Maternal prebiotic supplementation during pregnancy and lactation modifies the microbiome and short chain fatty acid profile of both mother and infant.

BACKGROUND & AIMS: Improving maternal gut health in pregnancy and lactation is a potential strategy to improve immune and metabolic health in offspring and curtail the rising rates of inflammatory diseases linked to alterations in gut microbiota. Here, we investigate the effects of a maternal prebiotic supplement (galacto-oligosaccharides and fructo-oligosaccharides), ingested daily from <21 weeks' gestation to six months' post-partum, in a double-blinded, randomised placebo-controlled trial. METHODS: Stool samples were collected at multiple timepoints from 74 mother-infant pairs as part of a larger, double-blinded, randomised controlled allergy intervention trial. The participants were randomised to one of two groups; with one group receiving 14.2 g per day of prebiotic powder (galacto-oligosaccharides GOS and fructo-oligosaccharides FOS in ratio 9:1), and the other receiving a placebo powder consisting of 8.7 g per day of maltodextrin. The faecal microbiota of both mother and infants were assessed based on the analysis of bacterial 16S rRNA gene (V4 region) sequences, and short chain fatty acid (SCFA) concentrations in stool. RESULTS: Significant differences in the maternal microbiota profiles between baseline and either 28-weeks' or 36-weeks' gestation were found in the prebiotic supplemented women. Infant microbial beta-diversity also significantly differed between prebiotic and placebo groups at 12-months of age. Supplementation was associated with increased abundance of commensal Bifidobacteria in the maternal microbiota, and a reduction in the abundance of Negativicutes in both maternal and infant microbiota. There were also changes in SCFA concentrations with maternal prebiotics supplementation, including significant differences in acetic acid concentration between intervention and control groups from 20 to 28-weeks' gestation. CONCLUSION: Maternal prebiotic supplementation of 14.2 g per day GOS/FOS was found to favourably modify both the maternal and the developing infant gut microbiome. These results build on our understanding of the importance of maternal diet during pregnancy, and indicate that it is possible to intervene and modify the development of the infant microbiome by dietary modulation of the maternal gut microbiome.

Nutritional Criminology: Why the Emerging Research on Ultra-Processed Food Matters to Health and Justice.

There is mounting concern over the potential harms associated with ultra-processed foods, including poor mental health and antisocial behavior. Cutting-edge research provides an enhanced understanding of biophysiological mechanisms, including microbiome pathways, and invites a historical reexamination of earlier work that investigated the relationship between nutrition and criminal behavior. Here, in this perspective article, we explore how this emergent research casts new light and greater significance on previous key observations. Despite expanding interest in the field dubbed 'nutritional psychiatry', there has been relatively little attention paid to its relevancy within criminology and the criminal justice system. Since public health practitioners, allied mental health professionals, and policymakers play key roles throughout criminal justice systems, a holistic perspective on both historical and emergent research is critical. While there are many questions to be resolved, the available evidence suggests that nutrition might be an underappreciated factor in prevention and treatment along the criminal justice spectrum. The intersection of nutrition and biopsychosocial health requires transdisciplinary discussions of power structures, industry influence, and marketing issues associated with widespread food and social inequalities. Some of these discussions are already occurring under the banner of 'food crime'. Given the vast societal implications, it is our contention that the subject of nutrition in the multidisciplinary field of criminology-referred to here as nutritional criminology-deserves increased scrutiny. Through combining historical findings and cutting-edge research, we aim to increase awareness of this topic among the broad readership of the journal, with the hopes of generating new hypotheses and collaborations.

Feasibility and Usability of EnergyPoints: A Mobile Health App to Guide Acupressure Use for Cancer Symptom Management.

OBJECTIVE: To examine the feasibility and usability of EnergyPoints™, an innovative mobile health app that teaches and guides people with cancer to implement daily acupressure to self-manage their fatigue and sleep disturbances. METHODS AND INTERVENTION: The study used an integrated agile, human-centered approach. Adults (age 18 years and over) with cancer experiencing at least moderate fatigue, and living in the Greater New York City community, were recruited from social media, patient advocacy groups, and referrals. Twenty participants (in 3 sprints of 3, 5, and 12) were video-recorded thinking aloud while using the app for the first time. They then used the app at home to self-administer acupressure (twice daily for 1 week) while continuously wearing a fitness tracker. Each participant completed an exit interview and modified Computer System Usability Questionnaire post-participation. RESULTS: Participants were ages 40 to 76 years and 65% female; 65% were non-Hispanic white. Mean pass rates per ritual exceeded 80%. Users completed (totally or partially) greater than 90% of stimulating acupressure and 70% of relaxing acupressure rituals. Sprint 3 SPs totally completed at least 1 ritual 87% of the time. The majority agreed or strongly agreed the app was easy to use (90%), easy to learn (85%), easy to understand (75%), and effective in helping perform self-acupressure (85%). In an analysis of ease of completing 5 key tasks, all successfully completed the tasks; 3 users required some assistance. Of 654 usability statements, those coded as personal experience/context (197), content related to acupressure learning (105), and content related to the onboarding/profile (71) were most frequent. The design team integrated recommendations into the app before the next sprint. CONCLUSIONS: Findings supported feasibility and usability, as well as acceptability, and led to significant alterations and improvements. EnergyPoints™ offers an opportunity to mainstream acupressure and help cancer survivors self-manage their symptoms.

