Direct Parental (DIPA) CRISPR in the jewel wasp, Nasonia vitripennis.

While CRISPR-Cas9 technology has demonstrated remarkable promise as a gene editing tool, its application in certain insects, such as the jewel wasp, Nasonia vitripennis, has been hindered by a lack of a tractable method for reagent delivery. Direct Parental-CRISPR (DIPA-CRISPR) recently emerged as a facile way to induce gene lesions because it involves adult injection with commercially available Cas9-sgRNA with no helper reagent. However, DIPA-CRISPR has so far been tested in only a few insects. Here, we have assessed the viability of DIPA-CRISPR in N. vitripennis by targeting two eye-pigmentation genes, cinnabar and vermilion, which function in the ommochrome pathway. Successful generation of lesions in both genes demonstrated the functionality of DIPA-CRISPR in N. vitripennis and its potential application to other genes, thereby expanding the range of insects suitable for this method. We varied two parameters, Cas9-sgRNA concentration and injection volume, to determine optimal injection conditions. We found that the larger injection volume coupled with either higher or lower concentration was needed for consistent mutation production. However, DIPA-CRISPR yields an overall low mutation rate in N. vitripennis when compared to other tested insects, a characteristic that may be attributed to a proportionally low vitellogenic import efficiency in the jewel wasp. We discuss different factors that may be considered in determining when DIPA-CRISPR may be preferable over other reagent delivery methods.

Late Recurrence of Renal Cell Carcinoma in Unusual Sites 23 Years After Nephrectomy.

Renal cell carcinoma (RCC) is a common malignancy in the elderly population and it is notorious for its mechanism of late metastasis to unusual anatomical sites. Late recurrences are common following curative treatment, such as radical nephrectomy. Pancreatic metastases and hepatic metastatic lesions make the diagnosis and classification of a primary tumor challenging. This necessitates a high index of suspicion and an extensive interrogation. We present the case of a 68-year-old Hispanic female with progressive pain in the right upper quadrant, weight loss, and decreased appetite. She has a history of renal cell carcinoma treated with radical nephrectomy and radiotherapy. A pancreatic biopsy was performed based on the ultrasound and computed tomography findings at a private clinic. Subsequently, the patient was referred to the Instituto Oncologico Nacional (ION) due to immunohistochemical features suggestive of a well-differentiated neuroendocrine tumor. At ION, a more comprehensive medical history was obtained, and the immunohistochemistry panel was extended, confirming the diagnosis of late recurrence of RCC. One possible explanation for the very late relapse of our patient is the presence of malignant cells that were spared or seeded during the surgical intervention and remained dormant or latent, subsequently spreading via hematogenous dissemination or via the lymphatic system. We highlight the importance of medical history, pathological examination, and immunohistochemical analysis in establishing a differential diagnosis, given the nature of RCC, which can often present asymptomatically and has a propensity for late recurrence. Further research should focus on developing standardized surveillance protocols for such cases.

Optimizing ATTAIN implementation in a federally qualified health center guided by the FRAME-IS.

Implementation strategies are methods or techniques used to adopt, implement, and sustain evidence-based practices (EBPs). Implementation strategies are dynamic and may require adaptation to fit implementation contexts, especially in low-resource settings, which are most likely to serve racially and ethnically diverse patients. The framework for reporting adaptations and modifications to evidence-based implementation strategies (FRAME-IS) was used to document adaptations to implementation strategies to inform an optimization pilot of Access to Tailored Autism Integrated Care (ATTAIN; an integrated care model for children with autism and co-occurring mental health needs) in a federally qualified health center (FQHC) near the United States/Mexico border. Quantitative and qualitative data were collected from 36 primary care providers who participated in the initial ATTAIN feasibility pilot to inform adaptations. Adaptations were mapped to the FRAME-IS through an iterative template analysis to inform an optimization pilot at a FQHC 1-year from the start of the COVID-19 pandemic. Four implementation strategies (training and workflow reminders, provider/clinic champions, periodic reflections, and technical assistance) were employed during the feasibility pilot and were adapted for the optimization pilot to fit the needs of the FQHC and service delivery changes prompted by the pandemic. Findings demonstrate the utility of using the FRAME-IS to systematically inform EBP optimization in a FQHC providing care to underserved communities. Findings will inform future research studies implementing integrated mental health models in low-resourced primary care settings. Implementation outcomes and provider perceptions of ATTAIN at the FQHC are also reported. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Psychometric Assessment of the Eyberg Child Behavior Inventory in Children with Autism in Community Settings.

