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Supplementary Figure 1 from Inflammatory Processes Triggered by Helicobacter pylori Infection Cause Aberrant DNA Methylation in Gastric Epithelial Cells

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Supplementary Figure 2 from Inflammatory Processes Triggered by Helicobacter pylori Infection Cause Aberrant DNA Methylation in Gastric Epithelial Cells

Supplementary Figure Legends 1-8 from Inflammatory Processes Triggered by Helicobacter pylori Infection Cause Aberrant DNA Methylation in Gastric Epithelial Cells

Supplementary Figure 3 from Inflammatory Processes Triggered by Helicobacter pylori Infection Cause Aberrant DNA Methylation in Gastric Epithelial Cells

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Purpose To determine the influence of a patient education and care program on the quality of life (QOL) of female patients undergoing non‐assisted reproductive technology (ART) fertility treatment. Methods Participants completed the MOS 36‐Item Short‐Form Health Survey and fertility QOL (FertiQoL) questionnaires at baseline and at 3, 6, and 12 months of treatment. The responses of patients who underwent three sessions of the program (at baseline, 3 months, and 6 months of treatment) were compared with those of patients who did not receive the program. Results This study compared 69 patients who received an additional care program with 104 patients in the control group, all from 13 facilities. Treatment FertiQoL responses (p = 0.004) and treatment tolerability (p = 0.043) differed between the program and control groups at 3 months using the repeated measures mixed model. The cost of treatment per pregnancy was lower in the program group than in the control group. Conclusion The patient education and care program provided by reproductive fertility specialists or fertility nurses during non‐ART fertility programs improves patient satisfaction.

Land plants are constantly exposed to environmental stresses and have developed complicated defense systems, including DNA damage response (DDR) and DNA repair systems, to protect plant cells. In Arabidopsis (Arabidopsis thaliana), the transcription factor SUPPRESSOR OF GAMMA RESPONSE1 (SOG1) plays a key role in DDR. Here, we focus on DDR in rice (Oryza sativa)—thought to be a simpler system compared with Arabidopsis due to lack of induction of the endocycle even under DNA damage stress. Rice SOG1 (OsSOG1) and SOG1-like (OsSGL) were identified as putative AtSOG1 orthologs with complete or partial conservation of the serine–glutamine motifs involved in activation via phosphorylation. In addition to OsSOG1 or OsSGL knockout mutants, OsSOG1 nonphosphorylatable mutants (OsSOG1-7A) were generated by homologous recombination-mediated gene targeting. Based on the analysis of DNA damage susceptibility and the effect on the expression of DNA repair-related genes using these mutants, we have demonstrated that OsSOG1 plays a more important role than OsSGL in controlling DDR and DNA repair. OsSOG1-regulated target genes via CTT (N)7 AAG motifs reported previously as AtSOG1 recognition sites. The loss of transcription activity of OsSOG1-7A was not complete compared with OsSOG1-knockout mutants, raising the possibility that other phosphorylation sites might be involved in, or that phosphorylation might not be always required for, the activation of OsSOG1. Furthermore, our findings have highlighted differences in SOG1-mediated DDR between rice and Arabidopsis, especially regarding the transcriptional induction of meiosis-specific recombination-related genes and the response of cell cycle-related genes, revealing rice-specific DDR mechanisms.

Background Pelvic floor muscles support the pelvic organs and control voiding. The first choice in the repair of pelvic floor function that is damaged during pregnancy and delivery is pelvic floor muscle training, which involves repeated muscle relaxation and contraction. However, as muscle contractions cannot be visualised, it is difficult to assess whether patients understand how to contract them. Therefore, we assessed patients’ comprehension of pelvic floor muscle contraction by comparing two teaching methods, vaginal palpation and transabdominal ultrasound, following vaginal delivery. We hypothesised that vaginal palpation is better than transabdominal ultrasound in this regard. Methods This randomised controlled trial conducted in facilities in Tokyo, Japan between July 2018 and January 2019 included women aged ≥ 20 years at 4–6 weeks after vaginal delivery. The randomisation involved website-based centralised allocation. The primary outcome was a change in bladder base displacement during pelvic floor muscle contraction before and after training, which was measured using transabdominal ultrasound. Participants performed three contractions for 3 s, and the mean value was used for statistical analysis. The secondary outcome was a change in understanding the contraction before and after training, which was measured using a five-point Likert scale questionnaire. Outcomes were analysed using Welch’s t-test. Results Sixty-five participants were randomly allocated to the vaginal palpation group (n = 32) and transabdominal ultrasound group (n = 33). Baseline characteristics were similar between the groups. Changes in bladder base displacement were not significantly different between the groups (p = 0.181). Within-group analyses showed that bladder base displacement was large in both groups after the respective intervention. There were no significant differences in any of the outcomes between the two groups before and after the intervention. Conclusions Vaginal palpation and transabdominal ultrasound might be useful for comprehending pelvic floor muscle contraction after vaginal delivery. Trial registration: UMIN 000032304. Registered 18 April 2018, https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000036820.

