Kale improves bowel movements in constipated women and affects some intestinal microbes and metabolites: a pilot study.

Dietary fiber improves intestinal environments, by, among others, increasing stool frequency. Kale is a good source of dietary fiber and minerals; however, the effects of kale on the intestinal environment have not yet been evaluated. This study determined how the intestinal environment, including the intestinal microbiota and its metabolome, and stool frequency are affected by the consumption of kale, in humans. A randomized controlled crossover trial, with a 4-week consumption of kale or control food, was conducted. An integrated analysis of the intestinal microbiota and metabolome was performed, and their relationship with improvements in stool frequency was analyzed. Kale intake for 4 weeks significantly increased stool frequency and altered some intestinal microbes, such as an increase in the [Eubacterium] eligens group and a decrease in the [Ruminococcus] gnavus group. Analysis of subjects with increased stool frequency revealed that this group had smaller amounts of stool before kale intake. Our findings indicate that kale modifies certain gut microbes, such as [Eubacterium] eligens and [Ruminococcus] gnavus, and improves bowel movements, particularly in those with smaller stool amounts.

Integrated analysis of the oral and intestinal microbiome and metabolome of elderly people with more than 26 original teeth: a pilot study.

Elderly subjects with more than 20 natural teeth have a higher healthy life expectancy than those with few or no teeth. The oral microbiome and its metabolome are associated with oral health, and they are also associated with systemic health via the oral-gut axis. Here, we analyzed the oral and gut microbiome and metabolome profiles of elderly subjects with more than 26 natural teeth. Salivary samples collected as mouth-rinsed water and fecal samples were obtained from 22 healthy individuals, 10 elderly individuals with more than 26 natural teeth and 24 subjects with periodontal disease. The oral microbiome and metabolome profiles of elderly individuals resembled those of subjects with periodontal disease, with the metabolome showing a more substantial differential abundance of components. Despite the distinct oral metabolome profiles, there was no differential abundance of components in the gut microbiome and metabolomes, except for enrichment of short-chain fatty acids in elderly subjects. Finally, to investigate the relationship between the oral and gut microbiome and metabolome, we analyzed bacterial coexistence in the oral cavity and gut and analyzed the correlation of metabolite levels between the oral cavity and gut. However, there were few associations between oral and gut for bacteria and metabolites in either elderly or healthy subjects. Overall, these results indicate distinct oral microbiome and metabolome profiles, as well as the lack of an oral-gut axis in elderly subjects with a high number of natural teeth.

Serum Creatinine Elevation as a Risk Factor for Niraparib-induced Hematologic Toxicity.

BACKGROUND/AIM: Niraparib dosages can be individualized to reduce the starting dose based on body weight and baseline platelet count. However, even with individualized dosing, scattered cases of ≥Grade 3 hematologic toxicity occur. This study explored markers predictive of serious hematologic toxicity in niraparib therapy. PATIENTS AND METHODS: This retrospective observational study investigated patients who started niraparib therapy at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research between December 2020 and March 2022. Associations between hematologic toxicities and serum creatinine ratio (percentage increase in serum creatinine between baseline and after niraparib initiation) were investigated. RESULTS: Out of 50 ovarian cancer patients who initiated niraparib, 45 patients were included in the final analysis. Twenty-three patients (51.1%) developed ≥Grade 3 hematologic toxicity, with neutropenia in 17 (37.8%), anemia in 9 (20.0%), and thrombocytopenia in 4 (8.9%). Patients with Grade 4 hematologic toxicity showed higher serum creatinine ratios than those with ≤Grade 2. Thrombocytopenia ≥Grade 3 occurred only within 2 months of niraparib initiation and was preceded by an increase in serum creatinine in all affected patients. CONCLUSION: Serum creatinine ratio offers a potential marker for predicting severe hematologic toxicity following niraparib therapy.

Comparison of Impressions of COVID-19 Vaccination and Influenza Vaccination in Japan by Analyzing Social Media Using Text Mining.

