Food Choice and Dietary Perspectives of Young, Urban, Black Pregnant Women: A Focus Group Study.

Black pregnant women in Chicago are disproportionately affected by maternal morbidity and mortality and are more likely to reside in neighborhoods that experience greater economic hardships and food apartheid than any other race/ethnicity. Addressing social determinants of health such as structural inequities, economic environment, and food apartheid issues may provide insights into eliminating Black maternal morbidity and mortality disparities. This study explores food choice determinants and dietary perspectives of young, urban, Black pregnant women. Two audio-recorded focus groups were conducted in Chicago, IL between March 2019 and June 2019 to discuss pregnancy experiences and factors affecting maternal nutrition. Thematic analysis was used to identify the codes, themes, and subthemes of the data. Data analysis was guided by the Social Ecological Model (SEM) as a theoretical framework. Eleven, young, Black women were recruited. Three major themes were discussed across the SEM levels that influenced food choice including food access, stress and family influences on eating, and the need for nutritional education during pregnancy. These choices were primarily rooted in the detrimental effects of food apartheid experienced within the participants' neighborhoods. Therefore, acknowledging, understanding, and addressing food apartheid and its impact on Black maternal health disparities is needed in clinical practice, research, and policy change.

Mediterranean Diet Adherence and Depressive Symptoms among a Nationally Representative Sample of Pregnant Women in the United States.

BACKGROUND: Prenatal depression affects ∼12% of pregnant women in the United States and is associated with an increased risk of adverse birth outcomes and maternal mortality. Adherence to a healthy dietary pattern may reduce and/or protect against depressive symptoms. OBJECTIVES: To investigate the relationship between adherence to a Mediterranean diet and depressive symptoms among pregnant women in the United States. METHODS: We used data from the National Health and Nutrition Examination Survey (2005-2018, N = 540) and included pregnant women aged 18-44 y with a positive urine pregnancy test. The Mediterranean diet score (aMED) was calculated from 1 24-h recall; aMED typically ranges from 0-9, but in these analyses, it ranged from 0-8 because alcohol was not included. The aMED score was dichotomized as high (>3) compared with low (≤3). The Patient Health Questionnaire-9 (PHQ-9), which measures depressive symptoms, was dichotomized as lower compared with higher (PHQ-9 score ≥10), based on the clinical cutoff for patient referral. Our primary model employed logistic regression to investigate the association between aMED adherence and high depressive symptoms when controlling for socio-demographics (age, racial/ethnicity, education, poverty, and relationship status), total calories, and prepregnancy body mass index (kg/m2). We also modeled the PHQ-9 score as a continuous variable using a random-effects model. RESULTS: About 5% of pregnant women had moderate to severe depressive symptoms, and 45% were highly adherent to a Mediterranean diet. Higher adherence to a Mediterranean diet was associated with lower odds of depressive symptoms (odds ratio: 0.31, 95% confidence interval: 0.10, 0.98). Results were not significant for the continuous PHQ-9 score (ß: -0.30; 95% confidence interval: -0.90, 0.30). CONCLUSIONS: Adherence to a Mediterranean diet may have the potential to lower depressive symptoms among pregnant women; however, these results should be interpreted with caution. Nevertheless, considering the public health significance of promoting mental wellness among pregnant women, this relationship merits further examination using experimental designs.

Correction: OjiNjideka Hemphill et al. Feasibility Study of Lactobacillus Plantarum 299v Probiotic Supplementation in an Urban Academic Facility among Diverse Pregnant Individuals. Nutrients 2023, 15, 875.

There was an error in the original publication [...].

Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial.