Perinatal Women's Perspectives of, and Engagement in, Digital Emotional Well-Being Training: Mixed Methods Study.

BACKGROUND: Psychological distress in the early postpartum period can have long-lasting deleterious effects on a mother's well-being and negatively affect her infant's development. Intervention approaches based in contemplative practices such as mindfulness and loving-kindness and compassion are intended to alleviate distress and cultivate well-being and can be delivered effectively as digital mental health interventions (DMHIs). OBJECTIVE: To understand the feasibility of engaging perinatal women in digital interventions, this study aimed to document participants' experiences in the Mums Minds Matter (MMM) study, a pilot randomized controlled trial comparing mindfulness, loving-kindness and compassion, and progressive muscle relaxation training delivered in a digital format and undertaken during pregnancy. To assess the different stages of engagement during and after the intervention, we adapted the connect, attend, participate, enact (CAPE) framework that is based on the idea that individuals go through different stages of engagement before they are able to enact change. METHODS: The MMM study was nested within a longitudinal birth cohort, The ORIGINS Project. We aimed to recruit 25 participants per randomization arm. Data were collected sequentially during the intervention through regular web-based surveys over 8 weeks, with opportunities to provide regular feedback. In the postintervention phase, qualitative data were collected through purposive sampling. RESULTS: Of 310 eligible women, 84 (27.1% [connect rate]) enrolled to participate in MMM. Of the remaining 226 women who did not proceed to randomization, 223 (98.7%) failed to complete the baseline surveys and timed out of eligibility (after 30 weeks' gestation), and 3 (1.3%) displayed high psychological distress scores. Across all program groups, 17 (20% [attend rate]) of the 84 participants actively opted out, although more may have disengaged from the intervention but did not withdraw. The main reasons for withdrawal were busy life and other priorities. In this study, we assessed active engagement and ongoing skills use (participate and enact) through postintervention interviews. We undertook 15 participant interviews, conducted 1 month to 3 months after the intervention. Our results provide insights into participant barriers and enablers as well as app changes, such as the ability to choose topics, daily reminders, case studies, and diversity in sounds. Implementing a DMHI that is brief, includes frequent prompts or nudges, and is easily accessible is a key strategy to target perinatal women. CONCLUSIONS: Our research will enable future app designs that are sufficiently nuanced to maximize the uptake, engagement, and application of mental health skills and contemplative practices in the perinatal period. Providing convenient access to engaging and effective prevention programs is critical and should be part of prenatal self-care. Our research underscores the appeal and feasibility of digital intervention approaches based in contemplative practices for perinatal women. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) 12620000672954p; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000672954p. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/19803.

Monoacylglycerol Lipase Protects the Presynaptic Cannabinoid 1 Receptor from Desensitization by Endocannabinoids after Persistent Inflammation.

