Impact of Potentially Inappropriate Medications on Kidney Function in Chronic Kidney Disease: Retrospective Cohort Study

Introduction: Chronic kidney disease (CKD) represents a major public health burden. Potential inappropriate medications (PIMs) are common in patients with CKD. However, its impact on kidney outcomes has not been adequately elucidated for middle-aged patients. This study aimed to clarify the prescription status of PIMs for middle-aged patients with CKD and its effect on kidney function decline. Methods: Using an administrative claims database in Japan, a retrospective cohort study was conducted among Japanese patients with CKD (aged 20–74) who underwent annual health check-ups at least three times between April 2008 and December 2020. PIM exposure was defined as medications to be avoided in older adults as defined by the 2019 American Geriatrics Society Beers Criteria. The association between the number of prescribed PIMs and the decline in estimated glomerular filtration rate (eGFR) was examined using logistic regression models adjusted for clinical characteristics and laboratory variables. Results: A total of 43, 143 patients with CKD (mean age 57 years, median eGFR: 52 mL/min/1.73 m2) were analyzed, and approximately 40% of the patients were prescribed one or more PIMs. The most commonly prescribed PIMs were pain medications (18.5%), followed by gastrointestinal medications (9.8%), central nervous system medications (8.6%), and cardiovascular medications (8.6%). After adjustment, exposure to 2 or ≥3 PIMs was associated with an increased risk of 30% eGFR decline (adjusted odds ratio 1.71 [95% confidence interval, 1.24–2.37] and 1.65 [95% confidence interval, 1.08–2.52], respectively) as compared to the control group. Conclusion: This study showed that middle-aged patients with CKD who were prescribed ≥2 PIM had an increased risk of progression of CKD. Further studies are needed to analyze whether deprescribing steps contribute to reduce PIM prescriptions and prevent CKD progression

Maternal multivitamin intake and orofacial clefts in offspring: Japan Environment and Children's Study (JECS) cohort study

Objectives: Orofacial clefts are common birth defects with a lack of strong evidence regarding their association with maternal nutrition. We aimed to determine whether a relationship exists between maternal nutrient or multivitamin intake and orofacial clefts. Design: This is a prospective, population-based nationwide cohort study. Setting: The study was conducted in 15 regional centres, consisting of local administrative units and study areas. Participants: A total of 98 787 eligible mother–child pairs of the Japan Environment and Children’s Study were included. Intervention: Exposures were maternal nutrition and the use of supplemental multivitamins in mothers. Primary and secondary outcome measures: Outcomes were the occurrence of any orofacial cleft at birth. Multinomial logistic regression analyses were used to evaluate the association between maternal multivitamin intake and the incidence of orofacial clefts. Results: Of the 98 787 children, 69 (0.07%) were diagnosed with cleft lip alone, 113 (0.11%) were diagnosed with cleft lip and palate, and 52 (0.05%) were diagnosed with cleft palate within 1 month after birth. Regarding the total orofacial cleft outcome, statistically significant point estimates of relative risk ratios (RR) were determined for multivitamin intake before pregnancy (RR=1.71; 95% CI 1.06 to 2.77) and during the first trimester (RR=2.00; 95% CI 1.18 to 3.37), but the association was not significant for multivitamin intake after the first trimester (RR=1.34; 95% CI 0.59 to 3.01). Maternal micronutrient intake via food was not associated with the incidence of orofacial clefts in offspring. Conclusions: Intake of multivitamin supplements shortly before conception or during the first trimester of pregnancy was found to be associated with an increased incidence of orofacial clefts at birth. Pregnant women and those intending to become pregnant should be advised of the potential risks of multivitamin supplementation

Clinical epidemiology and pharmacoepidemiology studies with real-world databases

Hospital-based registry data, including patients’ information collected by academic societies or government based research groups, were previously used for clinical research in Japan. Now, real-world data routinely obtained in healthcare settings are being used in clinical epidemiology and pharmacoepidemiology. Real-world data include a database of claims originating from health insurance associations for reimbursement of medical fees, diagnosis procedure combinations databases for acute inpatient care in hospitals, a drug prescription database, and electronic medical records, including patients’ medical information obtained by doctors, derived from electronic records of hospitals. In the past ten years, much evidence of clinical epidemiology and pharmacoepidemiology studies using real-world data has been accumulated. The purpose of this review was to introduce clinical epidemiology and pharmacoepidemiology approaches and studies using real-world data in Japan

