Roadmap for the Emerging Field of Cancer Neuroscience.

Mounting evidence indicates that the nervous system plays a central role in cancer pathogenesis. In turn, cancers and cancer therapies can alter nervous system form and function. This Commentary seeks to describe the burgeoning field of "cancer neuroscience" and encourage multidisciplinary collaboration for the study of cancer-nervous system interactions.

Pancreatitis pain quality changes at year 1 follow-up, but GP130 remains a biomarker for pain.

BACKGROUND/OBJECTIVES: Debilitating abdominal pain is a common symptom affecting patients with chronic pancreatitis (CP). CP pain is dynamic due to multiple underlying mechanisms. The objective of this study was to 1) evaluate changes in pain phenotype at one year follow-up and 2) validate putative pain biomarkers in a prospective cohort study. METHODS: The Neuropathic and Nociceptive PROMIS-PQ questionnaires were used to classify pain for participants with in the PROCEED study. Putative serum biomarkers were measured via immunoassay. RESULTS: At enrollment, 17.6 % (120/681) subjects with CP reported no pain in the previous year. Of those, 29 % experienced pain during the 1 yr follow-up whereas 18 % of those with pain prior to enrollment reported no pain during the 1 yr follow-up period. Of the 393 subjects with PROMIS-PQ data at enrollment, 212 also had follow-up data at 1 yr. Approximately half (53.3 %) of those individuals changed pain phenotype between baseline and follow-up. At 1 yr, serum TGFß1 level was negatively correlated with nociceptive T-scores (p = 0.006). GP130 was significantly correlated with both nociceptive (p = 0.012) and neuropathic T-scores (p = 0.043) at 1 yr, which is consistent with the previously published findings. CONCLUSIONS: The positive association between TGFß1 and pain is not maintained over time, suggesting it is a poor pain biomarker. However, serum GP130 is a consistent biomarker for mixed-type pain in CP. Preclinical studies show that targeting TGFß1 or IL-6 (ligand for GP130) is sufficient to inhibit CP pain supporting further investigation of this as a potential therapeutic target.

Impact of hypertensive disorders of pregnancy and gestational diabetes mellitus on offspring cardiovascular health in early adolescence.

BACKGROUND: Adverse pregnancy outcomes, including hypertensive disorders of pregnancy and gestational diabetes mellitus, influence maternal cardiovascular health long after pregnancy, but their relationship to offspring cardiovascular health following in-utero exposure remains uncertain. OBJECTIVE: To examine associations of hypertensive disorders of pregnancy or gestational diabetes mellitus with offspring cardiovascular health in early adolescence. STUDY DESIGN: This analysis used data from the prospective Hyperglycemia and Adverse Pregnancy Outcome Study from 2000 to 2006 and the Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study from 2013 to 2016. This analysis included 3317 mother-child dyads from 10 field centers, comprising 70.8% of Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study participants. Those with pregestational diabetes and chronic hypertension were excluded. The exposures included having any hypertensive disorders of pregnancy or gestational diabetes mellitus vs not having hypertensive disorders of pregnancy or gestational diabetes mellitus, respectively (reference). The outcome was offspring cardiovascular health when aged 10-14 years, on the basis of 4 metrics: body mass index, blood pressure, total cholesterol level, and glucose level. Each metric was categorized as ideal, intermediate, or poor using a framework provided by the American Heart Association. The primary outcome was defined as having at least 1 cardiovascular health metric that was nonideal vs all ideal (reference), and the second outcome was the number of nonideal cardiovascular health metrics (ie, at least 1 intermediate metric, 1 poor metric, or at least 2 poor metrics vs all ideal [reference]). Modified poisson regression with robust error variance was used and adjusted for covariates at pregnancy enrollment, including field center, parity, age, gestational age, alcohol or tobacco use, child's assigned sex at birth, and child's age at follow-up. RESULTS: Among 3317 maternal-child dyads, the median (interquartile) ages were 30.4 (25.6-33.9) years for pregnant individuals and 11.6 (10.9-12.3) years for children. During pregnancy, 10.4% of individuals developed hypertensive disorders of pregnancy, and 14.6% developed gestational diabetes mellitus. At follow-up, 55.5% of offspring had at least 1 nonideal cardiovascular health metric. In adjusted models, having hypertensive disorders of pregnancy (adjusted risk ratio, 1.14 [95% confidence interval, 1.04-1.25]) or having gestational diabetes mellitus (adjusted risk ratio, 1.10 [95% confidence interval, 1.02-1.19]) was associated with a greater risk that offspring developed less-than-ideal cardiovascular health when aged 10-14 years. The above associations strengthened in magnitude as the severity of adverse cardiovascular health metrics increased (ie, with the outcome measured as ≥1 intermediate, 1 poor, and ≥2 poor adverse metrics), albeit the only statistically significant association was with the "1-poor-metric" exposure. CONCLUSION: In this multinational prospective cohort, pregnant individuals who experienced either hypertensive disorders of pregnancy or gestational diabetes mellitus were at significantly increased risk of having offspring with worse cardiovascular health in early adolescence. Reducing adverse pregnancy outcomes and increasing surveillance with targeted interventions after an adverse pregnancy outcome should be studied as potential avenues to enhance long-term cardiovascular health in the offspring exposed in utero.

