Effects of consecutive bed bathing with weak versus ordinary pressure on skin barrier recovery of hospitalised older adults: A within-person randomised controlled trial.

AIM: Wiping pressure (WP [mmHg]) during bed baths is essential to maintain skin integrity and care quality for older adults. However, effects of different wiping pressures on skin barrier recovery over multiple days remain unclear. This study evaluated and compared the effects of consecutive bed bathing with weak pressure and that with ordinary pressure on skin barrier recovery of hospitalised older adults. METHODS: This within-person, randomised, controlled trial involved 254 forearms (127 patients) and was conducted at a general hospital. Forearms were blinded and randomly assigned a site and sequence of two bed bathing sessions: wiping three times with weak (10≤WP<20) and ordinary pressure (20≤WP<30) once per day for 2 consecutive days. The skin barrier was assessed daily based on transepidermal water loss (TEWL) and stratum corneum hydration (SCH) before and 15 min after the interventions. Dry skin was assessed using the overall dry skin score. RESULTS: A linear mixed model showed that the time courses of TEWL and SCH differed significantly between groups. Impaired skin barrier function caused by ordinary pressure on the first day did not recover to baseline values the next day, whereas weak pressure did not cause significant changes. During subgroup analyses, TEWL of patients with dry skin was more likely to increase with ordinary pressure. CONCLUSIONS: Despite decreased skin barrier recovery experienced by older adults, our findings suggest the safety of weak pressure and highlight the importance of WP during bed baths. Weak pressure is particularly desirable for patients with dry skin. TRIAL REGISTRATION: UMIN000048838.

RBM24 promotes U1 snRNP recognition of the mutated 5' splice site in the IKBKAP gene of familial dysautonomia.

The 5' splice site mutation (IVS20+6T>C) of the inhibitor of κ light polypeptide gene enhancer in B cells, kinase complex-associated protein (IKBKAP) gene in familial dysautonomia (FD) is at the sixth intronic nucleotide of the 5' splice site. It is known to weaken U1 snRNP recognition and result in an aberrantly spliced mRNA product in neuronal tissue, but normally spliced mRNA in other tissues. Aberrantly spliced IKBKAP mRNA abrogates IKK complex-associated protein (IKAP)/elongator protein 1 (ELP1) expression and results in a defect of neuronal cell development in FD. To elucidate the tissue-dependent regulatory mechanism, we screened an expression library of major RNA-binding proteins (RBPs) with our mammalian dual-color splicing reporter system and identified RBM24 as a regulator. RBM24 functioned as a cryptic intronic splicing enhancer binding to an element (IVS20+13-29) downstream from the intronic 5' splice site mutation in the IKBKAP gene and promoted U1 snRNP recognition only to the mutated 5' splice site (and not the wild-type 5' splice site). Our results show that tissue-specific expression of RBM24 can explain the neuron-specific aberrant splicing of IKBKAP exon 20 in familial dysautonomia, and that ectopic expression of RBM24 in neuronal tissue could be a novel therapeutic target of the disease.

Rectifier of aberrant mRNA splicing recovers tRNA modification in familial dysautonomia.

Familial dysautonomia (FD), a hereditary sensory and autonomic neuropathy, is caused by missplicing of exon 20, resulting from an intronic mutation in the inhibitor of kappa light polypeptide gene enhancer in B cells, kinase complex-associated protein (IKBKAP) gene encoding IKK complex-associated protein (IKAP)/elongator protein 1 (ELP1). A newly established splicing reporter assay allowed us to visualize pathogenic splicing in cells and to screen small chemicals for the ability to correct the aberrant splicing of IKBKAP. Using this splicing reporter, we screened our chemical libraries and identified a compound, rectifier of aberrant splicing (RECTAS), that rectifies the aberrant IKBKAP splicing in cells from patients with FD. Here, we found that the levels of modified uridine at the wobble position in cytoplasmic tRNAs are reduced in cells from patients with FD and that treatment with RECTAS increases the expression of IKAP and recovers the tRNA modifications. These findings suggest that the missplicing of IKBKAP results in reduced tRNA modifications in patients with FD and that RECTAS is a promising therapeutic drug candidate for FD.