Cannabinoid-targeted pain therapies are increasing with the expansion of cannabis legalization, however, their efficacy may be limited by pain-induced adaptations in the cannabinoid system. Cannabinoid receptor subtype 1 (CB1R) inhibition of spontaneous, GABAergic miniature IPSCs (mIPSCs) and evoked IPSCs (eIPSCs) in the ventrolateral periaqueductal gray (vlPAG) were compared in slices from naive and inflamed male and female Sprague Dawley rats. Complete Freund's Adjuvant (CFA) injections into the hindpaw induced persistent inflammation. In naive rats, exogenous cannabinoid agonists robustly reduce both eIPSCs and mIPSCs. After 5-7 d of inflammation, the effects of exogenous cannabinoids are significantly reduced because of CB1R desensitization via GRK2/3, as function is recovered in the presence of the GRK2/3 inhibitor, Compound 101 (Cmp101). Inhibition of GABA release by presynaptic µ-opioid receptors in the vlPAG does not desensitize with persistent inflammation. Unexpectedly, while CB1R desensitization significantly reduces the inhibition produced by exogenous agonists, depolarization-induced suppression of inhibition protocols that promote 2-arachidonoylglycerol (2-AG) synthesis exhibit prolonged CB1R activation after inflammation. 2-AG tone is detected in slices from CFA-treated rats when GRK2/3 is blocked, suggesting an increase in 2-AG synthesis after persistent inflammation. Inhibiting 2-AG degradation with the monoacylglycerol lipase (MAGL) inhibitor JZL184 during inflammation results in the desensitization of CB1Rs by endocannabinoids that is reversed with Cmp101. Collectively, these data indicate that persistent inflammation primes CB1Rs for desensitization, and MAGL degradation of 2-AG protects CB1Rs from desensitization in inflamed rats. These adaptations with inflammation have important implications for the development of cannabinoid-based pain therapeutics targeting MAGL and CB1Rs.SIGNIFICANCE STATEMENT Presynaptic G-protein-coupled receptors are resistant to desensitization. Here we find that persistent inflammation increases endocannabinoid levels, priming presynaptic cannabinoid 1 receptors for desensitization on subsequent addition of exogenous agonists. Despite the reduced efficacy of exogenous agonists, endocannabinoids have prolonged efficacy after persistent inflammation. Endocannabinoids readily induce cannabinoid 1 receptor desensitization if their degradation is blocked, indicating that endocannabinoid concentrations are maintained at subdesensitizing levels and that degradation is critical for maintaining endocannabinoid regulation of presynaptic GABA release in the ventrolateral periaqueductal gray during inflammatory states. These adaptations with inflammation have important implications for the development of cannabinoid-based pain therapies.

Self-administered acupressure for veterans with chronic back pain: Study design and methodology of a type 1 hybrid effectiveness implementation randomized controlled trial.

BACKGROUND: Chronic low back pain is prevalent and disabling in Veterans, but effective pain management is challenging. Clinical practice guidelines emphasize multimodal pain management including evidence-based complementary and integrative health treatments such as acupressure as a first line of care. Unfortunately, the ability to replicate interventions, cost, resources, and limited access are implementation barriers. Self-administered acupressure has shown positive effects on pain and can be practiced anywhere with little to no side effects. METHODS/DESIGN: The aims of this Type 1 hybrid effectiveness implementation randomized controlled trial are 1) to determine effectiveness of a self-administered acupressure protocol at improving pain interference and secondary outcomes of fatigue, sleep quality, and disability in 300 Veterans with chronic low back pain, and 2) evaluate implementation barriers and facilitators to scale-up acupressure utilization within Veterans Health Administration (VHA). Participants randomized to the intervention will receive instruction on acupressure application using an app that facilitates daily practice for 6 weeks. During weeks 6 through 10, participants will discontinue acupressure to determine sustainability of effects. Participants randomized to waitlist control will continue their usual care for pain management and receive study materials at the end of the study period. Outcomes will be collected at baseline and at 6- and 10-weeks post baseline. The primary outcome is pain interference, measured by the PROMIS pain interference scale. Using established frameworks and a mixed methods approach, we will evaluate intervention implementation. DISCUSSION: If acupressure is effective, we will tailor strategies to support implementation in the VHA based on study findings. TRIAL REGISTRATION NUMBER: NCT05423145.

Interrogating Components of 2 Diet Quality Indices in Pregnancy using a Supervised Statistical Mixtures Approach.

BACKGROUND: The Healthy Eating Index (HEI)-2015 and Alternative Healthy Eating Index (AHEI)-2010 evaluate diet holistically in pregnancy. However, it remains unclear how individual index components interact to contribute to health. OBJECTIVES: To evaluate associations of HEI-2015 and AHEI-2010 components with gestational length using traditional and novel statistical methods in a prospective cohort. METHODS: Pregnant women completed a 3-mo food-frequency questionnaire (FFQ) at median 13 wk gestation to calculate the HEI-2015 or AHEI-2010. Covariate-adjusted linear regression models evaluated associations of HEI-2015 and AHEI-2010 total scores and individual components (one at a time and simultaneously adjusted) with gestational length. Covariate-adjusted weighted quantile sum regression models evaluated 1) associations of HEI-2015 or AHEI-2010 components as mixtures with gestational length and 2) contributions of components to these associations. RESULTS: Each 10-point increase in HEI-2015 and AHEI-2010 total score was associated with 0.11 (95% CI: -0.05, 0.27) and 0.14 (95% CI: 0.00, 0.28) wk longer gestation, respectively. In individual or simultaneously adjusted HEI-2015 models, higher intakes of seafood/plant proteins, total protein foods, greens/beans, and saturated fats but lower intakes of added sugars and refined grains were associated with longer gestational length. For the AHEI-2010, higher intake of nuts/legumes and lower intake of sugar-sweetened beverages (SSBs)/fruit juice were associated with longer gestational length. Jointly, 10% increases in HEI-2015 or AHEI-2010 mixtures were associated with 0.17 (95% CI: 0.001, 0.34) and 0.18 (95% CI: 0.05, 0.30) wk longer gestational length, respectively. Seafood/plant protein, total protein foods, dairy, greens/beans, and added sugars were the largest contributors to the HEI-2015 mixture. Nuts/legumes, SSBs/fruit juice, sodium, and DHA/EPA were the largest contributors to the AHEI-2010 mixture. Associations were less precise but consistent in women with spontaneous labors. CONCLUSIONS: Compared to traditional methods, associations of diet index mixtures with gestational length were more robust and identified unique contributors. Additional studies could consider interrogating these statistical approaches using other dietary indices and health outcomes.