The Eyberg Child Behavior Inventory (ECBI) is a frequently used measure to assess interfering behaviors in children and psychometric properties have recently been examined in children with autism spectrum disorder (ASD). There is a need to confirm the identified factors and examine the factor structure in a racially/ethnically diverse, community-based sample. The current study conducts a psychometric analysis of the ECBI in a sample of children with ASD receiving publicly-funded mental health services. Data were collected from 201 children with ASD ages 5-13 years (60% Hispanic/Latinx) participating in a community effectiveness trial. Confirmatory factor analysis indicated poor model fit using previously identified factors and a new four-factor solution was identified. Clinical and research implications of these findings are discussed.

Caregiver Insights and Improvement Strategies for Youth with Autism Undergoing Gastrointestinal Endoscopy.

Limited guidance is available for families of youth with ASD (YASD) to prepare for invasive medical procedures. This study examined caregiver perspectives regarding YASD's gastrointestinal endoscopy (GE) experience to improve the endoscopy experience for YASD. Thirty-four caregivers of YASD, (M = 9.85 years, SD = 4.6) who underwent GE at Rady Children's Hospital, San Diego between May 2018 and July 2019 (identified via electronic health record) participated in a structured phone interview. Caregivers reported a positive experience due to the procedural team's responsiveness to the needs of YASD and appropriately answering/addressing questions/concerns. Caregivers reported a need for ASD-specific information on how to prepare for GE. Specific recommendations are discussed. Study findings offer strategies to improve the care experience of YASD undergoing GE.

A Single Amino Acid Substitution in Porcine Reproductive and Respiratory Syndrome Virus Glycoprotein 2 Significantly Impairs Its Infectivity in Macrophages.

Porcine reproductive and respiratory syndrome virus (PRRSV) has a restricted tropism for macrophages and CD163 is a key receptor for infection. In this study, the PRRSV strain NCV1 was passaged on MARC-145 cells for 95 passages, and two plaque-clones (C1 and C2) were randomly selected for further analysis. The C1 virus nearly lost the ability to infect porcine alveolar macrophages (PAMs), as well as porcine kidney cells expressing porcine CD163 (PK15-pCD163), while the C2 virus replicates well in these two cell types. Pretreatment of MARC-145 cells with an anti-CD163 antibody nearly blocked C1 virus infection, indicating that the virus still required CD163 to infect cells. The C1 virus carried four unique amino acid substitutions: three in the nonstructural proteins and a K160I in GP2. The introduction of an I160K substitution in GP2 of the C1 virus restored its infectivity in PAMs and PK15-pCD163 cells, while the introduction of a K160I substitution in GP2 of the low-passaged, virulent PRRSV strain NCV13 significantly impaired its infectivity. Importantly, pigs inoculated with the rNCV13-K160I mutant exhibited lower viremia levels and lung lesions than those infected with the parental rNCV13. These results demonstrated that the K160 residue in GP2 is one of the key determinants of PRRSV tropism.

Training Community Therapists in AIM HI: Individual Family and Neighborhood Factors and Child/Caregiver Outcomes.