Higher plants are constantly exposed to environmental stresses, and therefore complicated defense systems, including DNA damage response (DDR) and DNA repair systems, have developed to protect plant cells. In Arabidopsis, the transcription factor SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1) has been reported to play a key role in DDR. Here, we focus on DDR in rice—thought to be a simpler system compared with Arabidopsis due to lack of induction of endocycle even under DNA damage stress. Rice SOG1 (OsSOG1) and SOG1-like (OsSGL) were identified as putative AtSOG1 orthologs with complete or partial conservation of the serine-glutamine (SQ) motifs involved in activation via phosphorylation. In addition to OsSOG1- or OsSGL-knockout mutants, OsSOG1 non-phosphorylatable mutants (OsSOG1-7A) were generated by homologous recombination-mediated gene targeting. Based on DNA damage susceptibility and transcriptome analysis using these mutants, we demonstrated that OsSOG1, but not OsSGL, plays a central role in the DDR and DNA repair. OsSOG1 regulated target genes via CTT (N)7 AAG motifs reported previously as AtSOG1 recognition sites. The loss of transcription activities and DNA damage tolerance of OsSOG1-7A was not complete compared with OsSOG1-knockout mutants, raising the possibility that another phosphorylation site might be involved in the activation of OsSOG1. Furthermore, our findings have highlighted differences in SOG1-mediated DDR between rice and Arabidopsis, especially regarding induction of cell-cycle arrest and endocycle arrest, revealing rice-specific DDR mechanisms.One sentence summaryRice transcription factor SUPPRESSOR OF GAMMA RESPONSE 1 controls DNA damage response and DNA repair through activation via phosphorylation and the direct regulation of expression of numerous genes.

DNA demethylation therapy is now expanding from hematological tumors to solid tumors. To exploit its maximum efficacy, long-term treatment is needed, and stratification of sensitive patients is critically important. Here, we identified a long non-coding RNA, LINC00162, as highly and frequently expressed in gastric cancer cell lines sensitive to 5-aza-2'-deoxycytidine (5-aza-dC). Knockdown of LINC00162 decreased the sensitivity while its overexpression increased the sensitivity. In vivo experiments also showed that LINC00162 overexpression increased the sensitivity. LINC00162 enhanced cell cycle arrest and apoptosis induced by 5-aza-dC, but did not affect its DNA demethylation effect. Mechanistically, LINC00162 interacted with an RNA splicing protein, HNRNPH1, and decreased splicing of an anti-apoptotic splicing variant, BCL-XL. LINC00162 may have translational value to predict patients who will respond to 5-aza-dC.

BACKGROUND: The CpG island methylator phenotype of neuroblastoma (NBL) is strongly associated with poor prognosis and can be targeted by 5-aza-2’-deoxycytidine (5-aza-dC). Differentiation therapy is a standard maintenance therapy for high-risk NBLs. However, the in vivo effect of tamibarotene, a synthetic retinoic acid, and the efficacy of its combination with 5-aza-dC have not been studied. Here, we conducted a preclinical study to assess the in vivo tamibarotene effect and the combination. METHODS: Treatment effects were analysed by in vitro cell growth and differentiation state and by in vivo xenograft suppression. Demethylated genes were analysed by DNA methylation microarrays and geneset enrichment. RESULTS: Tamibarotene monotherapy induced neural extension and upregulation of differentiation markers of NBL cells in vitro, and tumour regression without severe side effects in vivo. 5-Aza-dC monotherapy suppressed tumour growth both in vitro and in vivo, and induced demethylation of genes related to nervous system development and function. Pre-treatment with 5-aza-dC in vitro enhanced upregulation of differentiation markers and genes involved in retinoic acid signaling. Pre-treatment with 5-aza-dC in vivo significantly suppressed tumour growth and reduced the variation in tumour sizes. CONCLUSIONS: Epigenetic drug-based differentiation therapy using 5-aza-dC and TBT is a promising strategy for refractory NBLs.