Pediatric Sedation Unit: A Safe, Effective, and Satisfactory Alternative to Outpatient Pediatric Urological Procedures Under Anesthesia.

INTRODUCTION: The operating room is an increasingly expensive and limited resource. The aim of this study was to evaluate the efficacy, safety, cost, and parental satisfaction of transitioning minor pediatric urology procedures from an operating room setting to a pediatric sedation unit. METHODS: Minor urological procedures were transitioned from the operating room to the pediatric sedation unit if they could be completed in 20 minutes using minimal instrumentation. Information regarding patient demographics, procedure characteristics, rates of success and complications, and cost were collected from urology procedures performed in the pediatric sedation unit between August 2019 and September 2021. Patient demographics and cost data from the most common urology procedures performed in the pediatric sedation unit were compared to data from historical controls of cases occurring in the operating room. Parent surveys were performed following the completion of procedures in the pediatric sedation unit. RESULTS: A total of 103 patients, ranging from 6-207 months old (mean 72 months), underwent procedures in the pediatric sedation unit. The most common procedures were lysis of adhesions and meatotomy. All procedures were successfully completed with procedural sedation, and no procedure was complicated by serious sedation adverse events. The cost reduction for lysis of adhesions in the pediatric sedation unit was 53.5% compared to the operating room, and meatotomy was 27.9%, leading to approximately $57,000 cost savings per year. Fifty families completed a follow-up satisfaction survey, and 83% of parents were satisfied with the care their family received. CONCLUSIONS: The pediatric sedation unit can provide a successful and cost-efficient alternative to the operating room while preserving safety and high rates of parental satisfaction.

The association between genetically elevated polyunsaturated fatty acids and risk of cancer.

BACKGROUND: The causal relevance of polyunsaturated fatty acids (PUFAs) for risk of site-specific cancers remains uncertain. METHODS: Using a Mendelian randomization (MR) framework, we assessed the causal relevance of PUFAs for risk of cancer in European and East Asian ancestry individuals. We defined the primary exposure as PUFA desaturase activity, proxied by rs174546 at the FADS locus. Secondary exposures were defined as omega 3 and omega 6 PUFAs that could be proxied by genetic polymorphisms outside the FADS region. Our study used summary genetic data on 10 PUFAs and 67 cancers, corresponding to 562,871 cases and 1,619,465 controls, collected by the Fatty Acids in Cancer Mendelian Randomization Collaboration. We estimated odds ratios (ORs) for cancer per standard deviation increase in genetically proxied PUFA exposures. FINDINGS: Genetically elevated PUFA desaturase activity was associated (P < 0.0007) with higher risk (OR [95% confidence interval]) of colorectal cancer (1.09 [1.07-1.11]), esophageal squamous cell carcinoma (1.16 [1.06-1.26]), lung cancer (1.06 [1.03-1.08]) and basal cell carcinoma (1.05 [1.02-1.07]). There was little evidence for associations with reproductive cancers (OR = 1.00 [95% CI: 0.99-1.01]; Pheterogeneity = 0.25), urinary system cancers (1.03 [0.99-1.06], Pheterogeneity = 0.51), nervous system cancers (0.99 [0.95-1.03], Pheterogeneity = 0.92) or blood cancers (1.01 [0.98-1.04], Pheterogeneity = 0.09). Findings for colorectal cancer and esophageal squamous cell carcinoma remained compatible with causality in sensitivity analyses for violations of assumptions. Secondary MR analyses highlighted higher omega 6 PUFAs (arachidonic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid) as potential mediators. PUFA biosynthesis is known to interact with aspirin, which increases risk of bleeding and inflammatory bowel disease. In a phenome-wide MR study of non-neoplastic diseases, we found that genetic lowering of PUFA desaturase activity, mimicking a hypothetical intervention to reduce cancer risk, was associated (P < 0.0006) with increased risk of inflammatory bowel disease but not bleeding. INTERPRETATION: The PUFA biosynthesis pathway may be an intervention target for prevention of colorectal cancer and esophageal squamous cell carcinoma but with potential for increased risk of inflammatory bowel disease. FUNDING: Cancer Resesrch UK (C52724/A20138, C18281/A19169). UK Medical Research Council (MR/P014054/1). National Institute for Health Research (NIHR202411). UK Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4). National Cancer Institute (R00 CA215360). National Institutes of Health (U01 CA164973, R01 CA60987, R01 CA72520, U01 CA74806, R01 CA55874, U01 CA164973 and U01 CA164973).