OBJECTIVE: Publicly funded mental health services play an important role in caring for children with mental health needs, including children with autism spectrum disorder (ASD). This study assessed the associations between individual family- and neighborhood-level sociodemographic factors and baseline family functioning and long-term outcomes when community therapists were trained to deliver An Individualized Mental Health Intervention for ASD (AIM HI). METHOD: Participants included 144 children with ASD (ages 5 to 13 years; 58.3% Latinx) and their caregivers whose therapists received AIM HI training within a cluster-randomized effectiveness-implementation trial in publicly funded mental health services. Sociodemographic strain (e.g., low income, less education, single-parent status, minoritized status) was coded at the individual family and neighborhood level, and caregivers rated caregiver strain at baseline. Child interfering behaviors and caregiver sense of competence were assessed at baseline and 6-, 12- and 18-months after baseline. RESULTS: Higher caregiver strain was associated with higher intensity of child behaviors (B = 5.17, p < .001) and lower caregiver sense of competence (B = -6.59, p < 001) at baseline. Child and caregiver outcomes improved over time. Higher caregiver strain (B = 1.50, p < .001) and lower family sociodemographic strain (B = -0.58, p < .01) were associated with less improvements in child behaviors. Lower caregiver strain (B = -2.08, p < .001) and lower neighborhood sociodemographic strain (B = -0.51, p < .01) were associated with greater improvements in caregiver sense of competence. CONCLUSIONS: Findings corroborate the importance of considering both family and neighborhood context in the community delivery of child-focused EBIs. TRIAL REGISTRATION: Clinical Trials NCT02416323.

Pre-Implementation Organizational Environment Associated with Pediatric Integrated Care Readiness in Primary Care.

Objective: To characterize pre-implementation organizational factors associated with Access To Tailored Autism Integrated Care (ATTAIN), an integrated care model for children with autism and identified or suspected co-occurring mental health needs. Methods: Pediatric primary care providers (n=36) completed surveys as part of a pilot study testing ATTAIN feasibility. Measures assessed: background characteristics; implementation climate; organizational readiness; evidence-based practice (EBP) attitudes; knowledge, confidence and comfort caring for children with autism. Results: Compared to providers from a network of primary care practices and an integrated healthcare system, providers from a Federally Qualified Health Center (FQHC) reported less positive perceptions of climate supportive of EBP implementation and, specifically, selection for openness and rewards for EBPs. Implementation climate was associated with autism knowledge, comfort with mental health referral and follow up, and organizational change efficacy. Conclusions: Findings advance understanding of pre-implementation organizational context factors important to assess for EBP implementation in diverse pediatric care settings.

EFFECTS OF TRICAINE METHANESULFONATE IN A MANAGED COLLECTION OF MOON JELLYFISH (AURELIA AURITA).

The moon jellyfish (Aurelia aurita) is a scyphozoan frequently maintained in public and private aquaria. Little research has been conducted to investigate the effects of various drugs, such as anesthetics, in this species. Tricaine methanesulfonate (MS-222), a common immersion anesthetic for fish and amphibians, was evaluated in a managed population of moon jellyfish. Twenty-four clinically healthy jellyfish were assigned into three groups of eight for trials of 0.3 g/L MS-222 (low concentration [LC]), 0.6 g/L MS-222 (high concentration [HC]), and a saltwater control. The goal was to evaluate the effects of MS-222 administration on moon jellyfish movement and response to stimuli. Movement and response to stimuli were measured via rocking and probe stimulus tests and observations of bell contraction quality and body tone. These tests were performed at baseline and throughout both drug exposure and recovery periods. A threshold drug effect was defined based on systematic scoring criteria. Additionally, elastomer tags were administered to four of eight animals in each MS-222 group to evaluate response to tag placement after drug exposure. Threshold drug effect was achieved in six of eight individuals in the LC group and eight of eight individuals in the HC group. The LC group had median threshold and recovery times of 12.2 and 10.1 min, respectively, while the HC group had median threshold and recovery times of 4.0 and 19.9 min, respectively. The HC group had significantly faster time to threshold drug effect (P < 0.001) and longer recovery times (P= 0.005) than the LC group. In both the LC and HC tagged group, three of four jellyfish had no reaction to tag placement. All animals recovered uneventfully, and there were no mortalities. MS-222 at 0.3 and 0.6 g/L decreased movement and response to stimuli in moon jellyfish.

Mental health screening in pediatric primary care for children with autism.