OBJECTIVE: This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age. METHODS: A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months. Secondary outcomes were prevalence of drug-resistant epilepsy, additional developmental outcomes, and safety of vigabatrin. RESULTS: Of 84 infants enrolled, 12 were screen failures, 4 went straight to open label vigabatrin, and 12 were not randomized (normal EEG throughout). Fifty-six were randomized to early vigabatrin (n = 29) or placebo (n = 27). Nineteen of 27 in the placebo arm transitioned to open label vigabatrin, with a median delay of 44 days after randomization. Bayley-III cognitive composite scores at 24 months were similar for participants randomized to vigabatrin or placebo. Additionally, no significant differences were found between groups in overall epilepsy incidence and drug-resistant epilepsy at 24 months, time to first seizure after randomization, and secondary developmental outcomes. Incidence of infantile spasms was lower and time to spasms after randomization was later in the vigabatrin group. Adverse events were similar across groups. INTERPRETATION: Preventative treatment with vigabatrin based on EEG epileptiform activity prior to seizure onset does not improve neurocognitive outcome at 24 months in TSC children, nor does it delay onset or lower the incidence of focal seizures and drug-resistant epilepsy at 24 months. Preventative vigabatrin was associated with later time to onset and lower incidence of infantile spasms. ANN NEUROL 2023.

Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Primary mitochondrial myopathies (PMMs) encompass a group of genetic disorders that impair mitochondrial oxidative phosphorylation, adversely affecting physical function, exercise capacity, and quality of life (QoL). Current PMM standards of care address symptoms, with limited clinical impact, constituting a significant therapeutic unmet need. We present data from MMPOWER-3, a pivotal, phase-3, randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of elamipretide in participants with genetically confirmed PMM. METHODS: After screening, eligible participants were randomized 1:1 to receive either 24 weeks of elamipretide at a dose of 40 mg/d or placebo subcutaneously. Primary efficacy endpoints included change from baseline to week 24 on the distance walked on the 6-minute walk test (6MWT) and total fatigue on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA). Secondary endpoints included most bothersome symptom score on the PMMSA, NeuroQoL Fatigue Short-Form scores, and the patient global impression and clinician global impression of PMM symptoms. RESULTS: Participants (N = 218) were randomized (n = 109 elamipretide; n = 109 placebo). The m0ean age was 45.6 years (64% women; 94% White). Most of the participants (n = 162 [74%]) had mitochondrial DNA (mtDNA) alteration, with the remainder having nuclear DNA (nDNA) defects. At screening, the most frequent bothersome PMM symptom on the PMMSA was tiredness during activities (28.9%). At baseline, the mean distance walked on the 6MWT was 336.7 ± 81.2 meters, the mean score for total fatigue on the PMMSA was 10.6 ± 2.5, and the mean T score for the Neuro-QoL Fatigue Short-Form was 54.7 ± 7.5. The study did not meet its primary endpoints assessing changes in the 6MWT and PMMSA total fatigue score (TFS). Between the participants receiving elamipretide and those receiving placebo, the difference in the least squares mean (SE) from baseline to week 24 on distance walked on the 6MWT was -3.2 (95% CI -18.7 to 12.3; p = 0.69) meters, and on the PMMSA, the total fatigue score was -0.07 (95% CI -0.10 to 0.26; p = 0.37). Elamipretide treatment was well-tolerated with most adverse events being mild to moderate in severity. DISCUSSION: Subcutaneous elamipretide treatment did not improve outcomes in the 6MWT and PMMSA TFS in patients with PMM. However, this phase-3 study demonstrated that subcutaneous elamipretide is well-tolerated. TRIAL REGISTRATION INFORMATION: Trial registered with clinicaltrials.gov, Clinical Trials Identifier: NCT03323749; submitted on October 12, 2017; first patient enrolled October 9, 2017. CLINICALTRIALS: gov/ct2/show/NCT03323749?term = elamipretide&draw = 2&rank = 9. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that elamipretide does not improve the 6MWT or fatigue at 24 weeks compared with placebo in patients with primary mitochondrial myopathy.

Structural Violence and Stress Experiences of Young Pregnant Black People.

INTRODUCTION: Approximately 10-20% of individuals suffer from mental health concerns during the prenatal period due to their vulnerability and emotional responses to stressful events. Mental health disorders are more likely to be disabling and persistent for people of color, and they are less likely to seek treatment due to stigma. Young pregnant Black people report experiencing stress due to isolation, feelings of conflict, lack of material and emotional resources, and support from significant others. Although many studies have reported the types of stressors experienced, personal resources, emotional stress responses on pregnancy, and mental health outcomes, there is limited data on young Black women's perceptions of these factors. METHODS: This study utilizes the Health Disparities Research Framework to conceptualize drivers of stress related to maternal health outcomes for young Black women. We conducted a thematic analysis to identify stressors for young Black women. RESULTS: Findings revealed the following overarching themes: Societal stress of being young, Black, and pregnant; Community level systems that perpetuate stress and structural violence; Interpersonal level stressors; Individual level effects of stress on mom and baby; and Coping with stress. DISCUSSION: Acknowledging and naming structural violence and addressing structures that create and fuel stress for young pregnant Black people are important first steps to interrogating systems that allow for nuanced power dynamics and for recognizing the full humanity of young pregnant Black people.