Gene targeting (GT) enables precise genome modification—e.g., the introduction of base substitutions—using donor DNA as a template. Combined with clean excision of the selection marker used to select GT cells, GT is expected to become a standard, generally applicable, base editing system. Previously, we demonstrated marker excision via a piggyBac transposon from GT-modified loci in rice. However, piggyBac-mediated marker excision has the limitation that it recognizes only the sequence TTAA. Recently, we proposed a novel and universal precise genome editing system consisting of GT with subsequent single-strand annealing (SSA)-mediated marker excision, which has, in principle, no limitation of target sequences. In this study, we introduced base substitutions into the microRNA miR172 target site of the OsCly1 gene—an ortholog of the barley Cleistogamy1 gene involved in cleistogamous flowering. To ensure efficient SSA, the GT vector harbors 1.2-kb overlapped sequences at both ends of a selection marker. The frequency of positive–negative selection-mediated GT using the vector with overlapped sequences was comparable with that achieved using vectors for piggyBac-mediated marker excision without overlapped sequences, with the frequency of SSA-mediated marker excision calculated as ~40% in the T0 generation. This frequency is thought to be adequate to produce marker-free cells, although it is lower than that achieved with piggyBac-mediated marker excision, which approaches 100%. To date, introduction of precise substitutions in discontinuous multiple bases of a targeted gene using base editors and the prime editing system based on CRISPR/Cas9 has been quite difficult. Here, using GT and our SSA-mediated marker excision system, we succeeded in the precise base substitution not only of single bases but also of artificial discontinuous multiple bases in the miR172 target site of the OsCly1 gene. Precise base substitution of miRNA target sites in target genes using this precise genome editing system will be a powerful tool in the production of valuable crops with improved traits.

HER2-positive breast cancers that achieve pathological complete response (pCR) after HER2-directed therapy consistently have good survival. We previously identified HSD17B4 methylation as a marker for pCR by methylation screening. Here, we aimed to identify a new marker by conducting a multi-omics analysis of materials prepared by laser capture microdissection, and adding 71 new samples. In the screening set (n = 36), mutations, methylation, and expression were analyzed by targeted sequencing, Infinium 450 K, and expression microarray, respectively, and 15 genes were identified as differentially expressed and eight genomic regions as differentially methylated between cancer samples with and without pCR. In a validation set (n = 47), one gene showed differential expression, and one region had differential methylation. Further, in the re-validation set (n = 55), all new samples, only HSD17B4 methylation was significantly different. The HSD17B4 methylation was at the transcriptional start site of its major variant, and was associated with its silencing. HSD17B4 was highly expressed in the vast majority of human cancers, and its methylation was present only in breast cancers and one lymphoblastic leukemia cell line. A combination of estrogen receptor-negative status and HSD17B4 methylation showed a positive predictive value of 80.0%. During HER2-directed neoadjuvant therapy, HSD17B4 methylation was the most reliable marker to monitor response to the therapy. These results showed that HSD17B4 methylation is a candidate predictive and response marker of HER2-positive breast cancer to HER2-directed therapy.

Plant posture is controlled by various environmental cues, such as light, temperature, and gravity. The overall architecture is determined by the growth angles of lateral organs, such as roots and branches. The branch growth angle affected by gravity is known as the gravitropic setpoint angle (GSA), and it has been proposed that the GSA is determined by balancing two opposing growth components: gravitropism and anti-gravitropic offset (AGO). The molecular mechanisms underlying gravitropism have been studied extensively, but little is known about the nature of the AGO. Recent studies reported the importance of LAZY1-LIKE (LZY) family genes in the signaling process for gravitropism, such that loss-of-function mutants of LZY family genes resulted in reversed gravitropism, which we term it here as the &ldquo, anti-gravitropic&rdquo, phenotype. We assume that this peculiar phenotype manifests as the AGO due to the loss of gravitropism, we characterized the &ldquo, phenotype of Arabidopsis lzy multiple mutant genetically and physiologically. Our genetic interaction analyses strongly suggested that gravity-sensing cells are required for the &ldquo, phenotype in roots and lateral branches. We also show that starch-filled amyloplasts play a significant role in the &ldquo, phenotype, especially in the root of the lzy multiple mutant.