The aim of this study was to compare impressions of COVID-19 vaccination and influenza vaccination in Japan by analyzing social media (Twitter®) using a text-mining method. We obtained 10,000 tweets using the keywords "corona vaccine" and "influenza vaccine" on 15 December 2022 and 19 February 2023. We then counted the number of times the words were used and listed frequency of these words by a text-mining method called KH Coder. We also investigated concepts in the data using groups of words that often appeared together or groups of documents that contained the same words using multi-dimensional scaling (MDS). "Death" in relation to corona vaccine and "severe disease" for influenza vaccine were frequently used on 15 December 2022. The number of times the word "death" was used decreased, "after effect" was newly recognized for corona vaccine, and "severe disease" was not used in relation to influenza vaccine. Through this comprehensive analysis of social media data, we observed distinct variations in public perceptions of corona vaccination and influenza vaccination in Japan. These findings provide valuable insights for public health authorities and policymakers to better understand public sentiment and tailor their communication strategies accordingly.

Identification of In-Droplet Multicellular Communities by Light-Induced Combinatorial DNA Barcoding.

A microdroplet co-culture system is useful for the parallel assessment of numerous possible cell-cell interactions by generating isolated subcommunities from a pool of heterogeneous cells. However, the integration of single-cell sequencing into such analysis has been limited due to the lack of effective molecular identifiers for each in-droplet subcommunity. Herein, we present a strategy for generating in-droplet subcommunity identifiers using DNA-functionalized microparticles encapsulated within microdroplets. These microparticles serve as initial information carriers, where their combinations act as distinct identifiers for in-droplet subcommunity. Upon optical trigger, DNA barcoding molecules encoding the microparticle information are once released in the microdroplets and then tag cell membranes. The tagged DNA molecules then serve as a second information carrier readable by single-cell sequencing to reconstitute the community in silico in the single-cell RNA sequencing data space.

Integrated gut microbiome and metabolome analyses identified fecal biomarkers for bowel movement regulation by Bifidobacterium longum BB536 supplementation: A RCT.

Background: Bifidobacterium longum BB536 supplementation can be used to regulate bowel movements in various people, including healthy subjects and patients with irritable bowel syndrome (IBS); however, individuals vary in their responses to B. longum BB536 treatment. One putative factor is the gut microbiota; recent studies have reported that the gut microbiota mediates the effects of diet or drugs on the host. Here, we investigated intestinal features, such as the microbiome and metabolome, related to B. longum BB536 effectiveness in increasing bowel movement frequency. Results: A randomized, double-blind controlled crossover trial was conducted with 24 adults who mainly tended to be constipated. The subjects received a two-week dietary intervention consisting of B. longum BB536 in acid-resistant seamless capsules or similarly encapsulated starch powder as the placebo control. Bowel movement frequency was recorded daily, and fecal samples were collected at several time points, and analyzed by metabologenomic approach that consists of an integrated analysis of metabolome data obtained using mass spectrometry and microbiome data obtained using high-throughput sequencing. There were differences among subjects in B. longum intake-induced bowel movement frequency. The responders were predicted by machine learning based on the microbiome and metabolome features of the fecal samples collected before B. longum intake. The abundances of eight bacterial genera were significantly different between responders and nonresponders. Conclusions: Intestinal microbiome and metabolome profiles might be utilized as potential markers of improved bowel movement after B. longum BB536 supplementation. These findings have implications for the development of personalized probiotic treatments.

Metabologenomic Approach Reveals Intestinal Environmental Features Associated with Barley-Induced Glucose Tolerance Improvements in Japanese: A Randomized Controlled Trial.

