Numb positively regulates Hedgehog signaling at the ciliary pocket.

Hedgehog (Hh) signaling relies on the primary cilium, a cell surface organelle that serves as a signaling hub for the cell. Using proximity labeling and quantitative proteomics, we identify Numb as a ciliary protein that positively regulates Hh signaling. Numb localizes to the ciliary pocket and acts as an endocytic adaptor to incorporate Ptch1 into clathrin-coated vesicles, thereby promoting Ptch1 exit from the cilium, a key step in Hh signaling activation. Numb loss impedes Sonic hedgehog (Shh)-induced Ptch1 exit from the cilium, resulting in reduced Hh signaling. Numb loss in spinal neural progenitors reduces Shh-induced differentiation into cell fates reliant on high Hh activity. Genetic ablation of Numb in the developing cerebellum impairs the proliferation of granule cell precursors, a Hh-dependent process, resulting in reduced cerebellar size. This study highlights Numb as a regulator of ciliary Ptch1 levels during Hh signal activation and demonstrates the key role of ciliary pocket-mediated endocytosis in cell signaling.

Benefits and concerns of expanded carrier screening: what do pregnant Latina women in Texas think?

The American College of Medical Genetics and Genomics (ACMG) recommends carrier screening for all pregnant women regardless of race or ethnicity. In recent years, the ACMG broadened the guidelines to include expanded carrier screening (ECS) which can screen for 112 conditions. This study seeks to explore the perceptions of pregnant Latina women about the benefits and concerns related to ECS use. Partnering with prenatal clinics in Texas, we conducted semi-structured qualitative interviews with 32 pregnant Latina women in their second or third trimester of pregnancy. NVivo 8 was used to conduct content analysis and emergent coding of the data. Participants reported the benefits of ECS as helping them prepare for the baby's arrival, informing them of the baby's risk for genetic conditions, ensuring the health of their baby, and preventing diseases before birth. The ECS-related concerns expressed by the participants included worries surrounding potential positive ECS results, insufficient knowledge about the genetic diseases screened for by ECS, the accuracy of the ECS, the potential harm ECS may cause the baby, and the affordability of ECS. After weighing both their perceived benefits and concerns, nearly all the participants believed that ECS should be offered to all pregnant women. This study contributes to an understudied research area in the genetic/genomic field. Our findings can help increase the awareness of obstetricians, genetic professionals, and other healthcare providers regarding pregnant Latina women's views on ECS and inform the design of culturally appropriate care as ECS is adopted into routine clinical practice.

Treatment Persistence and Medication Switch Associated With Subsequent Fractures After Osteoporotic Fractures.

CONTEXT: Despite prevalent anti-osteoporosis medication (AOM) switching in real-world osteoporosis management, few studies have evaluated the impact of persistent AOM treatment, allowing for AOM switching, on the risk of subsequent fracture. OBJECTIVE: We examined the association between persistence in AOM and subsequent fractures, allowing for medication switching among patients with osteoporotic fractures. METHODS: This retrospective cohort study used Taiwan National Health Insurance claims data to select patients who initiated AOM between 2013 and 2016. Treatment persistence was defined as use of any AOM on a given day of interest with a 45-day grace period. Medication switch was allowed for persistence if remaining on treatment. AOMs with long-lasting inhibition of bone resorption (zoledronate and denosumab) were categorized as high-potency; others as low-potency. Multivariate Cox models were used to evaluate risk of subsequent fractures ≥3 months after initiating AOM. RESULTS: A total of 119 473 patients were included (mean [SD] follow-up 46.4 [15.6] months), and 26.8% switched from the index AOM. Within 1 year, 52% remained persistent with AOM. Compared to patients with persistent AOM, those not persistent had higher risk of subsequent hip (adjusted hazard ratio [aHR] = 1.31; 95% CI, 1.21-1.42), vertebral (aHR = 1.17; 95% CI, 1.13-1.22), and radius fractures (aHR = 1.16; 95% CI, 1.08-1.25). Patients with persistent AOM who switched from high- to low-potency AOM had higher risk of subsequent vertebral fractures than those with persistent AOM and no potency switch (aHR = 1.28; 95% CI, 1.02-1.60). CONCLUSION: Patients with non-persistent AOM had higher risk of subsequent fractures than persistent users when allowing AOM switch. Switching AOM potency may influence the risk of subsequent vertebral fractures and warrants further investigation.

