Structural deviations of the posterior fossa and the cerebellum and their cognitive links in a neurodevelopmental deletion syndrome.

High-impact genetic variants associated with neurodevelopmental disorders provide biologically-defined entry points for mechanistic investigation. The 3q29 deletion (3q29Del) is one such variant, conferring a 40-100-fold increased risk for schizophrenia, as well as high risk for autism and intellectual disability. However, the mechanisms leading to neurodevelopmental disability remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in individuals with 3q29Del (N = 24) and neurotypical controls (N = 1608) using structural MRI. Given prior radiology reports of posterior fossa abnormalities in 3q29Del, we focused our investigation on the cerebellum and its tissue-types and lobules. Additionally, we compared the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del and controls and examined the association between neuroanatomical findings and quantitative traits to probe gene-brain-behavior relationships. 3q29Del participants had smaller cerebellar cortex volumes than controls, before and after correction for intracranial volume (ICV). An anterior-posterior gradient emerged in finer grained lobule-based and voxel-wise analyses. 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction and displayed elevated rates of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Cerebellar white matter and subregional gray matter volumes were associated with visual-perception and visual-motor integration skills as well as IQ, while cystic/cyst-like malformations yielded no behavioral link. In summary, we find that abnormal development of cerebellar structures may represent neuroimaging-based biomarkers of cognitive and sensorimotor function in 3q29Del, adding to the growing evidence identifying cerebellar pathology as an intersection point between syndromic and idiopathic forms of neurodevelopmental disabilities.

Clinicopathologic Characteristics of PANDAS in a Young Adult: A Case Report.

Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) is an acute onset or exacerbation of neuropsychiatric symptoms following a group A streptococcus infection. It is believed to be a result of autoimmune response to streptococcal infection, but there is insufficient evidence to fully support this theory. Although this disease is primarily thought to be a disease of childhood, it is reported to occur also in adults. PANDAS is a well-defined clinical entity, but the neuropathology of this condition has not been established yet. We describe the clinical course of a 26-year-old female diagnosed with PANDAS. She committed suicide and her brain was biobanked for further studies. We examined the banked tissue and performed special stains, immunohistochemical, and immunofluorescence analyses to characterize the neuropathology of this condition. Histology of the temporal lobes, hippocampus, and basal ganglia shows mild gliosis and Alzheimer's type II astrocytes. Acute hypoxic ischemic changes were noted in hippocampus CA1 and CA2 areas. Immunostaining shows increased parenchymal/perivascular GFAP staining and many vessels with mild increases in CD3-, CD4-, and CD25-stained lymphocytes in the basal ganglia. The findings suggest that CD4- and CD25-positive T cells might have an important role in understanding the neuroinflammation and pathogenesis of this condition. The case represents the first neuropathological evaluation report for PANDAS.

Musculoskeletal phenotypes in 3q29 deletion syndrome.

3q29 deletion syndrome (3q29del) is a rare genomic disorder caused by a 1.6 Mb deletion (hg19, chr3:195725000-197350000). 3q29del is associated with neurodevelopmental and psychiatric phenotypes, including an astonishing >40-fold increased risk for schizophrenia, but medical phenotypes are less well-described. We used the online 3q29 registry of 206 individuals (3q29deletion.org) to recruit 57 individuals with 3q29del (56.14% male) and requested information about musculoskeletal phenotypes with a custom questionnaire. 85.96% of participants with 3q29del reported at least one musculoskeletal phenotype. Congenital anomalies were most common (70.18%), with pes planus (40.35%), pectus excavatum (22.81%), and pectus carinatum (5.26%) significantly elevated relative to the pediatric general population. 49.12% of participants reported fatigue after 30 min or less of activity. Bone fractures (8.77%) were significantly elevated relative to the pediatric general population. Participants commonly report receiving medical care for musculoskeletal complaints (71.93%), indicating that these phenotypes impact quality of life for individuals with 3q29del. This is the most comprehensive description of musculoskeletal phenotypes in 3q29del to date, suggests ideas for clinical evaluation, and expands our understanding of the phenotypic spectrum of this syndrome.

A method for rapid flow-cytometric isolation of endothelial nuclei and RNA from archived frozen brain tissue.