Establishing a pediatric acute stroke protocol: experience of a new pediatric stroke program and predictors of acute stroke.

Introduction: Pediatric stroke is among the top 10 causes of death in pediatrics. Rapid recognition and treatment can improve outcomes in select patients, as evidenced by recent retrospective studies in pediatric thrombectomy. We established a collaborative protocol involving the vascular neurology and pediatric neurology division in our institution to rapidly diagnose and treat pediatric suspected stroke. We also prospectively collected data to attempt to identify predictors of acute stroke in pediatric patients. Methods: IRB approval was obtained to prospectively collect clinical data on pediatric code stroke activations based on timing metrics in resident-physician note templates. The protocol emphasized magnetic resonance imaging over computed tomography imaging when possible. We analyzed performance of the system with descriptive statistics. We then performed a Bayesian statistical analysis to search for predictors of pediatric stroke. Results: There were 40 pediatric code strokes over the 2.5-year study period with a median age of 10.8 years old. 12 (30%) of patients had stroke, and 28 (70%) of code stroke patients were diagnosed with a stroke mimic. Median time from code stroke activation to completion of imaging confirming or ruling out stroke was 1 h. In the Bayesian analysis, altered mental status, hemiparesis, and vasculopathy history were associated with increased odds of stroke, though credible intervals were wide due to the small sample size. Conclusion: A trainee developed and initiated pediatric acute stroke protocol quickly implemented a hospital wide change in management that led to rapid diagnosis and triage of pediatric stroke and suspected stroke. No additional personnel or resources were needed for this change, and we encourage other hospitals and emergency departments to implement similar systems. Additionally, hemiparesis and altered mental status were predictors of stroke for pediatric acute stroke activation in our Bayesian statistical analysis. However credible intervals were wide due to the small sample size. Further multicenter data collection could more definitively analyze predictors of stroke, as well as the help in the creation of diagnostic tools for clinicians in the emergency setting.

Development of cancer surveillance guidelines in ataxia telangiectasia: A Delphi-based consensus survey of international experts.

BACKGROUND/OBJECTIVES: Ataxia telangiectasia (A-T) is a multiorgan disorder with increased vulnerability to cancer. Despite this increased cancer risk, there are no widely accepted guidelines for cancer surveillance in people affected by A-T. We aimed to understand the current international practice regarding cancer surveillance in A-T and agreed-upon approaches to develop cancer surveillance in A-T. DESIGN/METHODS: We used a consensus development method, the e-Delphi technique, comprising three rounds. Round 1 consisted of a Delphi questionnaire and a survey that collected the details of respondents' professional background, experience, and current practice of cancer surveillance in A-T. Rounds 2 and 3 were designed based on previous rounds and modified according to the comments made by the panellists. The pre-specified consensus threshold was ≥75% agreement. RESULTS: Thirty-five expert panellists from 13 countries completed the study. The survey indicated that the current practice of cancer surveillance varies widely between experts and centres'. Consensus was reached that evidence-based guidelines are needed for cancer surveillance in people with A-T, with separate recommendations for adults and children. Statements relating to the tests that should be included, the age for starting and stopping cancer surveillance and the optimal surveillance interval were also agreed upon, although in some areas, the consensus was that further research is needed. CONCLUSION: The international expert consensus statement confirms the need for evidence-based cancer surveillance guidelines in A-T, highlights key features that the guidelines should include, and identifies areas of uncertainty in the expert community. This elucidates current knowledge gaps and will inform the design of future clinical trials.

Corrigendum to "A new pathogenic POLG variant" [Molecular Genetics and Metabolism Reports 32 (2022) 100890].