A successful example of transposon deletion via CRISPR/Cas9-mediated genome editing suggests a novel alternative approach to plant breeding. Transposition of transposable elements (TEs) can affect adjacent genes, leading to changes in genetic traits. Expression levels and patterns, splicing and epigenetic status, and function of genes located in, or near, the inserted/excised locus can be affected. Artificial modification of loci adjacent to TEs, or TEs themselves, by genome editing could mimic the translocation of TEs that occurs in nature, suggesting that it might be possible to produce novel plants by modification of TEs via genome editing. To our knowledge, there are no reports thus far of modification of TEs by genome editing in plants. In this study, we performed targeted deletion of the Tos17 retrotransposon, which is flanked at both ends by long terminal repeat (LTR) sequences, via genome editing in rice. We succeeded in targeted mutagenesis of the LTR, and targeted deletion between LTRs, in calli transformed with CRISPR/Cas9 vectors for the Tos17 LTR. Moreover, we also successfully obtained regenerated plants derived from transformed calli and plants homozygous for lacking Tos17 in the next generation. Taken together, our results demonstrate successful deletion of the Tos17 retrotransposon from the rice genome by targeted mutagenesis using CRISPR/Cas9. We believe that this strategy could be applied to other TEs in many plant species, providing a rapid breeding technology as an alternative means to re-activate expression of agronomically important genes that have been inactivated by TE insertion, especially in plants such as fruit trees, in which it is difficult to maintain parental agronomical traits by cross-breeding due to high heterozygosity.

The ubiquitin ligase F‐box and WD repeat domain‐containing 7 (FBXW7) is responsible for degrading diverse oncoproteins and is considered a tumor suppressor in many human cancers. Inhibiting FBXW7 enhances the malignant potential of several cancers. In this study, we aimed to investigate the role of FBXW7 in cholangiocarcinoma. We found that FBXW7 expression was associated with clinicopathological outcomes in cholangiocarcinoma patients. Both disease‐free and overall survival were significantly worse in the low‐FBXW7 group than in the high‐FBXW7 group (P = .001 and P

Background: FertiQoL, which measures the Quality of Life (QOL) of reproductive partners, has been translated and used in 45 languages in the world. The reliability and validity of the original English version of FertiQoL have been confirmed. However, there is still no report on the reliability and validity of the Japanese version by a large-scale survey. This study aimed to examine the reliability and validity of the Japanese version of the FertiQoL scale for measuring the QOL of patients with reproductive problems. Methods: An unsigned self-filled questionnaire survey was conducted in patients undergoing infertility treatment at seven facilities in the Kanto area in Japan using the 34 items of the Japanese version of the FertiQoL scale. The study design was quantitative cross-sectional descriptive research. The investigation period was from April 2013 to April 2018. The contents of the investigation were attributes, FertiQoL scale, and distress scale. To determine the construct validity, principal component analysis, confirmatory factor analysis, and correlation analysis for each subscale were performed using SPSS Statistics Ver. 23.0 and AMOS Ver. 23.0. The study was performed after obtaining approval from the Research Ethics Review Committee of the responsible institutions to which the researchers belong as an ethical consideration. Results: The participants included 1201 patients undergoing infertility treatment and who provided valid responses. The Cronbach’s α was 0.92, and confirmatory factor analysis identified six domains with 34 items that showed the following values: goodness of fit index = 0.877, adjusted goodness of fit index = 0.855, comparative fit index = 0.893, and root mean square error of approximation = 0.059. The correlation coefficient was 0.669 (p < 0.001) with the distress scale. Conclusions: The Japanese version of FertiQoL showed adequate reliability and validity for assessing the QOL of patients with reproductive problems in Japan.