Endothelial cells are important contributors to brain development, physiology, and disease. Although RNA sequencing has contributed to the understanding of brain endothelial cell diversity, bulk analysis and single-cell approaches have relied on fresh tissue digestion protocols for the isolation of single endothelial cells and flow cytometry-based sorting on surface markers or transgene expression. These approaches are limited in the analysis of the endothelium in human brain tissues, where fresh samples are difficult to obtain. Here, we developed an approach to examine endothelial RNA expression by using an endothelial-specific marker to isolate nuclei from abundant archived frozen brain tissues. We show that this approach rapidly and reliably extracts endothelial nuclei from frozen mouse brain samples, and importantly, from archived frozen human brain tissues. Furthermore, isolated RNA transcript levels are closely correlated with expression in whole cells from tissue digestion protocols and are enriched in endothelial markers and depleted of markers of other brain cell types. As high-quality RNA transcripts could be obtained from as few as 100 nuclei in archived frozen human brain tissues, we predict that this approach should be useful for both bulk analysis of endothelial RNA transcripts in human brain tissues as well as single-cell analysis of endothelial sub-populations.

The use of diagnostic patterns for interventional cytopathology during rapid on-site evaluation and final classification.

Pathologist-performed fine-needle aspiration, or interventional cytopathology, is a minimally invasive, highly accurate technique for sampling and diagnosing palpable lesions. Utilizing cytomorphologic patterns during rapid onsite evaluation (ROSE) and final classification is one of many strategies that an interventional cytopathologist can employ to simplify the diagnostic approach. Herein, we provide an overview of the salient cytomorphologic patterns encountered in common specimens obtained by the interventional cytopathologist, including major salivary glands, the thyroid gland, and superficial lymph nodes. The topics covered should provide a primer for those interested in utilizing a site-specific, pattern-based approach to cytopathologic evaluation. In summary, cytomorphologic patterns can be used during ROSE to establish adequacy, build a differential diagnosis, and to appropriately triage the specimen for additional investigation, such as microbiology cultures, a liquid-based preparation, a cell block preparation, flow cytometry, chemical analysis, or molecular diagnostic tests. Finally, this approach can be applied at the time of diagnosis to suggest additional ancillary studies, such as immunohistochemistry, and to inform accurate and definitive classification.

Deep phenotyping in 3q29 deletion syndrome: recommendations for clinical care.

PURPOSE: To understand the consequences of the 3q29 deletion on medical, neurodevelopmental, psychiatric, brain structural, and neurological sequalae by systematic evaluation of affected individuals. To develop evidence-based recommendations using these data for effective clinical care. METHODS: Thirty-two individuals with the 3q29 deletion were evaluated using a defined phenotyping protocol and standardized data collection instruments. RESULTS: Medical manifestations were varied and reported across nearly every organ system. The most severe manifestations were congenital heart defects (25%) and the most common were gastrointestinal symptoms (81%). Physical examination revealed a high proportion of musculoskeletal findings (81%). Neurodevelopmental phenotypes represent a significant burden and include intellectual disability (34%), autism spectrum disorder (38%), executive function deficits (46%), and graphomotor weakness (78%). Psychiatric illness manifests across the lifespan with psychosis prodrome (15%), psychosis (20%), anxiety disorders (40%), and attention deficit-hyperactivity disorder (ADHD) (63%). Neuroimaging revealed structural anomalies of the posterior fossa, but on neurological exam study subjects displayed only mild or moderate motor vulnerabilities. CONCLUSION: By direct evaluation of 3q29 deletion study subjects, we document common features of the syndrome, including a high burden of neurodevelopmental and neuropsychiatric phenotypes. Evidence-based recommendations for evaluation, referral, and management are provided to help guide clinicians in the care of 3q29 deletion patients.

Craniofacial features of 3q29 deletion syndrome: Application of next-generation phenotyping technology.