[This corrects the article DOI: 10.1016/j.ymgmr.2022.100890.].

Associations between plant-based diets, plant foods and botanical supplements with gestational diabetes mellitus: a systematic review protocol.

INTRODUCTION: Gestational diabetes mellitus (GDM) is one of the most common health complications during pregnancy. Medical nutrition therapy is the mainstay of treatment for GDM, however, there is no current consensus on optimal dietary approaches to prevent or control hyperglycaemia in pregnancy. The aim of this systematic review is to assess the relationships between plant-based dietary patterns, plant foods and botanical dietary supplements with GDM and maternal glycaemic biomarkers. METHODS AND ANALYSIS: A predefined search strategy was used on 16 June 2021, to search PubMed, Embase and CINAHL Plus with Full Text (EBSCOhost), as well as ClinicalTrials.gov, for studies published as original articles in English. Articles will be included if they are human observational studies or clinical trials and will be excluded if they are review articles or conference abstracts. We will use Cochrane's risk of bias tools for interventions that are parallel arm (Risk of Bias tool for randomised trials version 2 (RoB 2)) and single arm, non-randomised intervention studies (Risk of Bias In Non-randomised Studies-of Interventions (ROBINS-I)). For observational, case-control and cross-sectional studies, we will use the National Heart, Lung and Blood Institute's quality assessment tools. Data will be synthesised in a narrative format describing significant results as well as presenting the results of the quality assessment of studies. ETHICS AND DISSEMINATION: This systematic review does not require ethical approval as primary data will not be collected. The review will be published in a peer-reviewed journal and disseminated electronically and in print. PROSPERO REGISTRATION NUMBER: CRD42022306915.

Feasibility Study of Lactobacillus Plantarum 299v Probiotic Supplementation in an Urban Academic Facility among Diverse Pregnant Individuals.

(1) Background: Despite iron intake recommendations, over a quarter of pregnant individuals have iron deficiency. Lactobacillus plantarum 299v (Lp299v®) enhances iron absorption in non-pregnant populations and may have positive effects in pregnancy among those with sufficient iron stores; however, no studies have evaluated the effect of Lp299v® on maternal and neonatal iron status among individuals at risk for iron deficiency anemia in pregnancy. Thus, this study aims to assess the feasibility and preliminary efficacy of daily oral Lp299v® maternal supplementation among diverse pregnant individuals. (2) Methods: In this double-blind placebo-controlled randomized supplementation feasibility study, participants were randomized to probiotic Lp299v® + prenatal vitamin with iron or placebo + prenatal vitamin with iron from 15-20 weeks of gestation through delivery. (3) Results: Of the 20 enrolled and randomized participants, 58% (7/12) from the Lp299v® group and 75% (6/8) from the placebo group were retained. Adherence to supplementation was 72% for Lp299v®/placebo and 73% for the prenatal vitamin. A slower decline in maternal hematological and iron parameters across pregnancy was observed in the Lp299v® group compared to placebo. (4) Conclusions: Lp299v® may be a tolerable therapy during pregnancy and has the potential to affect maternal and neonatal hematological and iron status.

Use of Elamipretide in patients assigned treatment in the compassionate use program: Case series in pediatric patients with rare orphan diseases.

Several mitochondrial diseases are caused by pathogenic variants that impair membrane phospholipid remodeling, with no FDA-approved therapies. Elamipretide targets the inner mitochondrial membrane where it binds to cardiolipin, resulting in improved membrane stability, cellular respiration, and ATP production. In clinical trials, elamipretide produced clinical and functional improvements in adults and adolescents with mitochondrial disorders, such as primary mitochondrial myopathy and Barth syndrome; however, experience in younger patients is limited and to our knowledge, these are the first case reports on the safety and efficacy of elamipretide treatment in children under 12 years of age. We describe the use of elamipretide in patients with mitochondrial disorders to provide dosing parameters in patients aged <12 years.

Obstetric experiences of young black mothers: An intersectional perspective.