One children's hospital planning and development process to adhere to the FDA recommendation that babies and young children undergo thyroid function testing after receiving an injection of iodine-containing contrast media for medical imaging.

The United States (US) Food and Drug Administration (FDA) has issued multiple statements and guidelines since 2015 on the topic of thyroid function testing in babies and children through 3 years old after receiving iodinated contrast media for medical imaging exams. In April 2023, the FDA adjusted this recommendation to target babies and young children younger than 4 years of age who have a history of prematurity, very low birth weight, or underlying conditions which affect thyroid gland function, largely in response to solid arguments from expert statements from the American College of Radiology (ACR) which is endorsed by the Society for Pediatric Radiology (SPR), Pediatric Endocrinology Society (PES), and the Society for Cardiovascular Angiography & Intervention (SCAI). Herein we describe our approach and development of a clinical care guideline along with the steps necessary for implementation of the plan including alterations in ordering exams requiring iodinated contrast media, automatic triggering of lab orders, reporting, and follow-up, to address the 2022 FDA guidance statement to monitor thyroid function in children after receiving iodinated contrast media. The newly implemented clinical care guideline at Ann and Robert H. Lurie Children's Hospital of Chicago remains applicable following the 2023 updated recommendation from the FDA. We will track patients less than 3 months of age who undergo thyroid function testing following computed tomography (CT), interventional radiology, and cardiac catheterization exams for which an iodinated contrast media is administered as a clinical care quality initiative.

The phase 1/2 trial of indomethacin in chronic pancreatitis (The PAIR trial): Protocol for a parallel multi-center randomized controlled trial.

BACKGROUND/OBJECTIVES: Current treatments for chronic pancreatitis focus on symptom management and therapeutics targeting disease reversal are lacking. Given the role of the cyclooxygenase-2 (COX-2) enzyme in producing prostaglandin E2 (PGE2), a key component in the inflammatory pathway of chronic pancreatitis, this study evaluates the physiologic effect of oral indomethacin, a COX-2 inhibitor, on PGE2 levels in pancreatic fluid. METHODS: This pilot two-center randomized controlled trial seeks to examine 32 subjects with chronic pancreatitis who have no contraindications to indomethacin. Subjects will be randomized to either oral indomethacin 50 mg twice a day or placebo twice a day for a total of 28 days. Baseline (pre-treatment) assessment of pain and quality of life will be performed using the Brief Pain Inventory and the PROMIS-10 questionnaires, respectively. Biological specimens including blood, urine, and saliva will be collected at pre-treatment and post-treatment(day 28). Endoscopic pancreatic function testing with concomitant pancreatic fluid collection will also be performed pre- and post-treatment to assess the change in pancreatic fluid PGE2 levels. The relationship between pancreatic fluid PGE2 levels with blood and saliva PGE2 levels will be examined. CONCLUSIONS: This study will elucidate the effect of oral indomethacin on PGE2 levels in the pancreas to assess its role in the inflammatory pathway of chronic pancreatitis. Should indomethacin significantly reduce PGE2 levels, this may represent a potential disease-altering treatment for chronic pancreatitis.

Short-Term Complications After Total Thyroidectomy in Children.