3q29 deletion syndrome (3q29del) is a recurrent deletion syndrome associated with neuropsychiatric disorders and congenital anomalies. Dysmorphic facial features have been described but not systematically characterized. This study aims to detail the 3q29del craniofacial phenotype and use a machine learning approach to categorize individuals with 3q29del through analysis of 2D photos. Detailed dysmorphology exam and 2D facial photos were ascertained from 31 individuals with 3q29del. Photos were used to train the next-generation phenotyping algorithm DeepGestalt (Face2Gene by FDNA, Inc, Boston, MA) to distinguish 3q29del cases from controls and all other recognized syndromes. Area under the curve of receiver operating characteristic curves (AUC-ROC) was used to determine the capacity of Face2Gene to identify 3q29del cases against controls. In this cohort, the most common observed craniofacial features were prominent forehead (48.4%), prominent nose tip (35.5%), and thin upper lip vermillion (25.8%). The FDNA technology showed an ability to distinguish cases from controls with an AUC-ROC value of 0.873 (p = 0.006) and led to the inclusion of 3q29del as one of the supported syndromes. This study found a recognizable facial pattern in 3q29del, as observed by trained clinical geneticists and next-generation phenotyping technology. These results expand the potential application of automated technology such as FDNA in identifying rare genetic syndromes, even when facial dysmorphology is subtle.

MR1-Independent Activation of Human Mucosal-Associated Invariant T Cells by Mycobacteria.

Tuberculosis (TB) is the leading cause of mortality from a single infectious agent, Mycobacterium tuberculosis Relevant immune targets of the partially efficacious TB vaccine bacille Calmette-Guérin (BCG) remain poorly defined. Mucosal-associated invariant T (MAIT) cells are MHC-related protein 1 (MR1)-restricted T cells, which are reactive against M. tuberculosis, and underexplored as potential TB vaccine targets. We sought to determine whether BCG vaccination activated mycobacteria-specific MAIT cell responses in humans. We analyzed whole blood samples from M. tuberculosis-infected South African adults who were revaccinated with BCG after a six-month course of isoniazid preventative therapy. In vitro BCG stimulation potently induced IFN-γ expression by phenotypic (CD8+CD26+CD161+) MAIT cells, which constituted the majority (75%) of BCG-reactive IFN-γ-producing CD8+ T cells. BCG revaccination transiently expanded peripheral blood frequencies of BCG-reactive IFN-γ+ MAIT cells, which returned to baseline frequencies a year following vaccination. In another cohort of healthy adults who received BCG at birth, 53% of mycobacteria-reactive-activated CD8 T cells expressed CDR3α TCRs, previously reported as MAIT TCRs, expressing the canonical TRAV1-2-TRAJ33 MAIT TCRα rearrangement. CD26 and CD161 coexpression correlated with TRAV1-2+CD161+ phenotype more accurately in CD8+ than CD4-CD8- MAIT cells. Interestingly, BCG-induced IFN-γ expression by MAIT cells in vitro was mediated by the innate cytokines IL-12 and IL-18 more than MR1-induced TCR signaling, suggesting TCR-independent activation. Collectively, the data suggest that activation of blood MAIT cells by innate inflammatory cytokines is a major mechanism of responsiveness to vaccination with whole cell vaccines against TB or in vitro stimulation with mycobacteria (Clinical trial registration: NCT01119521).

New phenotypes associated with 3q29 duplication syndrome: Results from the 3q29 registry.

3q29 duplication syndrome (3q29dup) is a rare genomic disorder caused by a 1.6 Mb duplication (GRCh38 chr3:195,998,000-197,623,000). Case reports indicate the 3q29dup is likely to be pathogenic, but the full range of manifestations is not well understood. We used the 3q29 registry (https://3q29.com) to ascertain 31 individuals with 3q29dup, the largest cohort ever surveyed in a systematic way. For comparison, we ascertained 117 individuals with the reciprocal 3q29 deletion and 64 typically developing controls. We used a custom medical and demographic questionnaire to assess physical and developmental phenotypes, and two standardized instruments, the Social Responsiveness Scale and Child Behavior Checklist/Adult Behavior Checklist, to assess social disability. Participants with 3q29dup report a high rate of problems in the first year of life (80.6%), including feeding problems (55%), failure to gain weight (42%), hypotonia (39%), and respiratory distress (29%). In early childhood, learning problems (71.0%) and seizures (25.8%) are common. Additionally, the rate of self-reported autism spectrum disorder diagnoses (39%) is substantially elevated compared to the general population, suggesting that the 3q29 duplication may be an autism susceptibility locus. This is the most comprehensive description of 3q29dup to date. Our findings can be used to develop evidence-based strategies for early intervention and management of 3q29dup.

Comprehensive phenotyping of neuropsychiatric traits in a multiplex 3q29 deletion family: a case report.