Background: This study aimed to clarify the supportive care needs and medical care requests of male patients during their infertility treatment to be able to provide them with optimal nursing care. Methods: A self-filled questionnaire survey was conducted in 411 male patients who were undergoing infertility treatment at 4 human reproductive clinics. The investigation period was from April to August 2016. This research used across-sectional study design. The submission of the filled questionnaire was taken as an indication of agreement and consent to the research. The main contents of the questionnaire were attributions, care needs, and medical care requests of male patients. The care needs were evaluated by descriptive statistics, and the free descriptions of the medical care requests were analyzed for their contents qualitatively and recursively. The study was performed after the approval of the Research Ethics Review Committee. Results: The number of valid responses was 331 (80.5%). The care needs of the male patients were warm care from their wives, provision of information on their treatment, daily life information for conceiving, and evaluation data. The 6 categories of the open-ended responses were as follows: warm support, improvement of examination environment, adjustment of medical examination schedule, information provision, support from wife, and subsidy for treatment costs. These were extracted from the medical care requests by qualitative inductive analysis. Conclusions: The care needs and medical care requests of male patients undergoing infertility treatment were mainly on being provided information and supporting their wives. As supporting nursing care for these male patients, provision of sufficient information regarding the examination results and infertility treatment is recommended, and environmental considerations peculiar to male patients are necessary. Consideration from female patients is also an indispensable factor similarly to the provision of care for male patients.

Purpose: The aims of this study were to clarify the complaints and concerns expressed by couples that included a partner with male infertility, certified infertility nurses’ nursing practice and perceptions of nursing for these couples, and factors related to these perceptions and practices. Methods: A quantitative cross-sectional study was conducted. Prospective participants were sent an anonymous self-administered questionnaire containing items pertaining to the complaints and concerns expressed by couples that included a partner with male infertility, and nursing practice and perceptions of nursing for these couples. Results: In total, 133 questionnaires were distributed, 74 responses were received, and 69 of these responses were valid. Couples’ complaints and concerns consisted of a three-factor structure comprising psychological burden, lack of knowledge and information, and problems with partners. Nurses reported that the complaints and concerns of couples that included a partner with male infertility differed between male and female partners. Factors related to nursing practice and nurses’ perceptions of nursing were identified. Conclusions: Participants felt that psychological burden and problems were more serious for female partners than they were for male partners, and concern regarding the physical health of the partner receiving treatment was greater in male partners than it was in female partners.

Bromodomain and extra-terminal (BET) inhibitors suppress super-enhancers and show cytotoxicity against multiple types of tumors. However, early clinical trials with BET inhibitors showed severe hematopoietic toxicities, highlighting the need for sensitive tumors and rational combination strategies to enhance their therapeutic potential. Here, we identified colon cancer-specific super-enhancers that were associated with multiple oncogenic pathways, including the mitogen-activated protein kinase (MAPK) signaling pathway. Among the 14 colon cancer cell lines tested, their sensitivity to JQ1, a BET inhibitor, was not correlated with c-MYC expression. Three of four BRAFV600E-mutant cell lines were sensitive. Addition of JQ1 to vemurafenib, a specific mutant BRAF inhibitor, suppressed cell growth by arresting cell cycle progression and inducing apoptosis in the BRAFV600E-mutant cells. Mechanistically, the feedback activation of MAPK signaling pathway by vemurafenib was repressed by JQ1. Further, the addition of JQ1 to a BRAF inhibitor enhanced the in vivo anti-tumor effect. Thus, this study indicates the therapeutic potential of targeting of super-enhancers and mutant BRAF in patients with BRAFV600E-mutant colorectal cancer.

[Purpose] To clarify factors contributing to habituation of pelvic floor muscle training (PFMT) for urinary incontinence. [Subjects and Methods] We included 13 healthy females and examined diurnal and nocturnal urination frequency at initial program participation and at 3 months. The survey used the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), a 10-level self-assessment of anxiety associated with urinary incontinence, and a 10-level self-evaluation of PFMT understanding and skill acquisition. We evaluated PFMT practice at home and postures that facilitated PFMT. The practice of PFMT at home was surveyed during a 3-month period. [Results] Compared to baseline, the level of skill acquisition assessed by the ICIQ-SF and PFMT according to the 10-level self-evaluation improved significantly at 3 months. The rate of PFMT sessions performed at home per week was high. The number of times PFMT was performed per day was positively correlated with level of understanding and acquisition of skills pertaining to PFMT, according to the 10-level self-assessment. [Conclusion] By incorporating behavior modification techniques appropriate for urinary incontinence and by increasing the level of understanding regarding incontinence and PFMT, as well as the level of skill acquisition, self-efficacy increased. This may have motivated habituation of PFMT.

