Japan.

BACKGROUND: Advancements in cancer care have improved survivorship, potentially leading to changes in mortality causes. This study aimed to investigate the causes of death among cancer survivors, specially focusing on non-cancer-related mortality. METHODS: This nationwide population-based cohort study analyzed the causes of death based on the time since cancer diagnosis using data from the National Cancer Registry in Japan between January 2016 and December 2019. Non-cancer-related deaths were identified, and mortality risks associated with non-cancer diseases were compared to those of the Japanese general population using standardized mortality ratios (SMRs) with 95% confidence intervals (CIs). Follow-up period was up to 4 years after cancer diagnosis. RESULTS: A total of 3,990,661 patients (45.8%, women) were included in the analysis, yielding 6,237,269 person-years of follow-up. Of these, 1,001,857 (25.1%) patients died during the study period. Cancer-related and non-cancer-related causes accounted for 86.6% and 13.4% of deaths, respectively. The proportion of non-cancer-related deaths increased from 10.2% at 6 months to 31.6% at 4 years after cancer diagnosis. Heart disease (21.8%), cerebrovascular disease (9.8%), and pneumonia (9.1%) were the leading cause of non-cancer-related deaths: The SMRs for these diseases were 2.69 (95% CI, 2.66-2.72), 2.07 (95% CI, 2.03-2.10), and 2.41 (95% CI, 2.36-2.45), respectively. The SMR for suicide was 1.81 (95% CI, 1.74-1.89); however, it lost significance in males and females 2 and 2.5 years after cancer diagnosis, respectively. CONCLUSIONS: The proportion of non-cancer-related deaths among cancer patients has increased over time, emphasizing the need to manage cancer and its comorbidities carefully.

An MFN2-related Charcot-Marie-Tooth Disease Patient with Optic Nerve Atrophy, Neurogenic Bladder Dysfunction, and Diaphragmatic Weakness.

Charcot-Marie-Tooth disease (CMT) is a common hereditary peripheral polyneuropathy encompassing distinct monogenetic disorders. Pathogenic mutations in mitofusin 2 (MFN2) are the most frequent cause of its axonal type, CMT type 2A, with diverse phenotypes. We herein report a Japanese patient with a novel heterozygous MFN2 pathogenic variant (c.740 G>C, p.R247P) and severe CMT phenotypes, including progressive muscle weakness, optic atrophy, urinary inconsistency, and restrictive pulmonary dysfunction with eventration of the diaphragm that developed over her 60-year disease course. Our case expands the clinico-genetic features of MFN2-related CMT and highlights the need to evaluate infrequent manifestations during long-term care of CMT patients.

Additional betalain accumulation by genetic engineering leads to a novel flower color in lisianthus (Eustoma grandiflorum).

Betalains, comprising violet betacyanins and yellow betaxanthins, are pigments found in plants belonging to the order Caryophyllales. In this study, we induced the accumulation of betalains in ornamental lisianthus (Eustoma grandiflorum) by genetic engineering. Three betalain biosynthetic genes encoding CYP76AD1, dihydroxyphenylalanine (DOPA) 4,5-dioxygenase (DOD), and cyclo-DOPA 5-O-glucosyltransferase (5GT) were expressed under the control of the cauliflower mosaic virus (CaMV) 35S promoter in lisianthus, in which anthocyanin pigments are responsible for the pink flower color. During the selection process on hygromycin-containing media, some shoots with red leaves were obtained. However, most red-colored shoots were suppressed root induction and incapable of further growth. Only clone #1 successfully acclimatized and bloomed, producing pinkish-red flowers, with a slightly greater intensity of red color than that in wild-type flowers. T1 plants derived from clone #1 segregated into five typical flower color phenotypes: wine red, bright pink, pale pink, pale yellow, and salmon pink. Among these, line #1-1 showed high expression levels of all three transgenes and exhibited a novel wine-red flower color. In the flower petals of line #1-1, abundant betacyanins and low-level betaxanthins were coexistent with anthocyanins. In other lines, differences in the relative accumulation of betalain and anthocyanin pigments resulted in flower color variations, as described above. Thus, this study is the first to successfully produce novel flower color varieties in ornamental plants by controlling betalain accumulation through genetic engineering.

Herpes gestationis in a mother and newborn: immunoclinical perspectives based on a weekly follow-up of the enzyme-linked immunosorbent assay index of a bullous pemphigoid antigen noncollagenous domain.

BACKGROUND: Herpes gestationis (HG) is a rare, autoimmune, bullous disease that occurs during the second or third trimester and usually resolves over weeks or months after delivery. Neonates with HG are rare (estimated at 1 per 100,000 cases). Although anti-180-kDa bullous pemphigoid (BP180) autoantibody and transfer of this autoantibody are known as the cause, to our knowledge, no coordinated analysis of clinical symptoms and anti-BP180 antibody enzyme-linked immunosorbent assay titers has been reported in a mother and neonate with HG. OBSERVATIONS: We describe a 33-year-old woman with HG and her neonate with vesicular erythematous lesions and the weekly follow-up results of the BP180 noncollagenous domain (NC16a) enzyme-linked immunosorbent assay. CONCLUSIONS: Almost the same titer of pathogenic antibody as that in the mother is transferred to the neonate. The plasma elimination half-life of anti-BP180 antibody is approximately 15 days in mother and neonate. An abrupt twin peak increase in the BP180 enzyme-linked immunosorbent assay index from maternal serum was observed just before and after delivery, possibly explaining why HG usually occurs in the last trimester of pregnancy and exacerbates postpartum. Lesions in the neonate resolve without treatment far before pathogenic antibody disappears, suggesting that factors other than anti-BP180 antibodies may be involved in the generation of eruptions. Frequent testing of the BP180 enzyme-linked immunosorbent assay greatly facilitates therapeutic planning.

Preparation of recombinant rat eosinophil-associated ribonuclease-1 and -2 and analysis of their biological activities.

Rat eosinophils contain eosinophil-associated ribonucleases (Ears) in their granules. Ears are thought to be synthesized as pre-forms and stored in the granules as mature forms. However, the N-terminal amino acid of mature Ear-1 and Ear-2 is still controversial. Therefore, we prepared two recombinant mature forms of Ear-1 and Ear-2 in which the N-terminal amino acids are Ser24 (S) [Ear-1 (S) and Ear-2 (S)] and Gln26 (Q) [Ear-1 (Q) and Ear-2 (Q)], and analyzed their biological activities by comparing them with those of pre-form Ear-1 and pre-form Ear-2. The four mature Ears showed RNase A activity as well as bovine pancreatic RNase A activity, but pre-Ear-1 and pre-Ear-2 showed no RNase A activity. Mature Ear-1 (Q) and mature Ear-2 (Q) showed more potent RNase A activity than mature Ear-1 (S) and mature Ear-2 (S), respectively. The RNase A activities of mature Ear-1 (Q) and mature Ear-2 (Q) were reduced by treatment at 96 degrees C for 20 min or with RNase inhibitor. The growth of Escherichia coli was inhibited by both pre-Ears and mature Ears in a concentration-dependent manner, and was almost completely suppressed at 1.0 microM. The bactericidal activities of mature Ear-1 (Q) and mature Ear-2 (Q) were not inhibited by RNase inhibitor, but was increased by treatment at 96 degrees C for 20 min.