BACKGROUND: 3q29 deletion syndrome is associated with a range of medical, neurodevelopmental, and psychiatric phenotypes. The deletion is usually de novo but cases have been reported where the deletion is inherited from apparently unaffected parents. The presence of these unaffected or mildly affected individuals suggests there may be an ascertainment bias for severely affected cases of 3q29 deletion syndrome, thus the more deleterious consequence of the 3q29 deletion may be overestimated. However, a substantial fraction of 3q29 deletion syndrome morbidity is due to psychiatric illness. In many case reports, probands and transmitting parents are not systematically evaluated for psychiatric traits. Here we report results from a systematic phenotyping protocol for neurodevelopmental and neuropsychiatric traits applied to all 3q29 deletion carriers in a multiplex family. CASE PRESENTATION: Through the 3q29 registry at Emory University, a multiplex family was identified where three offspring had a paternally inherited 3q29 deletion. We evaluated all 4 3q29 deletion family members using our previously described standardized, systematic phenotyping protocol. The transmitting parent reported no psychiatric history, however upon evaluation he was discovered to meet criteria for multiple psychiatric diagnoses including previously undiagnosed schizoaffective disorder. All four 3q29 deletion individuals in the pedigree had multiple psychiatric diagnoses that interfered with quality of life and prohibited successful academic and occupational functioning. Cognitive ability for all individuals was average or below average, but within the normal range. CONCLUSIONS: This is the first case report of inherited 3q29 deletion syndrome where all affected individuals in the pedigree have been comprehensively and systematically evaluated for neurodevelopmental and psychiatric symptoms, using a standard battery of normed instruments administered by expert clinicians. Our investigation reveals that individuals with 3q29 deletion syndrome may have psychiatric morbidity that is debilitating, but only apparent through specialized evaluation by an expert. In the absence of appropriate evaluation, individuals with 3q29 deletion syndrome may suffer from psychiatric illness but lack avenues for access to care. The individuals evaluated here all have cognition in the normal range alongside multiple psychiatric diagnoses each, suggesting that cognitive ability alone is not a representative proxy for 3q29 deletion-associated disability. These results require replication in a larger cohort of individuals with 3q29 deletion syndrome.

Communities Healing And Transforming Trauma (CHATT): A Trauma-Informed Speakers' Bureau for Survivors of Violence.

There is increasing recognition of the value of consumer participation in advocacy and community activism. Among trauma survivors, finding a sense of purpose and a way to make meaning from the trauma experience has been termed "survivor mission," and may include a call to social action, involvement in social justice activities, or public speaking. The current study describes the development of a trauma-informed trauma-survivor speakers' bureau (CHATT) and presents quantitative and qualitative outcome findings. The CHATT program encompasses (1) a speaker training component, (2) public speaking activities, and (3) speaking support groups. Trauma survivors (N = 27) who received trauma mental health (MH) services and were in the later stages of recovery completed the two-part seven-hour speaker training and subsequently presented talks at 13 venues to 192 audience members during a three-year study period. Speakers completed baseline measures prior to the training, and follow-up measures at six months and one year to assess posttraumatic growth (PTG) and self-efficacy. Audience members completed an assessment of change in beliefs about key speaker advocacy goals, as well as emotional reactions and satisfaction with talks. Results revealed PTG and speaking self-efficacy increased for speakers after one-year post-training. Audience ratings of talks averaged in the high range except for one domain. Ratings differed by audience type and number of speakers, and increased as the program matured. Key speaker advocacy successes including state policy changes, limitations, and implications for future research and development are discussed.

Bacillus Calmette-Guérin (BCG) Revaccination of Adults with Latent Mycobacterium tuberculosis Infection Induces Long-Lived BCG-Reactive NK Cell Responses.