Highly Efficient Fluorescent Probe to Visualize Protein Interactions at the Superresolution.

Superresolution microscopy (SR microscopy) of protein-protein interactions (PPIs) occurring in subcellular structures is essential for understanding cellular functions. However, a powerful and useful technology for SR microscopy of PPIs remains elusive. Here, we develop a highly efficient photoconvertible fluorescent probe, named split-Dendra2, for SR microscopy of PPIs in the cell. We found that split-Dendra2 enables a highly efficient detection of PPIs, making it possible to perform SR microscopy of PPIs with high spatial resolution and high image reconstruction fidelity. We demonstrate the utility of split-Dendra2 by visualizing PPIs occurring in small subcellular structures at the superresolution, such as clathrin-coated pits and focal adhesions, which cannot be visualized by the existing tools. Split-Dendra2 offers a powerful and useful tool that greatly expands the possibility of SR microscopy and can contribute to revealing the function of PPIs at the nanoscale resolution.

Improved hourly estimate of aerosol optical thickness over Asian land by fusing geostationary satellites Fengyun-4B and Himawari-9.

Asian over-land aerosols are complexities due to a mixture of anthropogenic air pollutants and natural dust. The accuracy of the aerosol optical thickness (AOT) retrieved from the satellite is crucial to their application in the aerosol data assimilation system. Fusion of AOTs with high spatiotemporal resolution from next-generation geostationary satellites such as Fengyun-4B (FY-4B) and Himawari-9, provides a new high-quality dataset capturing the aerosol spatiotemporal variability for data assimilation. This study develops a complete fusion algorithm to estimate the optimal AOT over-land in Asia from September 2022 to August 2023 at 10 km × 10 km resolution with high efficiency. The data fusion involves four steps: (1) investigating the spatiotemporal variability of FY-4B AOT within the past 1 h and 12 km radius calculation domain; (2) utilizing the aerosol spatiotemporal variability characteristics to estimate FY-4B pure and hourly merged AOTs; (3) performing bias corrections for FY-4B and Himwari-9 hourly merged AOT for different observation times and seasons considering pixel-level errors for each satellite; (4) fusing the bias-corrected FY-4B and Himawari-9 hourly merged AOT based on maximum-likelihood estimation (MLE) method. Compared to the original FY-4B AOT, validation with AERONET observation confirms that the root mean square error (RMSE) of hourly merged FY-4B AOT decreases by around 40.6 % and the correlation coefficient (CORR) increases by about 27.8 %. Compared to FY-4B and Himawari-9 merged AOT, the fused AOT significantly decreases (increases) RMSE (CORR) by around 24.7 % (7.3 %) and 20.2 % (5.6 %). In addition, fused AOT is double the number of single-sensor merged AOT. Fusion aerosol map accurately describes the spatial and temporal variations in Asian regions controlled by air pollution and dust storms. Further studies are required for other landscapes with different satellite combinations to promote the application in the data assimilation system.

Evaluation and uncertainty analysis of Himawari-8 hourly aerosol product version 3.1 and its influence on surface solar radiation before and during the COVID-19 outbreak.

The hourly Himawari-8 version 3.1 (V31) aerosol product has been released and incorporates an updated Level 2 algorithm that uses forecast data as an a priori estimate. However, there has not been a thorough evaluation of V31 data across a full-disk scan, and V31 has yet to be applied in the analysis of its influence on surface solar radiation (SSR). This study firstly investigates the accuracy of V31 aerosol products, which includes three categories of aerosol optical depth (AOD) (AODMean, AODPure, and AODMerged) as well as the corresponding Ångström exponent (AE), using ground-based measurements from the AERONET and SKYNET. Results indicate that V31 AOD products are more consistent with ground-based measurements compared to previous products (V30). The highest correlation and lowest error were seen in the AODMerged, with a correlation coefficient of 0.8335 and minimal root mean square error of 0.1919. In contrast, the AEMerged shows a larger discrepancy with measurements unlike the AEMean and AEPure. Error analysis reveals that V31 AODMerged has generally stable accuracy across various ground types and geometrical observation angles, however, there are higher uncertainties in areas with high aerosol loading, particularly for fine aerosols. The temporal analysis shows that V31 AODMerged performs better compared to V30, particularly in the afternoon. Finally, the impacts of aerosols on SSR based on the V31 AODMerged are investigated through the development of a sophisticated SSR estimation algorithm in the clear sky. Results demonstrate that the estimated SSR is significant consistency with those of well-known CERES products, with preservation of 20 times higher spatial resolution. The spatial analysis reveals a significant reduction of AOD in the North China Plain before and during the COVID-19 outbreak, resulting in an average 24.57 W m-2 variation of the surface shortwave radiative forcing in clear sky daytime.