Effects of Yoga and Aerobic Exercise on Verbal Fluency in Physically Inactive Older Adults: Randomized Controlled Trial (FitForAge).

Purpose: To compare the effects on verbal fluency of a supported yoga-based exercise intervention to an aerobic exercise intervention and a wait-list control group. Participants and Methods: Eighty-two physically-inactive but otherwise healthy adults (mean age 72.5 years, range 65-85, 77% female) were recruited into a 12-week, three-group, parallel randomized controlled trial. Participants were supported to complete ≥3 Hatha yoga classes per/week or ≥3 structured aerobic exercise sessions/week. A wait-list control group continued usual daily activities only. Verbal fluency, including total-FAS, animals, and verbs, was assessed before and after interventions. Group effects were assessed using analysis of covariance (ANCOVA). Results: Twenty-seven participants were randomized to yoga, 29 to aerobic exercise and 26 to a waitlist. At 12-week follow-up, compared to baseline, there were increases in mean total-FAS in the yoga (+5.0 words, p=0.002) and aerobic exercise groups (+6.6 words, p=0.004). Mean total-FAS in the wait-list control group remained stable (-0.5 words, p=0.838). There were medium-magnitude estimated treatment effects on total-FAS for yoga versus wait-list control and aerobic exercise versus wait-list control: Hedges' g=0.51 (p=0.213) and 0.57 (p=0.098) respectively. In addition, small-to-medium magnitude estimated treatment effects were seen on animals and verbs for yoga versus wait-list control and aerobic exercise versus wait-list control: g=0.28 (p=0.155), 0.19 (p=0.766) and 0.50 (p=0.085), 0.59 (p=0.233) respectively. Conclusion: Participation in yoga or aerobic exercise was associated with estimated improvements in verbal fluency compared to a non-active control group. Yoga and aerobic exercise may be promising approaches by which to promote cognitive function among older adults. Trial Registration: DRKS00015093, U1111-1217-4248.

Persistent inflammation selectively activates opioid-sensitive phasic-firing neurons within the vlPAG.

The ventrolateral periaqueductal gray (vlPAG) is a key brain area within the descending pain modulatory pathway and an important target for opioid-induced analgesia. The vlPAG contains heterogeneous neurons with respect to neurotransmitter content, receptor and channel expression, and in vivo response to noxious stimuli. This study characterizes intrinsic membrane properties of vlPAG neurons to identify neuron types that respond to inflammation and determine whether the pain-responsive neurons are inhibited by opioids. Surveying 382 neurons identified four neuron types with distinct intrinsic firing patterns: Phasic (48%), Tonic (33%), Onset (10%), and Random (9%). Mu-opioid receptor (MOR) expression was determined by the ability of a selective MOR agonist (DAMGO) to activate G protein-coupled inwardly rectifying potassium channel (GIRK) currents. Opioid-sensitive neurons were observed within each neuron type. Opioid sensitivity did not correlate with other intrinsic firing features, including low-threshold spiking that has been previously proposed to identify opioid-sensitive GABAergic neurons in the vlPAG of mice. Complete Freund's adjuvant (CFA)-induced acute inflammation (2 h) had no effect on vlPAG neuron firing patterns. However, persistent inflammation (5-7 days) selectively activated Phasic neurons through a significant reduction in their firing threshold. Opioid-sensitive neurons were strongly activated compared with the opioid-insensitive Phasic neurons. Overall, this study provides a framework to further identify neurons activated by persistent inflammation so that they may be targeted for future pain therapies.NEW & NOTEWORTHY Intrinsic firing properties define four distinct vlPAG neuron populations, and a subset of each population expresses MORs coupled to GIRK channels. Persistent, but not acute, inflammation selectively activates opioid-sensitive Phasic vlPAG neurons. Although the vlPAG is known to contribute to the descending inhibition of pain, the activation of a single physiologically defined neuron type in the presence of persistent inflammation represents a mechanism by which the vlPAG participates in descending facilitation of pain.