One third of the global population is estimated to be latently infected with Mycobacterium tuberculosis We performed a phase I randomized controlled trial of isoniazid preventive therapy (IPT) before revaccination with bacillus Calmette-Guérin (BCG) in healthy, tuberculin skin test-positive (≥15-mm induration), HIV-negative South African adults. We hypothesized that preclearance of latent bacilli with IPT modulates BCG immunogenicity following revaccination. Frequencies and coexpression of IFN-γ, TNF-α, IL-2, IL-17, and/or IL-22 in CD4 T cells and IFN-γ-expressing CD8 T, γδ T, CD3(+)CD56(+) NKT-like, and NK cells in response to BCG were measured using whole blood intracellular cytokine staining and flow cytometry. We analyzed 72 participants who were revaccinated with BCG after IPT (n = 33) or without prior IPT (n = 39). IPT had little effect on frequencies or cytokine coexpression patterns of M. tuberculosis- or BCG-specific responses. Revaccination transiently boosted BCG-specific Th1 cytokine-expressing CD4, CD8, and γδ T cells. Despite high frequencies of IFN-γ-expressing BCG-reactive CD3(+)CD56(+) NKT-like cells and CD3(-)CD56(dim) and CD3(-)CD56(hi) NK cells at baseline, BCG revaccination boosted these responses, which remained elevated up to 1 y after revaccination. Such BCG-reactive memory NK cells were induced by BCG vaccination in infants, whereas in vitro IFN-γ expression by NK cells upon BCG stimulation was dependent on IL-12 and IL-18. Our data suggest that isoniazid preclearance of M. tuberculosis bacilli has little effect on the magnitude, persistence, or functional attributes of lymphocyte responses boosted by BCG revaccination. Our study highlights the surprising durability of BCG-boosted memory NKT-like and NK cells expressing antimycobacterial effector molecules, which may be novel targets for tuberculosis vaccines.

Study protocol for The Emory 3q29 Project: evaluation of neurodevelopmental, psychiatric, and medical symptoms in 3q29 deletion syndrome.

BACKGROUND: 3q29 deletion syndrome is caused by a recurrent hemizygous 1.6 Mb deletion on the long arm of chromosome 3. The syndrome is rare (1 in 30,000 individuals) and is associated with mild to moderate intellectual disability, increased risk for autism and anxiety, and a 40-fold increased risk for schizophrenia, along with a host of physical manifestations. However, the disorder is poorly characterized, the range of manifestations is not well described, and the underlying molecular mechanism is not understood. We designed the Emory 3q29 Project to document the range of neurodevelopmental and psychiatric manifestations associated with 3q29 deletion syndrome. We will also create a biobank of samples from our 3q29 deletion carriers for mechanistic studies, which will be a publicly-available resource for qualified investigators. The ultimate goals of our study are three-fold: first, to improve management and treatment of 3q29 deletion syndrome. Second, to uncover the molecular mechanism of the disorder. Third, to enable cross-disorder comparison with other rare genetic syndromes associated with neuropsychiatric phenotypes. METHODS: We will ascertain study subjects, age 6 and older, from our existing registry ( 3q29deletion.org ). Participants and their families will travel to Atlanta, GA for phenotypic assessments, with particular emphasis on evaluation of anxiety, cognitive ability, autism symptomatology, and risk for psychosis via prodromal symptoms and syndromes. Evaluations will be performed using standardized instruments. Structural, diffusion, and resting-state functional MRI data will be collected from eligible study participants. We will also collect blood from the 3q29 deletion carrier and participating family members, to be banked at the NIMH Repository and Genomics Resource (NRGR). DISCUSSION: The study of 3q29 deletion has the potential to transform our understanding of complex disease. Study of individuals with the deletion may provide insights into long term care and management of the disorder. Our project describes the protocol for a prospective study of the behavioral and clinical phenotype associated with 3q29 deletion syndrome. The paradigm described here could easily be adapted to study additional CNV or single gene disorders with high risk for neuropsychiatric phenotypes, and/or transferred to other study sites, providing a means for data harmonization and cross-disorder analysis.

"Playing Hooky" Health Messages: Apprehension, Impression Management, and Deception.

This study investigates playing hooky in higher education classrooms and associates this behavior with students' communicative dispositions, instructor perceptions, and language use. We define "playing hooky" as students skipping class and explaining their absence to their instructor with deceptive health messages. The purpose of Study 1, an online survey (N = 177), is to further understand the characteristics of students who engage in this type of deceptive health communication. Study 1 measures communication apprehension and perceived instructor credibility in students who had played hooky from class and those who had not. Findings reveal that students who communicate playing hooky health messages (a) reported more instructor communication apprehension and (b) perceived the instructors with whom they had played hooky to be less credible. Study 2 uses facework theory and MEH analysis to reveal the different linguistic strategies students use to communicate (a) truthful health messages (N = 165) and (b) deceptive heath messages (N = 82) to their instructor following an absence. Results demonstrate that students' facework strategies are more geared toward saving instructors' negative face in the deceptive health message condition. Implications of both studies are offered.