INTRODUCTION: Total thyroidectomy for benign disease is becoming more common among children. The purpose of this study was to evaluate 30-day outcomes in children undergoing total thyroidectomy and determine if the short-term outcomes are different in those with a malignant versus benign indication for surgery. METHODS: This retrospective cohort study used the American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-Pediatric) to identify all children who underwent total thyroidectomy from 2015 to 2019. Fisher's exact test was used to compare postoperative outcomes between benign and malignant indications for thyroidectomy. RESULTS: Among 1595 total thyroidectomy patients, 1091 (68.4%) had a benign indication and 504 (31.6%) had a malignant indication. There were 1234 (77.4%) females, and the median age was 14.9 y (interquartile range [IQR] 12.5, 16.6). Average length of stay (LOS) was similar between cohorts (1.7 d for benign and 1.9 d for malignant, P = 0.30). Parathyroid auto-transplantation was performed in 71 (6.5%) patients in the benign cohort and 43 (8.6%) in the malignant cohort (P = 0.15). The most common complications were readmissions (23 [2.1%] benign and 15 [3.0%] malignant, P = 0.29) and reoperations (7 [0.6%] benign and 5 [1.0%] malignant, P = 0.54). Complication profiles were similar between benign and malignant cohorts (2.8% and 4.6%, respectively [P = 0.10]). CONCLUSIONS: Children undergoing total thyroidectomy for benign and malignant indications have low rates of 30-d postoperative complications, suggesting that total thyroidectomy is a safe option for children with benign disease. Evaluation of long-term outcomes is needed.

Neuronally expressed PDL1, not PD1, suppresses acute nociception.

PDL1 is a protein that induces immunosuppression by binding to PD1 expressed on immune cells. In line with historical studies, we found that membrane-bound PD1 expression was largely restricted to immune cells; PD1 was not detectable at either the mRNA or protein level in peripheral neurons using single neuron qPCR, immunolabeling and flow cytometry. However, we observed widespread expression of PDL1 in both sensory and sympathetic neurons that could have important implications for patients receiving immunotherapies targeting this pathway that include unexpected autonomic and sensory related effects. While signaling pathways downstream of PD1 are well established, little to no information is available regarding the intracellular signaling downstream of membrane-bound PDL1 (also known as reverse signaling). Here, we administered soluble PD1 to engage neuronally expressed PDL1 and found that PD1 significantly reduced nocifensive behaviors evoked by algogenic capsaicin. We used calcium imaging to examine the underlying neural mechanism of this reduction and found that exogenous PD1 diminished TRPV1-dependent calcium transients in dissociated sensory neurons. Furthermore, we observed a reduction in membrane expression of TRPV1 following administration of PD1. Exogenous PD1 had no effect on pain-related behaviors in sensory neuron specific PDL1 knockout mice. These data indicate that neuronal PDL1 activation is sufficient to modulate sensitivity to noxious stimuli and as such, may be an important homeostatic mechanism for regulating acute nociception.

Individual adsorption of low volatility pheromones: Amphiphilic molecules on a clean water-air interface.

Environmental conditions can alter olfactory scent and chemical communication among biological species. In particular, odorant molecules interact with aerosols. Thermodynamics variables governing the adsorption from air to water surface of bombykol, the most studied pheromone, and of three derivative molecules, bombykal, bombykoic acid, and bombykyle acetate, are computed by steered and un-biased molecular dynamics in order to compare the role of their polar head group on adsorption on aqueous aerosols. When adsorbed, the molecule center of mass stands at about 1.2 Å from the interface and oscillates on the same length scale, trapped in an energy well. Gibbs energy of adsorption and desorption time of bombykol are found to be 9.2 kBT and 59 µs, respectively. The following ordering between the molecules is observed, reading from the more to the least adsorbed: bombykoic acid > bombykol > bombykoic acetate > bombykal. It originates from a complex interplay of entropy and enthalpy. The entropy and enthalpy of adsorption are discussed in the light of structural arrangement, H-bonding, and hydrophilic tail positioning of the molecules at the interface. Our results show that, when dispersed in the air, pheromones adsorb on aqueous aerosols. However, the individual residence time is quite short on pure water surfaces. Aerosols can, therefore, only have a decisive influence on chemical communication through collective effects or through their chemical composition that is generally more complex than that of a pure water surface.

Clinical correlates of drug-related dreams in opioid use disorder.

BACKGROUND AND OBJECTIVES: Drug-related dreams are commonly reported by individuals in treatment for substance use disorders, which may be distressing. Existing evidence suggests that dream recollection may be influenced by clinically relevant phenomena, such as opioid use and withdrawal, general sleep disturbance, affective symptoms, and chronic pain. However, very few studies have explored drug-related dreams among individuals who screened positive for opioid use disorder (OUD). METHODS: Adults recruited from Amazon Mechanical Turk (MTurk) who screened positive for OUD (N = 154) completed a questionnaire about drug-related dreams, as well as measures assessing sleep, opioid use history, stress, anxiety, and chronic pain. χ2 analyses, one-way analysis of variance, and bivariate correlations, correcting for the false discovery rate, were used as appropriate to explore correlates of (1) recollecting a drug-related dream, and (2) experiencing post-dream craving and distress. RESULTS: Individuals who recollected a past-week drug-related dream were more likely to report other recent sleep disturbances, including poorer sleep quality, greater insomnia symptoms, and a higher risk for sleep apnea. Post-dream craving and distress were both associated with greater insomnia symptoms, poor sleep hygiene behaviors, and greater anxiety symptoms. Individuals who had ever experienced a drug-related dream (recently, or in their lifetime) were more likely to report a history of severe withdrawal, overdose, and intravenous opioid use. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Drug-related dreams were common among individuals in the present sample and were related to other clinically relevant phenomena. Interventions that treat co-occurring OUD, pain, sleep symptoms, and affective symptoms may improve overall well-being in this population.