In this study, impact of a polymorphism of CYP2C19 on drug–drug interaction (DDI) was examined for etizolam. The effect of itraconazole (a strong CYP3A inhibitor) on the pharmacokinetics of etizolam (a substrate of CYP2C19 and CYP3A) was assessed in both extensive metabolizers (EMs) and poor metabolizers (PMs) of CYP2C19. Sixteen participants (8 EMs and 8 PMs) received a single oral dose of etizolam (0.25 mg) on day 1. The participants ingested itraconazole (200 mg twice a day) on days 2–5. On day 5, participants received an oral dose of etizolam (0.25 mg) again. Before coadministration of itraconazole (day 1), the area under the time–plasma concentration curve from time zero to infinity (AUC∞) of etizolam was higher in PMs than in EMs (2.65-fold, P

[Purpose] The objective of this study was to clarify the effects of increased number of steps on body composition, physical functions, vascular functions, health-related quality of life (HR-QOL) and self-efficacy in elderly people. [Subjects and Methods] The subjects were 47 elderly persons who resided in Port Island in the Chuo Ward of Kobe City in Hyogo Prefecture, Japan. After the calculation of the mean preintervention physical activity (PA), the subjects were instructed to increase their PA to a target baseline + 1,300 steps/day. Body composition, physical functions, vascular functions, HR-QOL, and self-efficacy were measured at baseline, after 3 and 6 months. These items were compared between a group that increased their PA and a group that did not. [Results] After 6 months, 26.1% of the subjects achieved the PA target. No significant improvements were observed in body composition, physical functions, vascular functions, or self-efficacy for either group after 3 and 6 months. However, the HR-QOL improved significantly after 6 months in the achievement group. [Conclusion] Although the intervention to increase PA did not produce significant improvements after 6 months in body composition, physical functions, vascular functions, or self-efficacy, the HR-QOL improved significantly during this relatively short period.

Plants possess disease resistance (R) proteins encoded by R genes, and each R protein recognizes a specific pathogen factor(s) for immunity. Interestingly, a remarkably high degree of polymorphisms in R genes, which are traces of past mutation events during evolution, suggest the rapid diversification of R genes. However, little is known about molecular aspects that facilitate the rapid change of R genes because of the lack of tools that enable us to monitor de novo R gene mutations efficiently in an experimentally feasible time scale, especially in living plants. Here we introduce a model assay system that enables efficient in planta detection of de novo mutation events in the Arabidopsis thaliana R gene UNI in one generation. The uni-1D mutant harbors a gain-of-function allele of the UNI gene. uni-1D heterozygous individuals originally exhibit dwarfism with abnormally short stems. However, interestingly, morphologically normal stems sometimes emerge spontaneously from the uni-1D plants, and the morphologically reverted tissues carry additional de novo mutations in the UNI gene. Strikingly, under an extreme condition, almost half of the examined population shows the reversion phenomenon. By taking advantage of this phenomenon, we demonstrate that the reversion frequency is remarkably sensitive to a variety of fluctuations in DNA stability, underlying a mutable tendency of the UNI gene. We also reveal that activities of the salicylic acid pathway and DNA damage sensor pathway are involved in the reversion phenomenon. Thus, we provide an experimentally feasible model tool to explore factors and conditions that significantly affect the R gene mutation phenomenon.

The "Skippu-Mama" peer support program was developed to improve quality of life and reduce parental stress in mothers of children with autism spectrum disorders. The program was designed to improve these variables by refreshing and healing participants' minds and bodies. Twenty-four mothers of 26 children diagnosed with ASD in Japan were included in the study and completed measures of quality of life and parental stress before, during, and after participation in the Skippu-Mama program. Our results demonstrated that time was a significant main effect. Further, multiple comparisons with Bonferroni corrections indicated a significant increase in World Health Organization Quality of Life 26 scores three months into the program and at its conclusion six months after commencement. Overall, the Skippu-Mama program improved the quality of life of mothers of children with ASD, and we believe that the intervention's focus on both individual and family variables may be especially effective in this population.