Corneal hysteresis in patients with glaucoma-like optic discs, ocular hypertension and glaucoma.

BACKGROUND: To compare corneal hysteresis (CH) measurements between patients with glaucoma, ocular hypertension (OHT) and glaucoma-like optic discs (GLD)- defined as a cup to disc ratio greater than or equal to 0.6 with normal intraocular pressure (IOP) and visual fields. The secondary aim was to investigate whether corneal resistance factor (CRF) and central corneal thickness (CCT) differ between patient groups. METHODS: In this cross sectional study a total of 123 patients (one eye each) were recruited from a glaucoma outpatient department to undergo ocular response analyser (ORA) testing and ultrasound pachymetry as well as clinical examination. A One-way Analysis of Covariance (ANCOVA) was conducted to evaluate the mean difference in CH between the three diagnostic groups (glaucoma, OHT and GLD) correcting for potential confounding factors, IOP and age. Analysis was repeated for CRF and CCT. RESULTS: There was a significant difference in mean CH across the three diagnosis groups; F(2, 115) = 96.95; p < 0.001. Mean CH significantly higher for GLD compared to glaucoma (mean difference 1.83, p < 0.001), and significantly higher for OHT compared to glaucoma (mean difference 2.35, p < 0.001). Mean CH was slightly lower in patients with GLD than those with OHT but this difference was not statistically significant. A similar pattern was seen when the analysis was repeated for CRF and CCT. CONCLUSIONS: Higher CH in GLD and OHT compared to glaucoma suggests increased viscoelasticity of ocular tissues may have a protective role against glaucoma.

Integrating Emotions Into the Critical Interpretive Synthesis.

Critical interpretive synthesis is a particular form of systematic review that critically examines the decisions made by authors while conducting and publishing about their research and practices. It differs from empirical syntheses of qualitative research by emphasizing the interpreted and constructed nature of this form of secondary analysis. In this article, we extend previous literature on critical interpretive syntheses by highlighting the integration of emotional responses when developing critical questions for interrogating the literature and interpreting results. Our extension of the critical interpretive synthesis is illustrated through examples from five studies examining literature in our own field of music therapy, as well as related fields of disability studies, mental health, music psychology, and child welfare. The methodology we have refined uses an iterative and recursive method that promotes increased critical awareness of the assumptions driving the production of research in health contexts.

Exploring the literature on music participation and social connectedness for young people with intellectual disability: A critical interpretive synthesis.

BACKGROUND: This article explores the literature on social connectedness and music for young people with disability. It then critically examines the level of congruence between the reported literature to date and current rights-based disability studies discourse. METHOD: A critical interpretive synthesis was used to examine 27 articles referencing the use of music for social connectedness. Areas of focus in the review are the nature of connections being fostered in music programs, the use of voice and collaboration. RESULTS: The majority of music programs reported on closed groups. Outdated 'expert' models of working persist. The use of participants' voice in the literature is growing, although there is a lack of collaboration and negative reporting. CONCLUSION: A shift in thinking heralds greater collaboration with participants, although this could be broadened to include decisions on research agendas, planning and evaluation. There is also need for active fostering of broader socio-musical pathways.

Folic Acid Supplementation of Female Mice, with or without Vitamin B-12, before and during Pregnancy and Lactation Programs Adiposity and Vascular Health in Adult Male Offspring.