LAY ABSTRACT: Children with autism experience high rates of co-occurring mental health conditions like challenging behaviors and anxiety. However, these co-occurring mental health needs are often not identified when they first become problematic. Pediatricians and their care staff are in a good position to identify mental health needs early and support families to connect to needed services. This study describes a project focused on mental health screening for children with autism in pediatric primary care clinics. Over half of eligible patients were screened using the Pediatric Symptom Checklist-17. Many children with autism had clinically elevated scores, suggesting the need for mental health assessment or services. In particular, children with positive screens had clinical elevations on the challenging behavior and attention subscales of the Pediatric Symptom Checklist-17. This finding is consistent with typical trends in co-occurring challenging behavior presentations in children with autism. Mental health screening in primary care is feasible and offers a promising opportunity to identify co-occurring mental health needs for children with autism early. Screening rates varied between clinics, suggesting tailored to improve routine screening in pediatric primary care for children with autism.

Implementation outcomes from a pilot of "Access to Tailored Autism Integrated Care" for children with autism and mental health needs.

LAY ABSTRACT: Children with autism frequently experience co-occurring mental health needs. The "Access to Tailored Autism Integrated Care (ATTAIN)" model was co-created with caregivers, pediatric providers, and health care leaders to identify mental health needs and link to mental health care for autistic children. This article describes outcomes from a pilot study of Access to Tailored Autism Integrated Care with 36 pediatric primary care providers from seven clinics within three healthcare systems. Providers participated in an initial Access to Tailored Autism Integrated Care training and received ongoing online support over 4 months with autistic patients ages 4-16 years old. Survey and interview assessments measured provider perceptions of feasibility, acceptability, and intentions to continue using Access to Tailored Autism Integrated Care after the pilot. Providers reported that Access to Tailored Autism Integrated Care was feasible, acceptable, that the initial training was helpful in their implementation but that more specific and tailored implementation support was needed. Results show that Access to Tailored Autism Integrated Care is a promising model to support mental health screening and linkage for children with autism in primary care. Findings provide information on specific areas of the Access to Tailored Autism Integrated Care model that could be benefit from additional refinement to support more widespread use in primary care settings.

Longitudinal Profiling of the Macaque Vaginal Microbiome Reveals Similarities to Diverse Human Vaginal Communities.

The vaginal microbiota plays an important role in women's reproductive and urogenital health. It is now well accepted that a "healthy" vaginal microbiome is dominated by Lactobacillus species. Disturbances in this microbial community can lead to several adverse outcomes, including pelvic inflammatory disease and bacterial vaginosis (BV), as well as increased susceptibility to sexually transmitted infections, miscarriage, and preterm births. However, vaginal communities, especially those of women in the developing world, can be comprised of a diverse set of microorganisms in the absence of overt clinical symptoms. The implications of these diverse vaginal microbiomes for women's health remain poorly understood. Rhesus macaques are an excellent translational animal model to address these questions due to significant physiological and genetic homology with humans. In this study, we performed a longitudinal analysis of clinical and microbiome data from 16 reproductive-age female rhesus macaques. At both the taxonomic and functional levels, the rhesus macaque vaginal microbiome was most similar to that of women who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Specifically, rhesus macaque vaginal microbiomes harbored a diverse set of anaerobic Gram-negative bacteria, including Sneathia, Prevotella, Porphyromonas, and Mobiluncus Interestingly, some animals were transiently colonized by Lactobacillus and some with Gardnerella Our in-depth and comprehensive analysis highlights the importance of the model to understand the health implications of a diverse vaginal microbiome and test interventions for manipulating this community.IMPORTANCE It is widely accepted that the "healthy" vaginal microbiome of women in the developed world is dominated by Lactobacillus species. However, in the developing world, many asymptomatic women harbor diverse vaginal microbial communities that are typically associated with bacterial vaginosis. Many questions remain about the drivers and health implications of a diverse vaginal microbial community. Rhesus macaques provide an excellent translational model to address these questions due to significant physiological and genetic homology with humans. In this study, we performed a longitudinal analysis of clinical and microbiome data from a large cohort of reproductive-age rhesus macaques. At the taxonomic, genomic, and functional levels, the rhesus macaque vaginal microbiome was most similar to that of humans, who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Our in-depth and comprehensive analysis highlights the utility of macaques as a model to study diverse vaginal community state types and test interventions for manipulating the vaginal microbiome.