Higher risk of future events, mortality and greater healthcare use among patients with increasingly recurrent atherosclerotic cardiovascular disease events in Taiwan: a retrospective cohort study.

OBJECTIVES: To describe the occurrence of recurrent atherosclerotic cardiovascular disease (ASCVD) events within 3 years after a new-onset event, the associated disease burden and statin prescribing in patients with ASCVD in Taiwan. DESIGN: Retrospective cohort study. SETTING: This was a retrospective cohort study using Taiwan's National Health Insurance Research Database. PARTICIPANTS: In total, 111 399, 133 538 and 21 572 patients who were hospitalised with diagnosis of coronary heart disease (CHD), cerebrovascular disease (CBVD) and peripheral artery disease (PAD), respectively, between 1 January 2012 and 31 December 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: For each index and recurrent event, patients were observed for 12 months after admission to quantify risks of mortality, recurrent events, statin treatment and healthcare use. RESULTS: We identified 97 321, 120 914 and 14 794 patients with new-onset CHD, CBVD and PAD, respectively. The proportions of developing first, second and third recurrent events were 22.5%, 25.6% and 30.9% for CHD; 20.9%, 26.2% and 32.4% for CBVD and 40.2%, 41.4% and 43.6% for PAD, respectively. Most patients had the same type of ASCVD for their recurrent events as their new-onset event. The mortality rates increased with each recurrent event (p<0.05 for all three ASCVD groups). The rates of hospital readmission and emergency room (ER) visit increased with increasing recurrent events. For example, in the CHD group, the 1-year readmission rates following the index, first and second recurrent events were 43.1%, 47.6% and 55.3%, respectively, and the proportions of visiting ER were 46.4%, 51.9% and 57.8%, respectively. Statin prescribing was suboptimal at time of index event and recurrent events. CONCLUSION: Recurrent ASCVD events were associated with a higher risk of recurrent event and mortality and greater healthcare use. However, statin prescriptions at index event and after each recurrent event were suboptimal.

Identification of thrombotic biomarkers in orthopedic surgery patients by plasma proteomics.

BACKGROUND: Due to the poor specificity of D-dimer, more accurate thrombus biomarkers are clinically needed to improve the diagnostic power of VTE. METHODS: The plasma samples were classified into low-risk group (n = 6) and high-risk group (n = 6) according to the Caprini Thrombosis Risk Assessment Scale score. Data-independent acquisition mass spectrometry (DIA-MS) was performed to identify the proteins in the 12 plasma samples. Bioinformatics analysis including volcano plot, heatmap, KEGG pathways and chord diagram analysis were drawn to analyze the significantly differentially expressed proteins (DEPs) between the two groups. Then, another 26 plasma samples were collected to verify the key proteins as potential biomarkers of VTE in orthopedic surgery patients. RESULTS: A total of 371 proteins were identified by DIA-MS in 12 plasma samples. Volcano plotting showed that there were 30 DEPs. KEGG pathway enrichment analysis revealed that the DEPs were majorly involved in the blood coagulation pathway. The chord diagram analysis demonstrated that proteins SAA1, VWF, FLNA, ACTB, VINC, F13B, F13A and IPSP in the DEPs were significantly related to blood coagulation. VWF and F13B were selected for validation experiments. ELISA test showed that, as compared with those in the low-risk group, the level of VWF in the high-risk sera was significantly increased. CONCLUSIONS: The level of VWF in the high-risk group of thrombosis after orthopedic surgery was significantly higher than that in the low-risk group of preoperative thrombosis, suggesting that VWF may be used as a potential thrombus biomarker in orthopedic surgery patients.

Pregnant Latinas' perspectives on pursuing expanded carrier screening: "It is better to know than not".

With the advance of genetic technologies, the use of expanded carrier screening (ECS) in the prenatal setting is growing. ECS tests for a wide range of inherited genetic disorders regardless of racial/ethnic background and family history. Latinxs are an important ECS stakeholder group as they are the largest minority group with the highest fertility rate in the United States. Yet, the Latinx population has, to date, been underrepresented and understudied in genetics/genomics research. We conducted a study to explore the knowledge and perspectives of pregnant Latinas regarding ECS in which descriptive statistics and content analysis were used to analyze the data. Thirty-two pregnant Latinas - mostly of low educational levels (no education beyond high school) and with less than $20,000 annual household income living in rural areas were surveyed, provided with education about ECS, and interviewed. Participants were found to possess limited knowledge about ECS prior to being interviewed. Most (68.8%), however, expressed interest in pursuing ECS following the educational component that explained ECS. Their interest was mainly driven by the desire to know their baby's chance of developing a genetic disorder, the low risk of ECS procedures for both pregnant Latinas and their fetus, and the opportunity to better prepare for raising a child with a genetic condition. Our findings contribute to the limited research in the genetics/genomics field by providing in-depth insights into the perspectives of pregnant Latinas regarding ECS. Obstetric providers and genetic counselors should provide culturally appropriate education and counseling to empower pregnant Latinas to make informed decisions about the use of ECS.