Modulation of in Vitro SARS-CoV-2 Infection by Stephania tetrandra and Its Alkaloid Constituents.

Botanical natural products have been widely consumed for their purported usefulness against COVID-19. Here, six botanical species from multiple sources and 173 isolated natural product compounds were screened for blockade of wild-type (WT) SARS-CoV-2 infection in human 293T epithelial cells overexpressing ACE-2 and TMPRSS2 protease (293TAT). Antiviral activity was demonstrated by an extract from Stephania tetrandra. Extract fractionation, liquid chromatography-mass spectrometry (LC-MS), antiviral assays, and computational analyses revealed that the alkaloid fraction and purified alkaloids tetrandrine, fangchinoline, and cepharanthine inhibited WT SARS-CoV-2 infection. The alkaloids and alkaloid fraction also inhibited the delta variant of concern but not WT SARS-CoV-2 in VeroAT cells. Membrane permeability assays demonstrate that the alkaloids are biologically available, although fangchinoline showed lower permeability than tetrandrine. At high concentrations, the extract, alkaloid fractions, and pure alkaloids induced phospholipidosis in 293TAT cells and less so in VeroAT cells. Gene expression profiling during virus infection suggested that alkaloid fraction and tetrandrine displayed similar effects on cellular gene expression and pathways, while fangchinoline showed distinct effects on cells. Our study demonstrates a multifaceted approach to systematically investigate the diverse activities conferred by complex botanical mixtures, their cell-context specificity, and their pleiotropic effects on biological systems.

Prenatal Care Experiences of Childbearing People With Disabilities in Ontario, Canada.

OBJECTIVE: To explore the care experiences of childbearing people with physical, sensory, and/or intellectual/developmental disabilities during pregnancy. DESIGN: Descriptive qualitative. SETTING: Ontario, Canada, where physician and midwifery care during pregnancy are provided at no direct cost to residents. PARTICIPANTS: Thirty-one people with physical, sensory, and/or intellectual/developmental disabilities (who self-identified as cisgender women [n = 29] and trans or nonbinary persons [n = 2]) who gave birth in the last 5 years. METHODS: We recruited childbearing people with disabilities through disability and parenting organizations, social media, and our team's networks. Using a semistructured guide, we conducted in-person and virtual (e.g., telephone or Zoom) interviews with childbearing people with disabilities in 2019 to 2020. We asked participants about the services they accessed during pregnancy and if services met their needs. We used a reflexive thematic analysis approach to analyze interview data. RESULTS: Across disability groups, we identified four common themes: Unmet Accommodation Needs, Lack of Coordinated Care, Ableism, and Advocacy as a Critical Resource. We found that these experiences manifested in unique ways based on disability type. CONCLUSION: Our findings suggest the need for accessible, coordinated, and respectful prenatal care for people with disabilities, with the requirements of such care depending on the needs of the individual person with a disability. Nurses can play a key role in identifying the needs and supporting people with disabilities during pregnancy. Education and training for nurses, midwives, obstetricians, and other prenatal care providers should focus on disability-related knowledge and respectful prenatal care.

Hyperkalemia in pediatric chronic kidney disease.

BACKGROUND: While hyperkalemia is well described in adult chronic kidney disease (CKD), large studies evaluating potassium trends and risk factors for hyperkalemia in pediatric CKD are lacking. This study aimed to characterize hyperkalemia prevalence and risk factors in pediatric CKD. METHODS: Cross-sectional analysis of Chronic Kidney Disease in Children (CKiD) study data evaluated median potassium levels and percentage of visits with hyperkalemia (K ≥5.5 mmoL/L) in relation to demographics, CKD stage, etiology, proteinuria, and acid-base status. Multiple logistic regression was used to identify risk factors for hyperkalemia. RESULTS: One thousand and fifty CKiD participants with 5183 visits were included (mean age 13.1 years, 62.7% male, 32.9% self-identifying as African American or Hispanic). A percentage of 76.6% had non-glomerular disease, 18.7% had CKD stage 4/5, 25.8% had low CO2, and 54.2% were receiving ACEi/ARB therapy. Unadjusted analysis identified a median serum potassium level of 4.5 mmol/L (IQR 4.1-5.0, p <0.001) and hyperkalemia in 6.6% of participants with CKD stage 4/5. Hyperkalemia was present in 14.3% of visits with CKD stage 4/5 and glomerular disease. Hyperkalemia was associated with low CO2 (OR 7.72, 95%CI 3.05-19.54), CKD stage 4/5 (OR 9.17, 95%CI 4.02-20.89), and use of ACEi/ARB therapy (OR 2.14, 95%CI 1.36-3.37). Those with non-glomerular disease were less frequently hyperkalemic (OR 0.52, 95%CI 0.34-0.80). Age, sex, and race/ethnicity were not associated with hyperkalemia. CONCLUSIONS: Hyperkalemia was observed more frequently in children with advanced stage CKD, glomerular disease, low CO2, and ACEi/ARB use. These data can help clinicians identify high-risk patients who may benefit from earlier initiation of potassium-lowering therapies. A higher resolution version of the Graphical abstract is available as Supplementary information.