Characterizing therapist delivery of evidence-based intervention strategies in publicly funded mental health services for children with autism spectrum disorder: Differentiating practice patterns in usual care and AIM HI delivery.

LAY ABSTRACT: This study was conducted to identify patterns of therapist delivery of evidence-based intervention strategies with children with autism spectrum disorder receiving publicly funded mental health services and compare strategy use for therapists delivering usual care to those trained to deliver AIM HI ("An Individualized Mental Health Intervention for ASD"), an intervention designed to reduce challenging behaviors in children with autism spectrum disorder. For therapists trained in AIM HI, intervention strategies grouped onto two factors, Autism Engagement Strategies and Active Teaching Strategies, while strategies used by usual care therapists grouped onto a broader single factor, General Strategies. Among usual care therapists, General Strategies were related to an increase in child behavior problems, whereas for AIM HI therapists, Active Teaching Strategies were related with reductions in child behavior problems over 18 months. Findings support the use of active teaching strategies in reducing challenging behaviors in children with autism spectrum disorder and provide support for the effectiveness of training therapists in evidence-based interventions to promote the delivery of targeted, specific intervention strategies to children with autism spectrum disorder in mental health services.

Training Community Therapists to Deliver an Individualized Mental Health Intervention for Autism Spectrum Disorder: Changes in Caregiver Outcomes and Mediating Role on Child Outcomes.

OBJECTIVE: This study examines the impact of training therapists to deliver "An Individualized Mental Health Intervention for Autism Spectrum Disorder (ASD)" (AIM HI) for children with autism spectrum disorder on caregiver outcomes and the mediating role of changes in caregiver outcomes on child outcomes. METHOD: Data were drawn from a cluster randomized trial conducted in 29 publicly funded mental health programs randomized to receive AIM HI training or usual care. Therapists were recruited from enrolled programs and child/caregiver participants enrolled from therapists' caseloads. Participants included 202 caregivers of children 5 to 13 years of age with autism spectrum disorder. Caregiver strain and sense of competence were assessed at baseline and 6 month postbaseline. Child behaviors were assessed at baseline and 6, 12, and 18 months postbaseline. Therapist delivery of evidence-based intervention strategies were assessed between baseline and 6 months. RESULTS: A significant training effect was observed for caregiver sense of competence, with AIM HI caregivers reporting significantly greater improvement relative to usual care. There was no significant training effect for caregiver strain. Observer-rated therapist delivery of evidence-based interventions strategies over 6 months mediated training effects for sense of competence at 6 months. Changes in sense of competence from baseline to 6 months was associated with reduced child challenging behaviors at 6 months and mediated child outcomes at 12 and 18 months. CONCLUSION: Combined with research demonstrating effectiveness of therapist AIM HI training on child outcomes, this study provides further evidence of the positive impact of training community therapists in the AIM HI intervention. CLINICAL TRIAL REGISTRATION INFORMATION: Effectiveness and Implementation of a Mental Health Intervention for ASD (AIM HI); https://clinicaltrials.gov/; NCT02416323.

Pediatric Primary Care Perspectives on Integrated Mental Health Care for Autism.