Evaluation of a mandatory theory-based physical activity course on motivation among predominantly Hispanic college students.

ObjectiveThe present study aims to examine the impacts of a mandatory physical activity (PA) course on exercise motivation among predominately Hispanic college students. The course was designed based on the Self-Determination Theory to increase students' PA motivation. Methods: A total of 383 college students (nmales=126; nfemales=257; Mage=19.6; 67.6% Hispanic/Latino[a]) participated in the course and completed the Behavioral Regulation to Exercise Questionnaire-2 at the beginning (pretest) and the end of the course (post-test). This questionnaire measured five motivation constructs: amotivation, intrinsic motivation, extrinsic motivation, introjected regulation, and identified regulation. Results: Findings showed significant increases from pretest to post-test in all five motivation constructs (ps < 0.01). Conclusions: Although the mandatory PA curriculum successfully increased the intrinsic motivation, extrinsic motivation, introjected regulation, and identified regulation among college students, amotivation was also increased. These outcomes suggested some positive impacts on Hispanic college students' motivation to participate in PA. Findings can assist researchers and educators in developing, implementing, and evaluating required PA courses in colleges and universities.

Podocalyxin-Like Protein 1 Regulates Pluripotency through the Cholesterol Biosynthesis Pathway.

Deciphering signaling mechanisms critical for the extended pluripotent stem cell (EPSC) state and primed pluripotency is necessary for understanding embryonic development. Here, a membrane protein, podocalyxin-like protein 1 (PODXL) as being essential for extended and primed pluripotency, is identified. Alteration of PODXL expression levels affects self-renewal, protein expression of c-MYC and telomerase, and induced pluripotent stem cell (iPSC) and EPSC colony formation. PODXL is the first membrane protein reported to regulate de novo cholesterol biosynthesis, and human pluripotent stem cells (hPSCs) are more sensitive to cholesterol depletion than fibroblasts. The addition of exogenous cholesterol fully restores PODXL knockdown-mediated loss of pluripotency. PODXL affects lipid raft dynamics via the regulation of cholesterol. PODXL recruits the RAC1/CDC42/actin network to regulate SREBP1 and SREBP2 maturation and lipid raft dynamics. Single-cell RNA sequencing reveals PODXL overexpression enhanced chimerism between human cells in mouse host embryos (hEPSCs 57%). Interestingly, in the human-mouse chimeras, laminin and collagen signaling-related pathways are dominant in PODXL overexpressing cells. It is concluded that cholesterol regulation via PODXL signaling is critical for ESC/EPSC.

Treatment patterns of long-dose-interval medication for persistent management of osteoporosis in Taiwan.

Treatment persistence was higher among the patients who initially received an anti-osteoporosis medication (AOM) with a long-dose-interval. PURPOSE: With long-dose-interval anti-osteoporosis medications (AOMs) available for osteoporosis management, it is important to evaluate persistence of any AOM as long as it is continuously used. The purpose of this study was to investigate the treatment pattern and persistence of AOMs, allowing for medication switch. METHODS: This study was an observational retrospective cohort study using Taiwan's National Health Insurance claims data. We selected patients who first initiated an AOM between January 1, 2013, and June 30, 2016. AOM therapy included alendronate, raloxifene, teriparatide, denosumab, zoledronate, and ibandronate; the latter three were categorized as long-dose-interval medications. Persistence was defined as continual prescription of any AOM at a given time point with a grace period of 45 days within which to obtain prescription refill. The competing risk model was used to examine the factors affecting patients switching their initial AOM. RESULTS: During the study period, 126,539 patients with mean age of 75 years met the inclusion criteria; 85% were female. For initial AOM, 43.3%, 25.6%, 14.6%, 9.3%, 5.3%, and 1.9% of the patients received alendronate, denosumab, raloxifene, zoledronate, ibandronate, and teriparatide, respectively. During a mean 36-month follow-up, 29.6% of the patients who received at least two AOM pharmacy claims throughout the study period have ever switched their initial medication. Long-dose-interval medications, mainly denosumab and zoledronate, were the preferred choice for medication switch. Treatment persistence was higher in patients who initiated with long-dose-interval AOMs. CONCLUSION: The real-world data reveal long-dose-interval therapy as an initial treatment or at the first switch stage may improve management of persistent AOM treatment.