Diversifying Amino Acids and Peptides via Deaminative Reductive Cross-Couplings Leveraging High-Throughput Experimentation.

A deaminative reductive coupling of amino acid pyridinium salts with aryl bromides has been developed to enable efficient synthesis of noncanonical amino acids and diversification of peptides. This method transforms natural, commercially available lysine, ornithine, diaminobutanoic acid, and diaminopropanoic acid to aryl alanines and homologated derivatives with varying chain lengths. Attractive features include ability to transverse scales, tolerance of pharma-relevant (hetero)aryls and biorthogonal functional groups, and the applicability beyond monomeric amino acids to short and macrocyclic peptide substrates. The success of this work relied on high-throughput experimentation to identify complementary reaction conditions that proved critical for achieving the coupling of a broad scope of aryl bromides with a range of amino acid and peptide substrates including macrocyclic peptides.

Neighborhood disadvantage is associated with KRAS-mutated non-small cell lung cancer risk.

PURPOSE: It remains unclear why individuals living in disadvantaged neighborhoods have shorter non-small cell lung cancer (NSCLC) survival. It is possible that living in these deprived areas is linked with increased risk of developing aggressive NSCLC biology. Here, we explored the association of somatic KRAS mutations, which are associated with shorter survival in NSCLC patients, and 11 definitions of neighborhood disadvantage spanning socioeconomic and structural environmental elements. METHODS: We analyzed data from 429 NSCLC patients treated at a Comprehensive Cancer Center from 2015 to 2018. Data were abstracted from medical records and each patient's home address was used to assign publicly available indices of neighborhood disadvantage. Prevalence Ratios (PRs) for the presence of somatic KRAS mutations were estimated using modified Poisson regression models adjusted for age, sex, smoking status, race/ethnicity, educational attainment, cancer stage, and histology. RESULTS: In the NSCLC cohort, 29% had KRAS mutation-positive tumors. We found that five deprivation indices of socioeconomic disadvantage were associated with KRAS mutation. A one decile increase in several of these socioeconomic disadvantage indices was associated with a 1.06 to 1.14 increased risk of KRAS mutation. Measures of built structural environment were not associated with KRAS mutation status. CONCLUSION: Socioeconomic disadvantage at the neighborhood level is associated with higher risk of KRAS mutation while disadvantage related to built environmental structural measures was inversely associated. Our results indicate not only that neighborhood disadvantage may contribute to aggressive NSCLC biology, but the pathways linking biology to disadvantage are likely operating through socioeconomic-related stress.

Longitudinal changes in uric acid concentration and their relationship with chronic kidney disease progression in children and adolescents.

BACKGROUND: Elevated serum uric acid concentration is a risk factor for CKD progression. Its change over time and association with CKD etiology and concomitant changes in estimated glomerular filtration rate (eGFR) in children and adolescents are unknown. METHODS: Longitudinal study of 153 children/adolescents with glomerular (G) and 540 with non-glomerular (NG) etiology from the CKD in Children (CKiD) study. Baseline serum uric acid, change in uric acid and eGFR over time, CKD etiology, and comorbidities were monitored. Adjusted linear mixed-effects regression models quantified the relationship between within-person changes in uric acid and concurrent within-person changes in eGFR. RESULTS: Participants with stable uric acid over follow-up had CKD progression which became worse for increased baseline uric acid (average annual percentage changes in eGFR were - 1.4%, - 7.7%, and - 14.7% in those with G CKD with baseline uric acid < 5.5 mg/dL, 5.5 - 7.5 mg/dL, and > 7.5 mg/dL, respectively; these changes were - 1.4%, - 4.1%, and - 8.6% in NG CKD). Each 1 mg/dL increase in uric acid over follow-up was independently associated with significant concomitant eGFR decreases of - 5.7% (95%CI - 8.4 to - 3.0%) (G) and - 5.1% (95%CI - 6.3 to - 4.0%) (NG) for those with baseline uric acid < 5.5 mg/dL and - 4.3% (95%CI - 6.8 to - 1.6%) (G) and - 3.3% (95%CI - 4.1 to - 2.6%) (NG) with baseline uric acid between 5.5 and 7.5 mg/dL. CONCLUSIONS: Higher uric acid levels and increases in uric acid over time are risk factors for more severe progression of CKD in children and adolescents. A higher resolution version of the Graphical abstract is available as Supplementary information.