Concise synthesis of the anti-HIV nucleoside EFdA.

EFdA (4'-ethynyl-2-fluoro-2'-deoxyadenosine), a nucleoside reverse transcriptase inhibitor with extremely potent anti-HIV activity, was concisely synthesized from (R)-glyceraldehyde acetonide in an 18% overall yield by a 12-step sequence involving highly diastereoselective ethynylation of an α-alkoxy ketone intermediate. The present synthesis is superior, both in overall yield and in the number of steps, to the previous one which required 18 steps from an expensive starting material and resulted in a modest overall yield of 2.5%.

Development of a predictive model for vitamin D deficiency based on the vitamin D status in young Japanese women: A study protocol.

BACKGROUND: Vitamin D deficiency (VDD) is associated with an increased risk for lifestyle-related diseases. In Japan, VDD is quite prevalent in all age groups, with its high risk in young women. Furthermore, its association during pregnancy with gestational hypertension and low birth weight has also been reported. VDD can be diagnosed by serum 25-hydroxyvitamin D [25(OH)D] levels, which, however, is not suited for screening. Therefore, we will create a predictive model for serum 25(OH)D concentration and prevalence of VDD based on such data as region, sun exposure habit, and vitamin D intake in young women. METHODS: From 2020 to 2022, we conduct a cross-sectional study of 600 young women in four regions of Japan, identify the indices associated with serum 25(OH)D concentrations such as sun exposure habits, habitual vitamin D intake, ultraviolet-B irradiation, seasons (summer and winter) and latitude, and construct prediction models for serum 25(OH)D concentrations and VDD risk. This study has been registered with UMIN-CTR (ID: UMIN000041527). RESULTS: One hundred and fifteen subjects have been collected from 6 institutions in winter as of May 2021. When data from more than 200 subjects have become available, we will conduct the interim analysis, summarize the data by region and facility, review the inclusion criteria for analysis, and check for missing values and outliers. Prediction models for serum 25(OH)D concentration and VDD will be determined in the final analysis when all cases have been collected. CONCLUSIONS: A screening tool for VDD risk to be developed in our study based on the predictive model would help the public and medical professionals prevent lifestyle-related diseases through improving VDD. Additionally, the results may serve as the scientific basis for determining the appropriate vitamin D intake and sun exposure standards.

Control of dry weight and tube feeding improved the general condition of a hemodialysis patient: report of a case.

Patients on long-term hemodialysis are at risk of developing malnutrition,and poor nutrient intake is an important factor in this. In the present case, we encountered a 55-year-old Japanese woman with end-stage renal failure and a past history of schizophrenia. Severe systemic edema was observed. Hemodialysis was started, but after one year she suddenly became unable to consume food orally, despite provision of a dietary plan by the nutrition support team (NST). Tube feeding was eventually implemented. Because the systemic edema did not improve, we decided to remove body fluid by intense hemodialysis. Hypotension was often observed during this hemodialysis, requiring dopamine. Over approximately 2 months, the patient's dry weight fell from 73 kg to 62 kg, the patient's activity improved and she became able to eat orally again, allowing tube feeding to be stopped. Although the reason for the sudden anorexia has not been clarified, tube feeding and dry weight control was successful in the treatment of this malnourished hemodialysis patient.

Identification and characterization of a luciferase isotype in the Japanese firefly, Luciola cruciata, involving in the dim glow of firefly eggs.