Development of a Chemical Cocktail That Rescues Mouse Brain Demyelination in a Cuprizone-Induced Model.

Oligodendrocytes are glial cells located in the central nervous system (CNS) that play essential roles in the transmission of nerve signals and in the neuroprotection of myelinated neurons. The dysfunction or loss of oligodendrocytes leads to demyelinating diseases such as multiple sclerosis (MS). To treat demyelinating diseases, the development of a therapy that promotes remyelination is required. In the present study, we established an in vitro method to convert human fibroblasts into induced oligodendrocyte-like cells (iOLCs) in 3 days. The induced cells displayed morphologies and molecular signatures similar to oligodendrocytes after treatment with valproic acid and exposure to the small molecules Y27632, SU9516, and forskolin (FSK). To pursue the development of a cell-free remyelination therapy in vivo, we used a cuprizone-induced demyelinated mouse model. The small molecules (Y27632, SU9516, and FSK) were directly injected into the demyelinated corpus callosum of the mouse brain. This combination of small molecules rescued the demyelination phenotype within two weeks as observed by light and electron microscopy. These results provide a foundation for exploring the development of a treatment for demyelinating diseases via regenerative medicine.

Effects of cardiovascular arousal on emotional experience.

Studies of arousal and emotion show that generalized physiological arousal can enhance emotional experience for a range of different emotions. Other research shows that different emotions may be associated with specific patterns of physiological reactivity. Together these findings suggest that while nonspecific autonomic activation can be sufficient in the generation of emotion, specific patterns of reactivity may appear once the emotion is established. This study aimed to test this hypothesis by examining the effects of generalized arousal on emotional experience, as well as the physiological responses associated with positive and negative emotions. One hundred and nine participants either sat or stood during the viewing of positive and negative film clips while emotion ratings and cardiorespiratory measures were taken. Those who stood during the videos reported greater levels of emotion than those who sat, indicating that generalized arousal due to standing heightened emotional experience. In addition, participants exhibited greater high-frequency heart rate variability and lower respiration rate during the negative video than the positive video, indicating that physiological reactivity differed between the positive and negative emotions. These results suggest that while patterns of physiological reactivity may be specific to individual emotions, nonspecific arousal is sufficient to enhance diverse emotions.

Knowledge and Attitudes toward Genetic Testing for Autism Spectrum Disorders among Parents of Affected Children in Taiwan.

The prevalence of autism spectrum disorders (ASD) in Taiwan has been increasing, and genetic testing for ASD has been available and provided to parents of children diagnosed with ASD in Taiwan. However, there is still limited understanding of Taiwanese parents' knowledge of and attitudes toward such testing. Therefore, the present study addressed this gap by assessing the attitudes toward as well as actual and perceived knowledge of ASD genetic testing among Taiwanese parents of children diagnosed with ASD. A sample of 443 parents of children with ASD recruited from 236 public schools in Taiwan completed a paper-and-pencil survey. Although parents generally held favorable attitudes toward ASD genetic testing, they had deficient knowledge of such test (with only a 31.4% average correct rate on the actual knowledge scale). Tailored health education materials should be developed to improve the knowledge of ASD genetic testing among parents with affected children in Taiwan.

Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells.

The developmental potential within pluripotent cells in the canonical model is restricted to embryonic tissues, whereas totipotent cells can differentiate into both embryonic and extraembryonic tissues. Currently, the ability to culture in vitro totipotent cells possessing molecular and functional features like those of an early embryo in vivo has been a challenge. Recently, it was reported that treatment with a single spliceosome inhibitor, pladienolide B (plaB), can successfully reprogram mouse pluripotent stem cells into totipotent blastomere-like cells (TBLCs) in vitro. The TBLCs exhibited totipotency transcriptionally and acquired expanded developmental potential with the ability to yield various embryonic and extraembryonic tissues that may be employed as novel mouse developmental cell models. However, it is disputed whether TBLCs are 'true' totipotent stem cells equivalent to in vivo two-cell stage embryos. To address this question, single-cell RNA sequencing was applied to TBLCs and cells from early mouse embryonic developmental stages and the data were integrated using canonical correlation analyses. Differential expression analyses were performed between TBLCs and multi-embryonic cell stages to identify differentially expressed genes. Remarkably, a subpopulation within the TBLCs population expressed a high level of the totipotent-related genes Zscan4s and displayed transcriptomic features similar to mouse two-cell stage embryonic cells. This study underscores the subtle differences between in vitro derived TBLCs and in vivo mouse early developmental cell stages at the single-cell transcriptomic level. Our study has identified a new experimental model for stem cell biology, namely 'cluster 3', as a subpopulation of TBLCs that can be molecularly defined as near totipotent cells.