(1) Background: Consumption of barley has been known to exert beneficial effects on glucose tolerance; however, it has also been reported that there are inter-individual differences in these responses. Recent evidence has suggested that these individual differences are mediated by the gut microbiota. (2) Methods: In the present study, we aimed to understand the relationship between the intestinal environment, including intestinal microbiome and their metabolome, and glucose tolerance. A randomized controlled trial with a 4-week consumption of barley or control food was conducted. We conducted an integrated analysis of the intestinal microbiome and metabolome and analyzed the relationship with improvement of glucose tolerance. (3) Results: We found that metabolites such as azelate were significantly increased after barley consumption. Furthermore, the subjects whose glucose tolerance was slightly impaired showed improvement in their glucose tolerance index following the barley consumption. Additionally, the analysis showed that the increase in the abundance of the Anaerostipes was correlated with the improvement in the glucose tolerance index. (4) Conclusions: Our findings indicate that the effects of barley consumption for glucose tolerance are partly defined by the intestinal environment of consumers, providing a quantitative measurement of the dietary effect based on the intestinal environment.

Pre-Impressions of the Third COVID-19 Vaccination among Medical Staff: A Text Mining-Based Survey.

The aim of this study was to investigate the pre-impressions of the third Coronavirus disease 2019 (COVID-19) vaccination among Japanese medical staff using quantitative analysis. Among 413 medical staff, 260 (60 men and 200 women) aged 40.4 ± 12.3 years were enrolled in this cross-sectional study. Pre-impressions of the third COVID-19 vaccination were analyzed using the text-mining analysis software, KH coder. Among 260 subjects, 242 (93.1%) agreed to the third vaccination, with the rate being lower among subjects in their 30s (87.3%) than those in the other age groups. The word "side effects" was characteristic of subjects in their 20s and nurses, and "pregnancy" of those in their 30s and administrative staff. Pre-impressions of the third COVID-19 vaccination varied among age groups and different professions. The results obtained provide useful information for promoting the third COVID-19 vaccination to Japanese adults.

Resistant Maltodextrin Intake Reduces Virulent Metabolites in the Gut Environment: A Randomized Control Study in a Japanese Cohort.

In recent years, there have been many reports on the effects of prebiotics on intestinal health. In particular, the consumption of resistant maltodextrin (RMD) has been reported to be beneficial. However, there has been no comprehensive quantification of the effect of RMD on the intestinal environment. Therefore, this study aimed to quantify the effects of RMD on the intestine, especially the intestinal microbiome and metabolome profiles. A randomized, double-blind, and controlled trial was conducted in 29 Japanese subjects, whose hemoglobin A1c (HbA1c) levels are larger than 6% (Clinical trial no. UMIN000023970, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027589). The subjects consumed RMD or placebo twice per day for 24 weeks. Blood and fecal samples were collected before and after the intake. The intestinal environment was assessed by a metabologenomics approach, involving 16S rRNA gene-based microbiome analysis and mass spectrometry-based metabolome analysis. The intake of RMD increased the levels of Bifidobacterium and Fusicatenibacter and decreased deoxycholate levels. Additionally, intake of RMD lowered the levels of some opportunistic virulent metabolites, such as imidazole propionate and trimethylamine, in subjects with an initially high amount of those metabolites. RMD may have beneficial effects on the gut environment, such as commensal microbiota modulation and reduction of virulence metabolites, which is known as a causative factor in metabolic disorders. However, the effects of RMD partially depend on the gut environmental baseline.

The Nutritional Efficacy of Chlorella Supplementation Depends on the Individual Gut Environment: A Randomised Control Study.

Recent studies have accumulated evidence that the intestinal environment is strongly correlated with host diet, which influences host health. A number of dietary products whose mechanisms of influence operate via the gut microbiota have been revealed, but they are still limited. Here, we investigated the dietary influence of Chlorella, a green alga commercially available as a dietary supplement. A randomised, double-blind, placebo-controlled crossover trial including 40 Japanese participants with constipation was performed. In this study, the primary outcome and secondary outcome were set as defecation frequency and blood folate level, respectively. In both outcomes, no significant differences were detected compared to the control intake. Therefore, we analysed the gut microbiome, gut metabolome, and blood parameters in an integrated manner as an exploratory analysis. We revealed that the consumption of Chlorella increased the level of several dicarboxylic acids in faeces. Furthermore, the analysis showed that individuals with low concentrations of faecal propionate showed an increase in propionate concentration upon Chlorella intake. In addition, increasing blood folate levels were negatively correlated with defecation frequency at baseline. Our study suggested that the effect of Chlorella consumption varies among individuals depending on their intestinal environment, which illustrates the importance of stratified dietary management based on the intestinal environment in individuals.