BACKGROUND: The developmental origins of health and disease theory suggest that disturbances in the fetal and early postnatal environment contribute to chronic adulthood diseases, such as type 2 diabetes and cardiovascular disease. Greater adiposity and insulin resistance have been reported in children of women with high erythrocyte folate but poor vitamin B-12 status during pregnancy. The mechanisms underlying this relation are not known. OBJECTIVE: The objective of this study was to investigate the effects of maternal supplemental folic acid, with or without vitamin B-12, on adiposity, glucose homeostasis, and vascular health in adult male offspring mice. METHODS: Female C57BL/6J mice were fed a control diet (M-CON, 2 mg folic acid/kg, 50 µg vitamin B-12/kg) or a folic acid-supplemented diet with [10 mg folic acid/kg, 50 µg vitamin B-12/kg (SFA+B12)] or without [10 mg folic acid/kg, no vitamin B-12 (SFA-B12)] vitamin B-12 for 6 wk before mating and during pregnancy and lactation. The offspring were weaned onto a control diet (16% energy from fat) or a western diet (45% energy from fat) until 23 wk of age. The effects of maternal diet on adiposity, vascular function, and glucose tolerance were assessed in 6 groups of adult male offspring: control diet-fed M-CON, SFA+B12, and SFA-B12 and western diet-fed M-CON, SFA+B12, and SFA-B12. RESULTS: Control and western diet-fed SFA-B12 and SFA+B12 offspring had smaller visceral and subcutaneous adipose tissue than M-CON offspring (P < 0.05). Control SFA-B12 and SFA+B12 offspring had lower serum total adiponectin and vitamin B-12 concentrations and lower NADPH oxidase 2 expression in aorta compared with M-CON offspring (P < 0.05). These effects were not observed in western diet-fed offspring. CONCLUSIONS: Folic acid supplementation of female mice before and during pregnancy and lactation, with or without dietary vitamin B-12, affects adult male offspring adiposity, vascular function, and one-carbon metabolism in those fed a control diet but not a western diet.

Feasibility of a web-based dementia feeding skills training program for nursing home staff.

Nursing home (NH) staff do not receive adequate training for providing feeding assistance to residents with dementia who exhibit aversive feeding behaviors (e.g., clamping mouth shut). The result is often low meal intake for these residents. This feasibility study tested a web-based dementia feeding skills program for staff in two United States NHs. Randomly assigned, the intervention staff received web-based dementia feeding skills training with coaching. Both groups participated in web-based pre-/post-tests assessing staff knowledge and self-efficacy; and meal observations measured NH staff and resident feeding behaviors, time for meal assistance, and meal intake. Aversive feeding behaviors increased in both groups of residents; however, the intervention NH staff increased the amount of time spent providing assistance and meal intake doubled. In the control group, less time was spent providing assistance and meal intake decreased. This study suggests that training staff to use current clinical practice guidelines improves meal intake.

Behavioral Phenotypes and Comorbidity in 3q29 Deletion Syndrome: Results from the 3q29 Registry.

3q29 deletion syndrome (3q29del) is associated with a significantly increased risk for neurodevelopmental and neuropsychiatric disorders. However, the full spectrum of behavioral phenotypes associated with 3q29del is still evolving. Individuals with 3q29del (n = 96, 60.42% male) or their guardian completed the Achenbach Child or Adult Behavior Checklist (CBCL/ABCL) via the online 3q29 registry (3q29deletion.org). Typically developing controls (n = 57, 49.12% male) were ascertained as a comparison group. We analyzed mean performance on the CBCL/ABCL for individuals with 3q29del and controls across composite, DSM-keyed, and developmental scales; and the relationship between CBCL/ABCL performance and clinical and developmental phenotypes for individuals with 3q29del. Individuals with 3q29del showed significantly elevated behavioral and developmental impairment relative to controls across CBCL/ABCL domains. A substantial proportion of study participants with 3q29del scored in the Borderline or Clinical range for composite and DSM-keyed scales, indicating significant behavioral problems that may require clinical evaluation. We found that the preschool CBCL DSM-keyed autism spectrum problems scale is a potential screening tool for autism spectrum disorder (ASD) for individuals with 3q29del; CBCL/ABCL DSM-keyed scales were not accurate screeners for anxiety disorders or attention-deficit/hyperactivity disorder (ADHD) in our study sample. We identified a high degree of psychiatric comorbidity in individuals with 3q29del, with 60.42% (n = 58) of individuals with 3q29del scoring in the Borderline or Clinical range on two or more DSM-keyed CBCL/ABCL scales. Finally, we found that the degree of developmental delay in participants with 3q29del does not explain the increased behavioral problems observed on the CBCL/ABCL. The CBCL/ABCL can be used as screening tools in populations such as 3q29del, even in the presence of substantial psychiatric comorbidity. These results expand our understanding of the phenotypic spectrum of 3q29del and demonstrate an effective method for recruiting and phenotyping a large sample of individuals with a rare genetic disorder.