Perceptions of Autism Spectrum Disorder (ASD) Etiology among Parents of Children with ASD.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and restricted or repetitive behaviors. Parental perceptions of the etiology of their child's ASD can affect provider-client relationships, bonding between parents and their children, and the prognosis, treatment, and management of children with ASD. Thus, this study sought to examine the perceptions of ASD etiology of parents of children with ASD. METHODS: Forty-two parents of children diagnosed with ASD were recruited across Texas. Semi-structured interviews were conducted individually. All interviews were recorded and later transcribed verbatim for content analysis utilizing NVivo 12.0 (QSR International, Doncaster, Australia). RESULTS: The content analysis identified the following themes regarding parental perceptions of ASD etiology: Genetic factors (40.5%), environmental factors (31.0%), problems that occurred during pregnancy or delivery (23.8%), vaccinations (16.7%), other health problems (7.1%), parental age at the time of pregnancy (4.8%), and spiritual or religious factors (2.4%). CONCLUSIONS: The parental perceptions of ASD etiology were diverse, but several views, such as vaccinations and spiritual or religious factors, were not based on scientific evidence. Health professionals and researchers can use these findings to develop and provide targeted education to parents who have children with ASD. Our findings also support policymakers in developing campaigns designed to increase parental ASD awareness and knowledge.

Psychometric Properties of the POAGTS: A Tool for Understanding Parents' Perceptions Regarding Autism Spectrum Disorder Genetic Testing.

Due to the increased prevalence of Autism Spectrum Disorder (ASD), more children with ASD may be referred for genetic testing. It is important to develop a tool to help parents consider the benefits and drawbacks of genetic testing for ASD before pursuing genetic testing for children with ASD. We developed the first theory-based survey-Perceptions of ASD Genetic Testing Survey (POAGTS), as a tool to assist healthcare providers to better understand parents' perceptions and concerns regarding ASD genetic testing. The psychometric properties of POAGTS were first pre-tested and then formally tested with 308 parents of children with ASD who had not decided whether to pursue genetic testing for their children diagnosed with ASD. Findings suggest that the eight scales of the POAGTS were psychometrically sound, and had acceptable data reliability and validity. Additional research with various samples, such as parents of children with ASD who belong to diverse racial/ethnic and socioeconomic groups, is warranted in the future to determine whether the POAGTS is applicable to these particular groups. Condensing and refining this tool to a shorter, more user-friendly version is also recommended for future research.

Plasminogen Activator Inhibitor-1 Secretion by Autophagy Contributes to Melanoma Resistance to Chemotherapy through Tumor Microenvironment Modulation.

Autophagy plays a crucial role in maintenance of cellular homeostasis via intracellular signaling pathways, lysosomal degradation of selective cargo and mediating protein secretion. Dysregulation of autophagy has been implicated in tumorigenesis, tumor progression, and resistance to therapy. However, the mechanism of autophagy-dependent secretion involved in the responsiveness to chemotherapy is poorly understood. In this study, we showed that mitoxantrone (MitoX), a chemotherapeutic agent used for treating various cancers but not melanoma, induced autophagy in melanoma cells in vitro and in vivo. We also found that plasminogen activator inhibitor (PAI)-1 secretion by MitoX-induced autophagy modulated the pro-tumoral microenvironment. Attenuation of PAI-1 activity using a specific inhibitor, tiplaxtinin (TPX), or by targeting the autophagy gene, Becn1, induced efficient antitumor immunity, thereby overcoming the resistance to MitoX in vivo. Of note, the therapeutic efficacy of TPX was abolished in MitoX-treated Becn1-defective tumors. Collectively, our results demonstrate that tumor autophagy-dependent PAI-1 secretion impairs the therapeutic efficacy of MitoX and highlight targeting of tumor autophagy or its secretory cargo, PAI-1, as a novel strategy to repurpose MitoX-based chemotherapy for melanoma treatment.