A hypomorphic variant in EYS detected by genome-wide association study contributes toward retinitis pigmentosa.

The genetic basis of Japanese autosomal recessive retinitis pigmentosa (ARRP) remains largely unknown. Herein, we applied a 2-step genome-wide association study (GWAS) in 640 Japanese patients. Meta-GWAS identified three independent peaks at P < 5.0 × 10-8, all within the major ARRP gene EYS. Two of the three were each in linkage disequilibrium with a different low frequency variant (allele frequency < 0.05); a known founder Mendelian mutation (c.4957dupA, p.S1653Kfs*2) and a non-synonymous variant (c.2528 G > A, p.G843E) of unknown significance. mRNA harboring c.2528 G > A failed to restore rhodopsin mislocalization induced by morpholino-mediated knockdown of eys in zebrafish, consistent with the variant being pathogenic. c.2528 G > A solved an additional 7.0% of Japanese ARRP cases. The third peak was in linkage disequilibrium with a common non-synonymous variant (c.7666 A > T, p.S2556C), possibly representing an unreported disease-susceptibility signal. GWAS successfully unraveled genetic causes of a rare monogenic disorder and identified a high frequency variant potentially linked to development of local genome therapeutics.

Longitudinal effects of caregiving on parental well-being: the example of Rett syndrome, a severe neurological disorder.

Little longitudinal research has examined parental well-being in those with a child with specific genetic developmental disorder although the associated severe neurological impairments and multiple physical comorbidities likely place substantial burden of caregiving on the parent. We aimed to examine longitudinally the well-being of parents of individuals included in the Australian Rett Syndrome Database over the period from 2002 to 2011 using the Short Form 12 Health Survey. Residential remoteness, the child being a teenager at baseline, having frequent sleep disturbances or behavioural problems, and the type of MECP2 gene mutation were each associated with later poorer parental physical well-being scores. Being a single parent or on a low income was also associated with later poorer physical well-being, while the child having enteral feeding was associated with later poorer emotional well-being. Both the physical and emotional well-being of the parent improved if the child was living in out-of-home care. Our findings suggest that some opportunities do exist for clinicians to help optimise parental well-being. Being alert to the possibility and need for management of a child's sleep or emotional disturbance is important as is awareness of the additional likely parental burden as the child moves through adolescence into early adulthood and their need for additional support at that time. However, the findings also highlight the complex nature of parental well-being over time in parents of children with a severe neurological disorder and how they may be affected by a range of inter-related family and child factors.

Contribution of a lectin, LecM, to the quorum sensing signalling pathway of Ralstonia solanacearum strain OE1-1.

The soil-borne bacterium Ralstonia solanacearum invades the roots and colonizes the intercellular spaces and then the xylem. The expression of lecM, encoding a lectin LecM, is induced by an OmpR family response regulator HrpG in R. solanacearum strain OE1-1. LecM contributes to the attachment of strain OE1-1 to the host cells of intercellular spaces. OE1-1 produces methyl 3-hydroxymyristate (3-OH MAME) through a methyltransferase (PhcB) and extracellularly secretes the chemical as a quorum sensing (QS) signal, which activates QS. The expression of lecM is also induced by the PhcA virulence regulator functioning through QS, and the resulting LecM is implicated in the QS-dependent production of major exopolysaccharide EPS I and the aggregation of OE1-1 cells. To investigate the function of LecM in QS, we analysed the transcriptome of R. solanacearum strains generated by RNA sequencing technology. In the lecM mutant, the expression of positively QS-regulated genes and negatively QS-regulated genes was down-regulated (by >90%) and up-regulated (by ~60%), respectively. However, phcB and phcA in the lecM mutant were expressed at levels similar to those in strain OE1-1. The lecM mutant produced significantly less ralfuranone and exhibited a significantly greater swimming motility, which were positively and negatively regulated by QS, respectively. In addition, the extracellular 3-OH MAME content of the lecM mutant was significantly lower than that of OE1-1. The application of 3-OH MAME more strongly increased EPS I production in the phcB-deleted mutant and strain OE1-1 than in the lecM mutant. Thus, the QS-dependent production of LecM contributes to the QS signalling pathway.