BACKGROUND: In Chicago, maternal morbidity and mortality is six times more likely among Black birthing people than white, despite policy initiatives to promote maternal health equity. Disparities in maternal morbidity and mortality reflect experiences of structural inequities - including limited quality obstetric care, implicit bias, and racism resulting patient mistrust in the health care system, inadequate social support, and financial insecurity. Although there is published literature on Black women's experiences with obstetric care, including experiences with individual and structural racism, little is known about the intersection of age and race and experiences with health care. The purpose of this study was to explore the maternal health and pregnancy experiences of young Black women utilizing an intersectional theoretical lens. METHODS: In this study, we conducted two focus groups in a sample of 11 young Black pregnant people. We conducted a thematic analysis to identify codes, themes, and subthemes of the data. RESULTS: We developed two overarching themes: obstetric racism and obstetric resistance. To elucidate how obstetric racism framed our participants' healthcare experiences, we identified sub-themes: intersectional identities as young Black women, medical mistrust, and pregnancy trauma. The second major theme describes ways in which participants protected themselves against obstetric racism to engender positive health experiences. These methods of resistance included identifying advocates and relying on trusted providers. CONCLUSIONS: The current standard of obstetric care in the US is suboptimal due to individual and structural racism. This study provides unique data on the experiences with health care for young, Black pregnant individuals and delivers valuable insight into how individual and structural racism impacts obstetric care for young Black women.

Efficacy of behavioral interventions to improve maternal mental health and breastfeeding outcomes: a systematic review.

BACKGROUND: Despite extensive benefits and high intentions, few mothers breastfeed exclusively for the recommended duration. Maternal mental health is an important underlying factor associated with barriers and reduced rates of breastfeeding intent, initiation, and continuation. Given evidence of a bidirectional association between maternal mental health and breastfeeding, it is important to consider both factors when examining the efficacy of interventions to improve these outcomes. The purpose of this manuscript is to review the literature on the efficacy of behavioral interventions focused on both maternal mental health and breastfeeding outcomes, examining the intersection of the two. METHODS: This systematic review was completed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Studies were selected if they were available in English, used primary experimental design, and used a behavioral intervention type to examine maternal mental health and breastfeeding outcomes. Articles were identified from PubMed, CINAHL, Embase, and PsycINFO from database inception to 3 March 2022. Study quality was assessed using the Cochrane Risk of Bias tool. Results were synthesized by intervention success for 1. Mental health and breastfeeding, 2. Breastfeeding only, 3. Mental health only, and 4. No intervention effect. PROSPERO CRD42021224228. RESULTS: Thirty interventions reported in 33 articles were identified, representing 15 countries. Twelve studies reported statistically significant positive effect of the intervention on both maternal mental health and breastfeeding; most showing a decrease in self-report depressive and/or anxiety symptoms in parallel to an increase in breastfeeding duration and/or exclusivity. Common characteristics of successful interventions were a) occurring across pregnancy and postpartum, b) delivered by hospital staff or multidisciplinary teams, c) offered individually, and d) designed to focus on breastfeeding and maternal mental health or on breastfeeding only. Our results are not representative of all countries, persons, experiences, circumstances, or physiological characteristics. CONCLUSIONS: Interventions that extend the perinatal period and offer individualized support from both professionals and peers who collaborate through a continuum of settings (e.g., health system, home, and community) are most successful in improving both mental health and breastfeeding outcomes. The benefits of improving these outcomes warrant continued development and implementation of such interventions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021224228.

Recruitment and Retention of Urban Pregnant Women to a Clinical Study Administering an Oral Isotope Dietary Tracer.

Introduction: Pregnant women are a vulnerable population that are difficult to engage in clinical research. We report successful recruitment and retention strategies used in a longitudinal pilot study of urban racially/ethnically diverse pregnant women that involved administration of an orally ingested isotope tracer, multiple venipunctures, biopsy of placenta after delivery, and cord or placental blood collection. Materials and Methods: We used direct strategies to recruit English-speaking obese and nonobese pregnant women aged 17-45 years, who were in the third trimester of pregnancy. The study required data collection at 32-34 and 34-36 gestational weeks and delivery. Strategies included frequent personal engagement with participants and staff to build relationships and trust, tangible appreciation, and the study team being present at delivery. In addition, leveraging hospital information technology (IT) services was critical to ensure retention through labor and delivery (LD). Results: A racially (52% Black, 23% White, and 10% other) and ethnically (15% Hispanic or Latinx) diverse sample of pregnant women was enrolled. Of the 52 women enrolled, 85% of women completed all procedures. Conclusions: This is the first report of successful strategies for recruitment and retention of racially/ethnically diverse pregnant women in a longitudinal study requiring oral administration of an isotope tracer. Personal engagement with multiple touch points, starting with recruitment and continuing regularly throughout the third trimester, was the most successful strategy. Creating and maintaining relationships with the LD providers and staff and utilizing hospital IT, including targeted electronic medical record alerts, ensured successful retention for the duration of the study. Trial Registration: Not applicable.