Effects of human immunodeficiency virus status on symptom severity in influenza-like illness in an otherwise healthy adult outpatient cohort.

The impact of HIV on influenza-like illness (ILI) has been incompletely described in the era of combination antiretroviral therapy, particularly in the post-H1N1 pandemic period. This analysis informs on ILI in an otherwise healthy, predominantly outpatient cohort of adults with HIV in the USA. From September 2010 to March 2015, this multisite observational cohort study enrolled otherwise healthy adults presenting to a participating US military medical center with ILI, a subset of whom were HIV positive. Demographics, clinical data, and self-reported symptom severity were ascertained, and enrollees completed a daily symptom diary for up to 10 days. 510 men were included in the analysis; 50 (9.8%) were HIV positive. Subjects with HIV were older and less likely to be on active duty. Rhinovirus and influenza A were the most commonly identified pathogens. Moderate-severe diarrhea (p<0.001) and fatigue (p=0.01) were more frequently reported by HIV-positive men. HIV positivity was associated with higher gastrointestinal scores, but not other measures of ILI symptom severity, after controlling for age, race, military status, and influenza season. Few were hospitalized. HIV-positive subjects had more influenza B (p=0.04) and were more likely to receive antivirals (32% vs 6%, p<0.01). Antiviral use was not significantly associated with symptom scores when accounting for potential confounders. In this predominantly outpatient cohort of adult men, HIV had minimal impact on ILI symptom severity. Despite similar illness severity, a higher percentage of subjects with HIV reported undergoing antiviral treatment for ILI, likely reflecting differences in prescribing practices.Trial registration number: NCT01021098.

Family Health History-Based Cancer Prevention Training for Community Health Workers.

Cancer is the second leading cause of death in the U.S. Utilizing family health history in cancer prevention holds promise in lessening the burden of cancer. Nevertheless, family health history is underutilized in public health and preventive medicine. Community health workers, also known as lay health educators, are ideal candidates to offer basic cancer family history-based education and services to the general public. The authors developed the first cancer family history-based genomics training program in cancer prevention tailored for community health workers. This paper details the development and pilot testing findings of the training. Specifically, a multidisciplinary research team of geneticists, genetic counselors, health educators, community health workers, and community health worker instructors developed a 7-module, 6-hour, bilingual (English and Spanish) cancer family history-based training focusing on cancer family history-based risk assessment, lifestyle recommendations, and genetic evaluation and testing. The curriculum was based on an integrated theoretical framework, the National Comprehensive Cancer Network guidelines, the community health worker core competencies, and the 4MAT instructional model. The Texas Department of State Health Services approved and certified the curriculum with 2 delivery formats: in-person/face-to-face workshops and online training. A total of 34 community health workers completed the pilot training in person (n=17) and online (n=17) in 2018 and 2019. Participating community health workers' knowledge, attitudes, self-efficacy, and intention in delivering basic cancer family history-based genomics education and services significantly increased on the immediate post-test measures compared with their pretest data. Positive ratings and feedback were also reported by the community health workers. Findings from this pilot study suggest that wider training is warranted for educating more community health workers in the U.S.

Pursuing genetic testing for children with autism spectrum disorders: What do parents think?

The American Academy of Pediatrics, the American College of Medical Genetics and Genomics, and the American Academy of Neurology recommend genetic testing, as a genetic evaluation tool, for children diagnosed with autism spectrum disorders (ASD). Despite the potential benefits, the utilization of genetic testing is low. We proposed an integrated theoretical framework to examine parents' intention and associated psychosocial factors in pursuing genetic testing for their children with ASD. Recruiting primarily from the Interactive Autism Network, a nationwide sample of 411 parents of children with ASD who had never pursued genetic testing for their children completed our theory-based online survey. Data were analyzed using structural equation modeling. About half of the parents were willing to pursue genetic testing for their children with ASD. Findings of the structural equation modeling suggested a good model fit between our integrated theoretical framework and survey data. Parents' intention was significantly and positively associated with their attitudes toward genetic testing, subjective norm, and self-efficacy in having their children tested. This study serves as an initial window to understand parental intention to pursue genetic testing for their children with ASD. Our findings can help physicians and genetic counselors understand, educate, counsel, and support parents' decision-making about having their children with ASD genetically tested. Furthermore, our study can also assist physicians and genetic counselors in developing theory- and evidence-based patient education materials to enhance genetic testing knowledge among parents of children with ASD.