Chronological Observations of Iris Flocculi in a Japanese Family with Thoracic Aortic Aneurysm and Dissections.

Iris flocculi, a type of hereditary iris pigment epithelial cyst, have been reported in association with smooth muscle α-2 actin (ACTA2) gene as the causative gene of familial thoracic aortic aneurysm and dissections (FTAAD). The purpose of the report was to examine morphological changes in the shape of flocculi and iris features over time by comparing infants to adults with FTAAD combined with iris flocculi. A Japanese family with FTAAD and bilateral iris flocculi and the Arg149Cys gene mutation was included. A slit-lamp photograph and anterior segment optical coherence tomography (AS-OCT) were used to evaluate the structure and location of iris flocculi. AS-OCT was also used to measure the internal shape and iris thickness of the dilated pupil muscle. A morphological change in the cyst was confirmed to be existent in the youngest cases. Pigment discoloration and iris atrophy of the iris body were observed in all cases. Besides, a decrease in iris thickness was observed with AS-OCT measurement. Changes across generations in iris flocculi occurred in a Japanese family with TAAD. ACTA2 gene abnormalities may cause iris atrophy and decrease thickness in addition to iris flocculi in early life. The prognosis is poor when FTAAD is combined with iris flocculi, and prevention of cardiovascular disease is necessary based on earlier findings of its emergence.

Comparing Parental Well-Being and Its Determinants Across Three Different Genetic Disorders Causing Intellectual Disability.

Using the Short Form 12 Health Survey this cross-sectional study examined parental well-being in caregivers of children with one of three genetic disorders associated with intellectual disability; Down syndrome, Rett syndrome and the CDKL5 disorder. Data were sourced from the Western Australian Down Syndrome (n = 291), Australian Rett Syndrome (n = 187) and International CDKL5 Disorder (n = 168) Databases. Among 596 mothers (median age, years 43.7; 24.6-72.2), emotional well-being was poorer than general female populations across age groups. Multivariate linear regression identified the poorest well-being in parents of children with the CDKL5 disorder, a rare but severe and complex encephalopathy, and negative associations with increased clinical severity irrespective of diagnosis. These findings are important for those providing healthcare and social services for these populations.

Ralfuranones contribute to mushroom-type biofilm formation by Ralstonia solanacearum strain OE1-1.

After invasion into intercellular spaces of tomato plants, the soil-borne, plant-pathogenic Ralstonia solanacearum strain OE1-1 forms mushroom-shaped biofilms (mushroom-type biofilms, mBFs) on tomato cells, leading to its virulence. The strain OE1-1 produces aryl-furanone secondary metabolites, ralfuranones (A, B, J, K and L), dependent on the quorum sensing (QS) system, with methyl 3-hydroxymyristate (3-OH MAME) synthesized by PhcB as a QS signal. Ralfuranones are associated with the feedback loop of the QS system. A ralfuranone productivity-deficient mutant (ΔralA) exhibited significantly reduced growth in intercellular spaces compared with strain OE1-1, losing its virulence. To analyse the function of ralfuranones in mBF formation by OE1-1 cells, we observed cell aggregates of R. solanacearum strains statically incubated in tomato apoplast fluids on filters under a scanning electron microscope. The ΔralA strain formed significantly fewer microcolonies and mBFs than strain OE1-1. Supplementation of ralfuranones A, B, J and K, but not L, significantly enhanced the development of mBF formation by ΔralA. Furthermore, a phcB- and ralA-deleted mutant (ΔphcB/ralA) exhibited less formation of mBFs than OE1-1, although a QS-deficient, phcB-deleted mutant formed mBFs similar to OE1-1. Supplementation with 3-OH MAME significantly reduced the formation of mBFs by ΔphcB/ralA. The application of each ralfuranone significantly increased the formation of mBFs by ΔphcB/ralA supplied with 3-OH MAME. Together, our findings indicate that ralfuranones are implicated not only in the development of mBFs by strain OE1-1, but also in the suppression of QS-mediated negative regulation of mBF formation.