Defining the Kv2.1-syntaxin molecular interaction identifies a first-in-class small molecule neuroprotectant.

The neuronal cell death-promoting loss of cytoplasmic K+ following injury is mediated by an increase in Kv2.1 potassium channels in the plasma membrane. This phenomenon relies on Kv2.1 binding to syntaxin 1A via 9 amino acids within the channel intrinsically disordered C terminus. Preventing this interaction with a cell and blood-brain barrier-permeant peptide is neuroprotective in an in vivo stroke model. Here a rational approach was applied to define the key molecular interactions between syntaxin and Kv2.1, some of which are shared with mammalian uncoordinated-18 (munc18). Armed with this information, we found a small molecule Kv2.1-syntaxin-binding inhibitor (cpd5) that improves cortical neuron survival by suppressing SNARE-dependent enhancement of Kv2.1-mediated currents following excitotoxic injury. We validated that cpd5 selectively displaces Kv2.1-syntaxin-binding peptides from syntaxin and, at higher concentrations, munc18, but without affecting either synaptic or neuronal intrinsic properties in brain tissue slices at neuroprotective concentrations. Collectively, our findings provide insight into the role of syntaxin in neuronal cell death and validate an important target for neuroprotection.

Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study: newborn anthropometrics and childhood glucose metabolism.

AIMS/HYPOTHESIS: We aimed to examine associations of newborn anthropometric measures with childhood glucose metabolism with the hypothesis that greater newborn birthweight, adiposity and cord C-peptide are associated with higher childhood glucose levels and lower insulin sensitivity. METHODS: Data from the international, multi-ethnic, population-based Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and the HAPO Follow-Up Study were used. The analytic cohort included 4155 children (mean age [SD], 11.4 [1.2] years; 51.0% male). Multiple linear regression was used to examine associations of primary predictors, birthweight, newborn sum of skinfolds (SSF) and cord C-peptide, from HAPO with continuous child glucose outcomes from the HAPO Follow-Up Study. RESULTS: In an initial model that included family history of diabetes and maternal BMI during pregnancy, birthweight and SSF demonstrated a significant, inverse association with 30 min and 1 h plasma glucose levels. In the primary model, which included further adjustment for maternal sum of glucose z scores from an oral glucose tolerance test during pregnancy, the associations were strengthened, and birthweight and SSF were inversely associated with fasting, 30 min, 1 h and 2 h plasma glucose levels. Birthweight and SSF were also associated with higher insulin sensitivity (Matsuda index) (ß = 1.388; 95% CI 0.870, 1.906; p < 0.001; ß = 0.792; 95% CI 0.340, 1.244; p < 0.001, for birthweight and SSF higher by 1 SD, respectively) in the primary model, while SSF, but not birthweight, was positively associated with the disposition index, a measure of beta cell compensation for insulin resistance (ß = 0.034; 95% CI 0.012, 0.056; p = 0.002). Cord C-peptide levels were inversely associated with Matsuda index (ß = -0.746; 95% CI -1.188, -0.304; p < 0.001 for cord C-peptide higher by 1 SD) in the primary model. CONCLUSIONS/INTERPRETATION: This study demonstrates that higher birthweight and SSF are associated with greater childhood insulin sensitivity and lower glucose levels following a glucose load, associations that were further strengthened after adjustment for maternal glucose levels during pregnancy. Graphical abstract.

Single-cell analyses of human pancreas: characteristics of two populations of acinar cells in chronic pancreatitis.