A new pathogenic POLG variant.

POLG gene mutations are the most common causes of inherited mitochondrial disorders. The enzyme produced by this gene is responsible for the replication and repair of mitochondrial DNA. To date, around 300 pathogenic variants have been described in this gene. The resulting clinical outcomes of POLG mutations are widely variable in both phenotype and severity. There is considerable overlap in the phenotype of the so-called POLG syndromes with no clear genotype-phenotype correlation. Here we describe a newly discovered pathogenic variant in the POLG gene in a 7-year-old male that died of uncontrollable refractory status epilepticus. Genetic epilepsy panel sequencing identified two variants in the POLG gene, the common p.A467T pathological mutation and a novel p.S809R POLG variant found in trans with the p.A467T POLG that accompanied a severely reduced mitochondrial DNA level in the patient's tissues.

Phenotypic and genetic spectrum of ATP6V1A encephalopathy: a disorder of lysosomal homeostasis.

Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal genes encode for a redundant set of subunits allowing the composition of diverse V-ATPase complexes with specific properties and expression. Sixteen subunits have been linked to human disease. Here we describe 26 patients harbouring 20 distinct pathogenic de novo missense ATP6V1A variants, mainly clustering within the ATP synthase α/ß family-nucleotide-binding domain. At a mean age of 7 years (extremes: 6 weeks, youngest deceased patient to 22 years, oldest patient) clinical pictures included early lethal encephalopathies with rapidly progressive massive brain atrophy, severe developmental epileptic encephalopathies and static intellectual disability with epilepsy. The first clinical manifestation was early hypotonia, in 70%; 81% developed epilepsy, manifested as developmental epileptic encephalopathies in 58% of the cohort and with infantile spasms in 62%; 63% of developmental epileptic encephalopathies failed to achieve any developmental, communicative or motor skills. Less severe outcomes were observed in 23% of patients who, at a mean age of 10 years and 6 months, exhibited moderate intellectual disability, with independent walking and variable epilepsy. None of the patients developed communicative language. Microcephaly (38%) and amelogenesis imperfecta/enamel dysplasia (42%) were additional clinical features. Brain MRI demonstrated hypomyelination and generalized atrophy in 68%. Atrophy was progressive in all eight individuals undergoing repeated MRIs. Fibroblasts of two patients with developmental epileptic encephalopathies showed decreased LAMP1 expression, Lysotracker staining and increased organelle pH, consistent with lysosomal impairment and loss of V-ATPase function. Fibroblasts of two patients with milder disease, exhibited a different phenotype with increased Lysotracker staining, decreased organelle pH and no significant modification in LAMP1 expression. Quantification of substrates for lysosomal enzymes in cellular extracts from four patients revealed discrete accumulation. Transmission electron microscopy of fibroblasts of four patients with variable severity and of induced pluripotent stem cell-derived neurons from two patients with developmental epileptic encephalopathies showed electron-dense inclusions, lipid droplets, osmiophilic material and lamellated membrane structures resembling phospholipids. Quantitative assessment in induced pluripotent stem cell-derived neurons identified significantly smaller lysosomes. ATP6V1A-related encephalopathy represents a new paradigm among lysosomal disorders. It results from a dysfunctional endo-lysosomal membrane protein causing altered pH homeostasis. Its pathophysiology implies intracellular accumulation of substrates whose composition remains unclear, and a combination of developmental brain abnormalities and neurodegenerative changes established during prenatal and early postanal development, whose severity is variably determined by specific pathogenic variants.

Feasibility of a Web-Based Intervention to Prevent Perinatal Depression and Promote Human Milk Feeding: Randomized Pilot Trial.