We isolated the cDNA of a luciferase isotype (LcLuc2) from the Japanese firefly, Luciola cruciata (Lampyridae, Coleoptera). The gene product of LcLuc2 (LcLuc2) showed 59% amino acid identity with firefly luciferase LcLuc1, which was previously identified in L. cruciata. The recombinant LcLuc2 showed both luminescence activity and fatty acyl-CoA synthetic activity comparable to those of LcLuc1. The spectral maxima of the luminescence by LcLuc1 and LcLuc2 were 554 and 543 nm, respectively. Reverse transcription-PCR analysis showed that the transcripts of LcLuc1 were abundant in the lanterns of larva, adult male, and adult female, whereas both LcLuc1 and LcLuc2 were expressed in eggs. The luminescence spectra of the lantern extracts from larva, adult male, and adult female were in good agreement with that of recombinant LcLuc1. On the other hand, the emission maximum of the extract from eggs was between those of LcLuc1 and LcLuc2. These results suggest that L. cruciata possesses two luciferases: LcLuc1 is responsible for the major luminescence in larva and adult, whereas LcLuc1 and LcLuc2 are responsible for the dim glow in firefly eggs.

Characterization of the reactions of starch branching enzymes from rice endosperm.

To our knowledge the present paper shows for the first time the kinetic parameters of all the three starch branching enzyme (BE) isozymes, BEI, BEIIa and BEIIb, from rice with both amylopectin and synthetic amylose as glucan substrate. The activities of these BE isozymes with a linear glucan amylose decreased with a decrease in the molar size of amylose, and no activities of BEIIa and BEIIb were found when the degree of polymerization (DP) of amylose was lower than at least 80, whereas BEI had an activity with amylose of a DP higher than approximately 50. Detailed analyses of debranched products from BE reactions revealed the distinct chain length preferences of the individual BE isozymes. BEIIb almost exclusively transferred chains of DP7 and DP6 while BEIIa formed a wide range of short chains of DP6 to around DP15 from outer chains of amylopectin and amylose. On the other hand, BEI formed a variety of short chains and intermediate chains of a DP

The primitive rhodophyte Cyanidioschyzon merolae contains a semiamylopectin-type, but not an amylose-type, alpha-glucan.

The storage glucans of Cyanidioschyzon merolae [clade L-1 (cyanidian algae), order Porphyridiales, subclass Bangiophycidae], which is considered to be one of the most primitive rhodophytes, were analyzed to understand the early evolution of the glucan structure in the Rhodophyta. Chain-length distribution analysis of the glucans of cyanidian algae demonstrated that while the glucans of Cyanidium caldarium and Galdieria sulphuraria are of the glycogen type, those of C. merolae are of the semiamylopectin type, as in other lineages of the Rhodophyta. Gel permeation chromatography, however, showed that the glucans of C. merolae do not include amylose, being different from those of other Bangiophycidae species. Identification by MALDI-TOF-MS and enzyme assaying of glucan granule-bound proteins indicated that phosphorylase, but not starch synthase, is included. Thus, C. merolae has an unusual glucan and bound-protein composition for the Bangiophycidae, appearing to be a member of the Florideophycidae. The finding that the alga does not contain amylose or the related enzyme, granule-bound starch synthase, is, however, consistent with previously reported results of molecular phylogenetic analysis of starch synthases. Our results support an evolutionary scenario defined by the loss of starch and reversion to glycogen synthesis during the evolution of cyanidian algae, and suggest the possibility that a C. merolae-like primitive rhodophyte might have evolved into the Florideophycidae.

Chlorella starch branching enzyme II (BEII) can complement the function of BEIIb in rice endosperm.