Association between maternal heavy metal exposure and Kawasaki Disease, the Japan Environment and Children’s Study (JECS)

妊婦の⾎中重⾦属濃度と⽣まれた子どもの川崎病発症との関連について 子どもの健康と環境に関する全国調査（エコチル調査）.京都大学プレスリリース. 2024-07-01.Kawasaki disease (KD) is an acute systemic vasculitis primarily affecting young children, with an unclear etiology. We investigated the link between maternal heavy metal exposure and KD incidence in children using the Japan Environment and Children’s Study, a large-scale nationwide prospective cohort with approximately 100, 000 mother–child pairs. Maternal blood samples collected during the second/third trimester were analyzed for heavy metals [mercury (Hg), cadmium (Cd), lead (Pb), selenium (Se), manganese (Mn)], divided into four quartiles based on concentration levels. KD incidence within the first year of life was tracked via questionnaire. Among 85, 378 mother–child pairs, 316 children (0.37%) under one year were diagnosed with KD. Compared with the lowest concentration group (Q1), the highest (Q4) showed odds ratios (95% confidence interval) for Hg, 1.29 (0.82–2.03); Cd, 0.99 (0.63–1.58); Pb, 0.84 (0.52–1.34); Se, 1.17 (0.70–1.94); Mn, 0.70 (0.44–1.11), indicating no concentration-dependent increase. Sensitivity analyses with logarithmic transformation and extended outcomes up to age 3 yielded similar results. No significant association was found between maternal heavy metal levels and KD incidence, suggesting that heavy metal exposure does not increase KD risk

In Situ Hybridization Analysis of the Expression of Futsch, Tau, and MESK2 Homologues in the Brain of the European Honeybee (Apis mellifera L.)

BACKGROUND: The importance of visual sense in Hymenopteran social behavior is suggested by the existence of a Hymenopteran insect-specific neural circuit related to visual processing and the fact that worker honeybee brain changes morphologically according to its foraging experience. To analyze molecular and neural bases that underlie the visual abilities of the honeybees, we used a cDNA microarray to search for gene(s) expressed in a neural cell-type preferential manner in a visual center of the honeybee brain, the optic lobes (OLs). METHODOLOGY/PRINCIPAL FINDINGS: Expression analysis of candidate genes using in situ hybridization revealed two genes expressed in a neural cell-type preferential manner in the OLs. One is a homologue of Drosophila futsch, which encodes a microtubule-associated protein and is preferentially expressed in the monopolar cells in the lamina of the OLs. The gene for another microtubule-associated protein, tau, which functionally overlaps with futsch, was also preferentially expressed in the monopolar cells, strongly suggesting the functional importance of these two microtubule-associated proteins in monopolar cells. The other gene encoded a homologue of Misexpression Suppressor of Dominant-negative Kinase Suppressor of Ras 2 (MESK2), which might activate Ras/MAPK-signaling in Drosophila. MESK2 was expressed preferentially in a subclass of neurons located in the ventral region between the lamina and medulla neuropil in the OLs, suggesting that this subclass is a novel OL neuron type characterized by MESK2-expression. These three genes exhibited similar expression patterns in the worker, drone, and queen brains, suggesting that they function similarly irrespective of the honeybee sex or caste. CONCLUSIONS: Here we identified genes that are expressed in a monopolar cell (Amfutsch and Amtau) or ventral medulla-preferential manner (AmMESK2) in insect OLs. These genes may aid in visualizing neurites of monopolar cells and ventral medulla cells, as well as in analyzing the function of these neurons

A three-component monooxygenase from Rhodococcus wratislaviensis may expand industrial applications of bacterial enzymes