BACKGROUND: Mothers who identify as Black or African American are more likely to report depressed moods in late pregnancy and early postpartum and have the lowest rates of human milk feeding compared with all other racial groups in the United States. Internet interventions offer the potential to extend preventative and supportive services as they address key barriers, particularly for those navigating the complex and vulnerable early postpartum period. However, there is limited evidence on the feasibility of such interventions for preventing perinatal mental health disorders and improving human milk feeding outcomes in Black mothers. OBJECTIVE: This pilot study aimed to assess the feasibility and preliminary findings of a web-based cognitive behavioral therapy-based internet intervention, with and without human milk feeding education and support, to prevent perinatal depression and promote human milk feeding in Black mothers. METHODS: Participants were Black-identifying individuals between 20 and 28 weeks of pregnancy with human milk feeding intention and mild to moderate depressive symptoms (Patient Health Questionnaire scores 5-14). Participants were randomized to either Sunnyside, a 6-week cognitive behavioral therapy-based web-based intervention, or Sunnyside Plus, which included additional education and support to promote human milk feeding. Assessments occurred at baseline, third trimester (end of antenatal treatment), 6 weeks postpartum (end of postpartum treatment), and 12 weeks postpartum. The primary focus of this randomized pilot trial was the feasibility and preliminary outcomes of mental health and human milk feeding. RESULTS: A total of 22 tertiary-educated participants were randomized. The mean number of log-ins was 7.3 (SD 5.3) for Sunnyside and 13.8 (SD 10.5) for Sunnyside Plus. Scores of depression and anxiety measures remained below the clinical threshold for referral to treatment in both groups. All the participants initiated human milk feeding (18/18, 100%). Most participants reported at least some human milk feeding at both 6 and 12 weeks postpartum (6/7, 86%; 11/11, 100%, or 10/10, 100%, for Sunnyside and Sunnyside Plus, respectively). CONCLUSIONS: The results suggest that tertiary-educated Black mothers at risk for perinatal depression and who intended to human milk feed were receptive to and satisfied with a web-based cognitive behavioral therapy-based internet intervention, with and without human milk feeding education and support. Preliminary findings indicate that both Sunnyside and Sunnyside Plus interventions have the potential to affect symptoms of depression, anxiety, and human milk feeding outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04128202; https://www.clinicaltrials.gov/ct2/show/NCT04128202.

A randomized, double-blind trial of triheptanoin for drug-resistant epilepsy in glucose transporter 1 deficiency syndrome.

OBJECTIVE: This study was undertaken to evaluate efficacy and long-term safety of triheptanoin in patients >1 year old, not on a ketogenic diet, with drug-resistant seizures associated with glucose transporter 1 deficiency syndrome (Glut1DS). METHODS: UX007G-CL201 was a randomized, double-blind, placebo-controlled trial. Following a 6-week baseline period, eligible patients were randomized 3:1 to triheptanoin or placebo. Dosing was titrated to 35% of total daily calories over 2 weeks. After an 8-week placebo-controlled period, all patients received open-label triheptanoin through Week 52. RESULTS: The study included 36 patients (15 children, 13 adolescents, eight adults). A median 12.6% reduction in overall seizure frequency was observed in the triheptanoin arm relative to baseline, and a 13.5% difference was observed relative to placebo (p = .58). In patients with absence seizures only (n = 9), a median 62.2% reduction in seizure frequency was observed in the triheptanoin arm relative to baseline. Only one patient with absence seizures only was present in the control group, preventing comparison. No statistically significant differences in seizure frequency were observed. Common treatment-emergent adverse events included diarrhea, vomiting, abdominal pain, and nausea, mostly mild or moderate in severity. No serious adverse events were considered to be treatment related. One patient discontinued due to status epilepticus. SIGNIFICANCE: Triheptanoin did not significantly reduce seizure frequency in patients with Glut1DS not on the ketogenic diet. Treatment was associated with mild to moderate gastrointestinal treatment-related events; most resolved following dose reduction or interruption and/or medication for treatment. Triheptanoin was not associated with any long-term safety concerns when administered at dose levels up to 35% of total daily caloric intake for up to 1 year.