OBJECTIVE: Timely identification of mental health needs and linkage to services is critical to provide comprehensive care for children with autism spectrum disorder (ASD). Pediatric primary care is well-positioned to facilitate this process through integrated care approaches. As a first step toward mental health integration, this study applied the Exploration, Preparation, Implementation, and Sustainment framework to characterize determinants of implementing integrated care practices for ASD. METHODS: Sixty pediatric primary care providers and leaders from 3 organizations completed focus groups and surveys about identification of mental health needs in children with ASD and access to mental health services. Findings were integrated to examine convergence (ie, do the 2 methods confirm or find similar results) and expansion (ie, do the 2 methods provide insights beyond either method alone). RESULTS: Results converged regarding 3 primary influences to integrated care practices for ASD: 1) limited specialized mental health referral options for ASD, 2) unique structural characteristics of the mental health system act as barriers to accessing care, and 3) caregivers differ in the degree to which they understand co-occurring mental health conditions and pursue recommended services. Qualitative results provided expansion by highlighting unique implementation considerations (eg, alignment with health care delivery priorities and values) based on primary care characteristics. CONCLUSIONS: Findings confirm need for a tailored approach for linking children with ASD to appropriate mental health treatment. Results yield insight into the needs for organizational capacity to support integrated care and provide direction toward adapting an integrated mental health care model for children with ASD.

Measuring treatment response in children with autism spectrum disorder: Applications of the Brief Observation of Social Communication Change to the Autism Diagnostic Observation Schedule.

This study aims to determine the validity and reliability of applying the coding strategy from the Brief Observation of Social Communication Change, a newly validated treatment outcome measure, to videotaped segments of the Autism Diagnostic Observation Schedule. Results indicate strong reliability and validity of the Brief Observation of Social Communication Change ratings using the Autism Diagnostic Observation Schedule segments in detecting changes in social communication over the course of treatment in young, minimally verbal children with autism spectrum disorder. Results also suggest that the Brief Observation of Social Communication Change, when applied to Autism Diagnostic Observation Schedule segments, may be more sensitive in detecting subtle changes in social communication compared to the Autism Diagnostic Observation Schedule Calibrated Severity Scores. These results may support the application of the Brief Observation of Social Communication Change to pre-existing datasets of Autism Diagnostic Observation Schedule videos to examine treatment responses.

Response to Distress Varies by Social Impairment and Familiarity in Infants at Risk for Autism.

Early impaired response to social partners' distress may negatively impact subsequent social development. Identifying factors contributing to successful responding may inform assessment and intervention. This study explores how: (1) social impairment, and (2) partner familiarity relate to response to partners' distress. Infants with and without older siblings with ASD were assessed at 12 (n = 29) and 15 (n = 35) months for social impairment markers, and responses to mother and experimenter each feigning distress. Infants with more social impairment showed less attention and affect at 15, but not 12 months. Infants attended more to the unfamiliar person, but exhibited greater affect toward the familiar person at 12 months. Results revealed social impairment and familiarity were separately related to infant response to partners' distress.

Glycemic control and the outcomes of Hispanic patients with diabetes admitted to the general ward of a community hospital in Puerto Rico.

OBJECTIVE: Uncontrolled glucose, present in 40% of diabetic patients admitted to United States hospitals, has been associated with prolonged length of stay and poorer general outcomes in critically ill and surgical patients. However, past studies of general ward patients have shown there to be no consistent benefits of strict glucose control, and the Hispanic population has been underrepresented in such studies. This work evaluated the association between glycemic control and the outcomes of hospitalized Hispanics with diabetes and to describe physicians' interventions in the treatment of diabetes. METHODS: This is a retrospective chart review of all patients with diabetes admitted over a period of six months in the general ward of a community hospital in Puerto Rico. We evaluated glucose levels during the first 72 hours, length of stay, and reported complications during admission. Outcomes were evaluated with crude odds ratios and multivariate logistic regression. RESULTS: Uncontrolled blood glucose was observed in 59.1% of the 875 patients whose records were revised; of that 59.1%, treatment modification was not prescribed for 43.2%. Patients with poorly controlled glucose were more likely to develop acute coronary syndrome (corrected OR: 11.46; 95% CI = 1.48-88.50) as a complication and less likely to develop hypoglycemia (corrected OR: 0.57; 95% = CI 0.37-0.88). CONCLUSION: Our results suggest that hospitalized but non-critically ill Hispanic patients with diabetes are prone to poor outcomes secondary to uncontrolled glucose levels; in addition, those results support the creation of standardized protocols for the management of diabetes in this population.