In monocots, starch branching enzyme II (BEII) was functionally differentiated into BEIIa and BEIIb after separation from the dicots, and in cereals BEIIb plays a distinct role in amylopectin biosynthesis in the endosperm. The present study was conducted to examine to what extent a green algal BEII has an overlapping function with BEIIb in starch biosynthesis by introducing the Chlorella BEII gene into an amylose-extender (ae) mutant of rice. Chlorella BEII was found to complement the contribution of the rice endosperm BEIIb to the structures of amylopectin and starch granules because these mutated phenotypes were recovered almost completely to those of the wild type by the expression of Chlorella BEII. When the recombinant BE enzymes were incubated with the rice ae amylopectin, the branching pattern of Chlorella BEII was much more similar to that of rice BEIIb rather than rice BEIIa. Detailed analyses of BE reaction products suggests that BEIIb and Chlorella BEII only transfer chains with a degree of polymerization (DP) of 6 and 7, whereas BEIIa preferably transfers short chains with a DP of about 6-11. These results show that the Chlorella BEII is functionally similar to rice BEIIb rather than BEIIa.

Characterization of pullulanase (PUL)-deficient mutants of rice (Oryza sativa L.) and the function of PUL on starch biosynthesis in the developing rice endosperm.

Rice (Oryza sativa) allelic sugary1 (sug1) mutants defective in isoamylase 1 (ISA1) accumulate varying levels of starch and phytoglycogen in their endosperm, and the activity of a pullulanase-type of a debranching enzyme (PUL) was found to correlate closely with the severity of the sug1 phenotype. Thus, three PUL-deficient mutants were generated to investigate the function of PUL in starch biosynthesis. The reduction of PUL activity had no pleiotropic effects on the other enzymes involved in starch biosynthesis. The short chains (DP < or = 13) of amylopectin in PUL mutants were increased compared with that of the wild type, but the extent of the changes was much smaller than that of sug1 mutants. The alpha-glucan composition [amylose, amylopectin, water-soluble polysaccharide (WSP)] and the structure of the starch components (amylose and amylopectin) of the PUL mutants were essentially the same, although the average chain length of the B(2-3) chains of amylopectin in the PUL mutant was approximately 3 residues longer than that of the wild type. The double mutants between the PUL-null and mild sug1 mutants still retained starch in the outer layer of endosperm tissue, while the amounts of WSP and short chains (DP < or = 7) of amylopectin were higher than those of the sug1 mutant; this indicates that the PUL function partially overlaps with that of ISA1 and its deficiency has a much smaller effect on the synthesis of amylopectin than ISA1 deficiency and the variation of the sug1 phenotype is not significantly dependent on the PUL activities.

Effect of relaxin and IGF-I on the pre-implantation development of Mongolian gerbil (Meriones unguiculatus) embryos in vitro.

PURPOSE: Both relaxin and insulin-like growth factor (IGF) are members of the insulin super family. This study aimed to investigate the effect of relaxin and IGF-I on the pre-implantation of Mongolian gerbil of blastocyst development in vitro. METHODS: Blastocysts and eight-cell stage embryos were collected from female gerbils. Eight-cell embryos and blastocysts were cultured in mM16 medium supplemented with or without relaxin or IGF-I for 24 h. Blastocysts were counted for total, inner cell mass (ICM) and trophectoderm (TE) cell numbers, and assessed apoptosis incidence. In addition, to measure incorporation of 3H-methionine, blastocysts were cultured for 3 h with relaxin or IGF-I, washed with trichloroacetic acid and measured by liquid scintiration counter. RESULTS: Relaxin (200 ng/ml) increased total, TE and ICM cell numbers of blastocyst (P < 0.05) when it was compared with the control. IGF-I (150 ng/ml) also has influence on total and ICM cell numbers of blastocyst when compared with control. Apoptosis incidence was relatively low, and a significant difference was not observed between each group. The effect of relaxin on incorporation of 3H-methionine was higher than the control group (P < 0.05). Relaxin increased the developmental rate from the eight-cell stage to blastocyst (P < 0.05). CONCLUSIONS: In conclusion, relaxin and IGF-I stimulated protein synthesis and increased cell numbers of blastocysts, promoting development of the gerbil embryo in vitro culture.

Effect of relaxin on the decidual cell reaction in the Mongolian gerbil (Meriones unguiculatus).