Involvement of ralfuranones in the quorum sensing signalling pathway and virulence of Ralstonia solanacearum strain OE1-1.

The soil-borne, plant-pathogenic Ralstonia solanacearum strain OE1-1 produces and secretes methyl 3-hydroxymyristate (3-OH MAME) as a quorum sensing (QS) signal, which contributes to its virulence. A global virulence regulator, PhcA, functioning through the QS system, positively regulates the expression of ralA, which encodes furanone synthase, to produce aryl-furanone secondary metabolites, ralfuranones. A ralfuranone-deficient mutant (ΔralA) is weakly virulent when directly inoculated into tomato xylem vessels. To investigate the functions of ralfuranones, we analysed R. solanacearum transcriptome data generated by RNA sequencing technology. ΔralA expressed phcB, which is associated with 3-OH MAME production, and phcA at levels similar to those in strain OE1-1. In addition, ΔralA exhibited down-regulated expression of more than 90% of the QS positively regulated genes, and up-regulated expression of more than 75% of the QS negatively regulated genes. These results suggest that ralfuranones affect the QS feedback loop. Ralfuranone supplementation restored the ability of ΔralA cells to aggregate. In addition, ralfuranones A and B restored the swimming motility of ΔralA to wild-type levels. However, the application of exogenous ralfuranones did not affect the production of the major exopolysaccharide, EPS I, in ΔralA. Quantitative real-time polymerase chain reaction assays revealed that the deletion of ralA results in the down-regulated expression of vsrAD and vsrBC, which encode a sensor kinase and a response regulator, respectively, in the two-component regulatory systems that influence EPS I production. The application of ralfuranone B restored the expression of these two genes. Overall, our findings indicate that integrated signalling via ralfuranones influences the QS and virulence of R. solanacearum.

Regulation Involved in Colonization of Intercellular Spaces of Host Plants in Ralstonia solanacearum.

A soil-borne bacterium Ralstonia solanacearum invading plant roots first colonizes the intercellular spaces of the root, and eventually enters xylem vessels, where it replicates at high levels leading to wilting symptoms. After invasion into intercellular spaces, R. solanacearum strain OE1-1 attaches to host cells and expression of the hrp genes encoding components of the type III secretion system (T3SS). OE1-1 then constructs T3SS and secrets effectors into host cells, inducing expression of the host gene encoding phosphatidic acid phosphatase. This leads to suppressing plant innate immunity. Then, OE1-1 grows on host cells, inducing quorum sensing (QS). The QS contributes to regulation of OE1-1 colonization of intercellular spaces including mushroom-type biofilm formation on host cells, leading to its virulence. R. solanacearum strains AW1 and K60 produce methyl 3-hydroxypalmitate (3-OH PAME) as a QS signal. The methyltransferase PhcB synthesizes 3-OH PAME. When 3-OH PAME reaches a threshold level, it increases the ability of the histidine kinase PhcS to phosphorylate the response regulator PhcR. This results in elevated levels of functional PhcA, the global virulence regulator. On the other hand, strains OE1-1 and GMI1000 produce methyl 3-hydroxymyristate (3-OH MAME) as a QS signal. Among R. solanacearum strains, the deduced PhcB and PhcS amino acid sequences are related to the production of QS signals. R. solanacearum produces aryl-furanone secondary metabolites, ralfuranones, which are extracellularly secreted and required for its virulence, dependent on the QS. Interestingly, ralfuranones affect the QS feedback loop. Taken together, integrated signaling via ralfuranones influences the QS, contributing to pathogen virulence.