地球外有機化合物に対する微生物代謝の解明から全く新規な酵素系を発見 --生命分子進化の理解や産業応用に期待--. 京都大学プレスリリース. 2021-01-20.The high-valent iron-oxo species formed in the non-heme diiron enzymes have high oxidative reactivity and catalyze difficult chemical reactions. Although the hydroxylation of inert methyl groups is an industrially promising reaction, utilizing non-heme diiron enzymes as such a biocatalyst has been difficult. Here we show a three-component monooxygenase system for the selective terminal hydroxylation of α-aminoisobutyric acid (Aib) into α-methyl-D-serine. It consists of the hydroxylase component, AibH1H2, and the electron transfer component. Aib hydroxylation is the initial step of Aib catabolism in Rhodococcus wratislaviensis C31-06, which has been fully elucidated through a proteome analysis. The crystal structure analysis revealed that AibH1H2 forms a heterotetramer of two amidohydrolase superfamily proteins, of which AibHm2 is a non-heme diiron protein and functions as a catalytic subunit. The Aib monooxygenase was demonstrated to be a promising biocatalyst that is suitable for bioprocesses in which the inert C–H bond in methyl groups need to be activated

Functional Sperm of the Yellowtail (Seriola quinqueradiata) Were Produced in the Small-Bodied Surrogate, Jack Mackerel (Trachurus japonicus).

Production of xenogeneic gametes from large-bodied, commercially important marine species in closely related smaller surrogates with short generation times may enable rapid domestication of the targeted species. In this study we aimed to produce gametes of Japanese yellowtail (Seriola quinqueradiata) using jack mackerel (Trachurus japonicus) as a surrogate with a smaller body size and shorter maturation period. Donor spermatogonia were collected from the testes of yellowtail males and transferred into the peritoneal cavity of 10- and 12-day-old jack mackerel larvae. Twenty days later, 59.5% of the recipients survived of which 88.2% had donor-derived germ cells in their gonads. One year later, genomic DNA templates were prepared from the semen of 96 male recipients and subjected to PCR analyses using primers specific for the yellowtail vasa sequence, resulting in the detection of positive signals in semen from two recipients. The milt collected from the recipients was used for fertilization with yellowtail eggs. Of eight hatchlings obtained from the crosses, two were confirmed to be derived from donor yellowtail by DNA markers, although the others were gynogenetic diploids. These findings indicate that it is possible to produce donor-derived sperm in xenogeneic recipients with smaller body size and shorter generation time by transplanting spermatogonia. Thus, the xenogeneic transplantation of spermatogonia might be a potential tool to produce gametes of large-bodied, commercially important fish although the efficiency of the method requires further improvement. This is the first report demonstrating that donor-derived sperm could be produced in xenogeneic recipient via spermatogonial transplantation in carangid fishes

Preserving the C7 spinous process in laminectomy combined with lateral mass screw to prevent axial symptom

AbstractBackgroundPreserving the C7 spinous process during cervical laminoplasty has been reported to prevent axial symptom. Some patients underwent laminectomy and fixation developed the symptom. The objective of this article was to investigate whether axial symptom can be reduced by preserving the C7 spinous process during cervical laminectomy and fixation with lateral mass screw.MethodsBetween 2005 and 2008, data of 53 patients who underwent laminectomy and lateral mass-screw fixation for multilevel cervical myelopathy were reviewed. Analysis consisted of the incidence of axial symptom, Japan Orthopaedic Association (JOA) scores, recovery rate, cervical lordotic angle, and atrophy rate of cervical posterior muscle. Axial symptom severity was quantified by a visual analog scale (VAS). Twenty-five patients were decompressed from C3 to C7 (group A) and 28 from C3 to C6 with dome-shape removal of the C7 superior lamina (group B).ResultsAnalysis of final follow-up data showed improvement in clinical outcome for both groups. No difference in recovery rate, cervical lordotic angle and atrophy rate was observed between groups. Postoperative axial-neck pain was significantly rarer in group B than in group A. Axial symptom severity was correlated with cervical posterior muscle atrophy rate; correlation coefficient was 0.665.ConclusionThe C7 spinous process might play an important role in preventing axial symptom, but there is a need for randomized, control studies with long-term follow-up to clarify the results