PURPOSE: Differentiation of endometrial stromal cells into decidual cells occurs during embryo implantation and pregnancy. Recently, it has been reported that relaxin affects the decidualization of cultured human endometrial cells in vitro; however, there has been no study on the decidualization of the Mongolian gerbil (Meriones unguiculatus). The authors demonstrated artificially induced decidualization, and the effect of relaxin on decidualization in gerbils. METHODS: Ten-to-twelve-week-old female Mongolian gerbils were ovariectomized, treated with estradiol, progesterone, and relaxin, and the uterine horn was stimulated. On day 10, uterine horns were measured for weight, protein concentration, and the incorporation of 14C-methionine; tissue sections were examined. Interleukin-11 (IL-11) primers were used for RT-PCR to confirm decidualization. RESULTS: Decidualization can be induced artificially in gerbils. In general, the histological observations of gerbil decidual cells were very similar to those of rats. The uterine horn weight, protein content, and protein synthesis from 14C-methionine significantly increased in the relaxin-treated gerbils (P< 0.05). Mast cells in the relaxin-treated uterus had proliferated more than those of the non-relaxin-treated group, which was confirmed by IL-11 expression. CONCLUSIONS: We conclude that decidualization can be induced artificially, and relaxin increased weight of uterine horn, protein concentration, protein synthesis and IL-11 expression in gerbils.

A Survey on Health Care and Health Concerning Workers for Considering Appropriate Personal Health Record Service.

To prevent worsening of diabetes mellitus, we conducted a developmental research of personal health record (PHR), whereby affected individuals, medical staff and an insurer cooperate and manage effective treatment. Medical expenses can be suppressed by preventing the onset of lifestyle-related diseases. Companies can benefit from improved employee productivity by promoting healthy and efficient working styles. We conducted a health and medical consciousness survey to examine PHR models that are attractive for both employers and employees.

A direct repeat of E-box-like elements is required for cell-autonomous circadian rhythm of clock genes.

BACKGROUND: The circadian expression of the mammalian clock genes is based on transcriptional feedback loops. Two basic helix-loop-helix (bHLH) PAS (for Period-Arnt-Sim) domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promoter element termed the E-box (CACGTG). The non-canonical E-boxes or E-box-like sequences have also been reported to be necessary for circadian oscillation. RESULTS: We report a new cis-element required for cell-autonomous circadian transcription of clock genes. This new element consists of a canonical E-box or a non-canonical E-box and an E-box-like sequence in tandem with the latter with a short interval, 6 base pairs, between them. We demonstrate that both E-box or E-box-like sequences are needed to generate cell-autonomous oscillation. We also verify that the spacing nucleotides with constant length between these 2 E-elements are crucial for robust oscillation. Furthermore, by in silico analysis we conclude that several clock and clock-controlled genes possess a direct repeat of the E-box-like elements in their promoter region. CONCLUSION: We propose a novel possible mechanism regulated by double E-box-like elements, not to a single E-box, for circadian transcriptional oscillation. The direct repeat of the E-box-like elements identified in this study is the minimal required element for the generation of cell-autonomous transcriptional oscillation of clock and clock-controlled genes.

Blood asymmetric dimethylarginine and nitrite/nitrate concentrations in short-stature children born small for gestational age with and without growth hormone therapy.

Objective To investigate the basal amino acid metabolism and impact of growth hormone (GH) therapy in short-stature children born small for gestational age (short SGA children). Methods In this age-matched case-control study, the basal blood levels of amino acids, asymmetric dimethylarginine (ADMA), and nitrite/nitrate (NOx) were compared between 24 short SGA children and 25 age-matched normal children. Changes in these parameters were assessed for 12 months in 12 short SGA children initiating GH therapy (Group A) and 12 age-matched short SGA children without GH therapy (Group B). Results The arginine levels were significantly lower in the short SGA than in normal children. The ADMA levels were significantly higher and NOx levels were significantly lower in the short SGA than normal children. In Group A, the ADMA level was significantly lower and NOx level was significantly higher at 6 months than at baseline. At 12 months, the ADMA level in Group A began to increase, but the NOx level remained the same. Group B showed no significant changes. Conclusions This study is the first to show that ADMA is promoted and nitric oxide is suppressed in short SGA children and that GH therapy affects the production of ADMA and nitric oxide.