Intravenous injection of umbilical cord-derived mesenchymal stromal cells attenuates reactive gliosis and hypomyelination in a neonatal intraventricular hemorrhage model.

Intraventricular hemorrhage (IVH) is a frequent complication of preterm newborns, resulting in cerebral palsy and cognitive handicap as well as hypoxic ischemic encephalopathy and periventricular leukomalacia. In this study, we investigated the restorative effect on neonatal IVH by umbilical cord-derived mesenchymal stromal cells (UC-MSCs) cultured in serum-free medium (RM medium) for clinical application. UC-MSCs were cultured with αMEM medium supplemented with FBS or RM. A neonatal IVH mouse model at postnatal day 5 was generated by intraventricular injection of autologous blood, and mice were intravenously administered 1×105 UC-MSCs two days after IVH. Brain magnetic resonance imaging was performed at postnatal day 15, 22 and neurological behavioral measurements were performed at postnatal day 23, accompanied by histopathological analysis and cytokine bead assays in serum after IVH with or without UC-MSCs. Both UC-MSCs cultured with αMEM and RM met the criteria of MSCs and improved behavioral outcome of IVH mice. Moreover the RM group exhibited significant behavioral improvement compared to the control group. Histopathological analysis revealed UC-MSCs cultured with RM significantly attenuated periventricular reactive gliosis, hypomyelination, and periventricular cell death observed after IVH. Furthermore, human brain-derived neurotrophic factor and hepatocyte growth factor were elevated in the serum, cerebrospinal fluid and brain tissue of neonatal IVH model mice 24h after UC-MSCs administration. These results suggest UC-MSCs attenuate neonatal IVH by protecting gliosis and apoptosis of the injured brain, and intravenous injection of UC-MSCs cultured in RM may be feasible for neonatal IVH in clinic.

Impacts of caring for a child with the CDKL5 disorder on parental wellbeing and family quality of life.

BACKGROUND: Although research in this area remains sparse, raising a child with some genetic disorders has been shown to adversely impact maternal health and family quality of life. The aim of this study was to investigate such impacts in families with a child with the CDKL5 disorder, a newly recognised genetic disorder causing severe neurodevelopmental impairments and refractory epilepsy. METHODS: Data were sourced from the International CDKL5 Disorder Database to which 192 families with a child with a pathogenic CDKL5 mutation had provided data by January 2016. The Short Form 12 Health Survey Version 2, yielding a Physical Component Summary and a Mental Component Summary score, was used to measure primary caregiver's wellbeing. The Beach Center Family Quality of Life Scale was used to measure family quality of life. Linear regression analyses were used to investigate relationships between child and family factors and the various subscale scores. RESULTS: The median (range) age of the primary caregivers was 37.0 (24.6-63.7) years and of the children was 5.2 (0.2-34.1) years. The mean (SD) physical and mental component scores were 53.7 (8.6) and 41.9 (11.6), respectively. In mothers aged 25-54 years the mean mental but not the physical component score was lower than population norms. After covariate adjustment, caregivers with a tube-fed child had lower mean physical but higher mean mental component scores than those whose child fed orally (coefficient = -4.80 and 6.79; p = 0.009 and 0.012, respectively). Child sleep disturbances and financial hardship were negatively associated with the mental component score. The mean (SD) Beach Center Family Quality of Life score was 4.06 (0.66) and those who had used respite services had lower scores than those who had not across the subscales. CONCLUSIONS: Emotional wellbeing was considerably impaired in this caregiver population, and was particularly associated with increased severity of child sleep problems and family financial difficulties. Family quality of life was generally rated lowest in those using respite care extensively, suggesting that these families may be more burdened by daily caregiving.