Increased resting-state thalamocortical functional connectivity in children and young adults with autism spectrum disorder.

There is converging evidence that abnormal thalamocortical interactions contribute to attention deficits and sensory sensitivities in autism spectrum disorder (ASD). However, previous functional MRI studies of thalamocortical connectivity in ASD have produced inconsistent findings in terms of both the direction (hyper vs. hypoconnectivity) and location of group differences. This may reflect, in part, the confounding effects of head motion during scans. In the present study, we investigated resting-state thalamocortical functional connectivity in 8-25 year-olds with ASD and their typically developing (TD) peers. We used pre-scan training, on-line motion correction, and rigorous data quality assurance protocols to minimize motion confounds. ASD participants showed increased thalamic connectivity with temporal cortex relative to TD. Both groups showed similar age-related decreases in thalamic connectivity with occipital cortex, consistent with a process of circuit refinement. Findings of thalamocortical hyperconnectivity in ASD are consistent with other evidence that decreased thalamic inhibition leads to increase and less filtered sensory information reaching the cortex where it disrupts attention and contributes to sensory sensitivity. This literature motivates studies of mechanisms, functional consequences, and treatment of thalamocortical circuit dysfunction in ASD.

Eleven-Year Experience with Selective Adrenal Vein Sampling in Management of Primary Adrenal Hormonal Hypersecretion.

Introduction: Nearly half of the adult population in the United States has been diagnosed with hypertension. Adrenal hormonal hypersecretion is a leading cause of secondary hypertension. Adrenal vein sampling (AVS) may assist in differentiating between unilateral and bilateral adrenal hormonal hypersecretion to identify patients who are candidates for adrenalectomy. We reviewed the use of AVS at our institution along with associated outcomes after adrenalectomy. Materials and Methods: A retrospective chart review was conducted of patients with a diagnosis of primary hyperaldosteronism (PA) or adrenocorticotropic hormone-independent Cushing syndrome (AICS) and who underwent adrenalectomy between January 1, 2010, and December 1, 2021. Patient data of baseline characteristics, preoperative workup, including AVS, and postoperative outcomes were collected and analyzed. Results: Seventy-one patients were identified in the study period (48 PA and 23 AICS). Computed tomography scan identified unilateral adrenal nodules in 52 patients (29 left; and 23 right), bilateral nodules in 13 patients, and no nodules in 6 patients. AVS was performed in 45 patients with PA (93%) and 5 patients with AICS (21%). After surgery, the number of PA patients with hypokalemia or requiring potassium supplementation significantly decreased after adrenalectomy (before surgery: 33 [68.7%]; and after surgery: 5 [10.4%], P < .01). The number of medications required for hypertension in AICS patients also significantly decreased. No major adverse events were noted. Conclusions: Our long-term experience demonstrates the ongoing use of AVS during workup of patients with primary hyperaldosteronism and for select patients with adrenocorticotropic hormone-independent Cushing syndrome. However, a low level of discordance between imaging and AVS findings in PA patients suggests that there may be a subset of patients in whom preoperative AVS is not necessary.

"Food faddists and pseudoscientists!": Reflections on the history of resistance to ultra-processed foods.

The term 'ultra-processed food' emerged in the 1980s, mostly used in reference to highly-processed convenience foods and snacks, often energy-dense, poor in nutrients, and inclusive of various synthetic additives such as emulsifiers, colors, artificial sweeteners, and/or flavor enhancers. Concern over such foods was part of the growing holistic and environmental health movements of the 1970-80s; yet, those who raised alarm about the encroachment of ultra-processed foods were often labeled, especially by industry and their powerful allies, as 'food faddists' and 'pseudoscientists'. Today, the topic of ultra-processed foods is generating massive personal, public, and planetary health interest. However, other than discussing the history of the NOVA food classification system, a useful tool that has allowed researchers to more accurately separate foods based on processing, most lay media and academic articles are ahistorical. That is, there is a tendency to present the term ultra-processed food(s) as a relatively new entrance into the lexicon, and by default, the idea that health-related pushback on ultra-processed foods is a relatively new phenomenon. This omission overlooks decades of determined advocacy and clinical work, much of it by pioneers within the holistic medicine (now integrative, functional, and lifestyle medicine) movement. Here in this reflection paper, the authors will use historical research and reporting to fill in the historical gap and articulate the saliency of why it matters.