Chronic pancreatitis (CP) is a complex inflammatory disorder with numerous associated genetic and environmental risk factors. The most distressing characteristic of CP is recalcitrant pain, often requiring surgical resection including total pancreatectomy with islet autotransplantation (TPIAT). We studied five consented subjects undergoing pancreatic resection and processed isolated cells for single-cell RNA sequencing (scRNA-Seq). Using high-dimensional transcriptomic cluster analysis, we identified 11 unique cell clusters in the pancreas tissue. These cell clusters include a cluster of undifferentiated/dedifferentiated cells and two unique clusters of acinar cells, one of which appears to be in a transitional stage. To determine the cellular response to protease inhibitor and stimulation, we treated aliquots of cells from one subject with a protease inhibitor cocktail with and without bethanechol (a muscarinic receptor agonist) at 100 and 400 µM and compared gene expression profiles. The protease inhibitors appeared to reduce cell stress. Pancreatic digestive enzymes and islet hormones were upregulated in both doses of bethanechol-treated cells compared with naïve cells. High-dose bethanechol appeared to be toxic and consistent with hyperstimulation. These studies demonstrate the feasibility of investigating human acinar cell physiology at the single-cell level and initial evidence that these cells retain responsiveness to agonist stimulation with predicted second messenger and transcriptomic responses.NEW & NOTEWORTHY We conducted single cell RNA sequencing on pancreas tissue from five individuals. We identified eleven unique cell clusters including a large population of dedifferentiated cells as well as two unique clusters of acinar cells, one of which appears to exist in a transitional state. We also examined the cellular response of pancreas tissue to stimulation and identified affected genes and pathways, including pancreatic digestive enzymes.

Neuroimmunology of cancer and associated symptomology.

Evolutionarily, the nervous system and immune cells have evolved to communicate with each other to control inflammation and host responses against injury. Recent findings in neuroimmune communication demonstrate that these mechanisms extend to cancer initiation and progression. Lymphoid structures and tumors, which are often associated with inflammatory infiltrate, are highly innervated by multiple nerve types (e.g. sympathetic, parasympathetic, sensory). Recent preclinical and clinical studies demonstrate that targeting the nervous system could be a therapeutic strategy to promote antitumor immunity while simultaneously reducing cancer-associated neurological symptoms, such as chronic pain, fatigue and cognitive impairment. Sympathetic nerve activity is associated with physiological or psychological stress, which can be induced by tumor development and cancer diagnosis. Targeting the stress response through suppression of sympathetic activity or activation of parasympathetic activity has been shown to drive activation of effector T cells and inhibition of myeloid-derived suppressor cells within the tumor. In addition, there is emerging evidence that sensory nerves may regulate tumor growth and metastasis by promoting or inhibiting immunosuppression in a tumor-type specific manner. Because neural effects are often tumor-type specific, further study is required to optimize clinical therapeutic strategies. This review examines the emerging evidence that neuroimmune communication can regulate antitumor immunity as well as contribute to development of cancer-related neurological symptoms.

Antenatal Risk Factors Associated with Spontaneous Intestinal Perforation in Preterm Infants Receiving Postnatal Indomethacin.

OBJECTIVE: To determine if antenatal variables affect the risk of spontaneous intestinal perforation (SIP) among preterm infants when prophylactic indomethacin is used. STUDY DESIGN: Retrospective case-control study of infants <29 weeks of gestational age between January 2010 and June 2018 at one hospital. SIP was defined as acute abdominal distension and pneumoperitoneum without signs of necrotizing enterocolitis at <14 days of life. Each case (n = 57) was matched with 2 controls (n = 114) for gestational age and birth year. Maternal and infant data were abstracted until the SIP or equivalent day for controls. Univariate analyses were followed by adjusted conditional logistic regressions and reported as OR and 95% CI. RESULTS: Mothers of cases were younger, more often delivering multiples (31% vs 14%, P = .007), and less abruptions (15% vs 29%, P = .045) but did not differ in intra-partum betamethasone, magnesium, or indomethacin use. Prophylactic indomethacin was given on day 1 to 99% of infants. SIP was associated with a shorter interval from last betamethasone dose to delivery (46 hours vs 96 hours, P = .01). Dopamine use (14% vs 4%, P = .02), volume expansion (23% vs 8%, P = .003), and high grade intraventricular hemorrhage (28% vs 8%, P = .0008) were related postnatal factors. The adjusted odds of SIP increased by 1% for each hour decrease between the last dose of betamethasone and delivery (OR 1.01, 95% CI 1.002-1.019) and with multiple births (OR 2.66, 95% CI 1.05-6.77). CONCLUSIONS: Antenatal betamethasone given shortly before delivery is associated with an increased risk of SIP. Potential interaction with medications such as postnatal indomethacin needs study.

Serum biomarkers for chronic pancreatitis pain patterns.

OBJECTIVES: Chronic pancreatitis (CP) is associated with debilitating refractory pain. Distinct subtypes of CP pain have been previously characterized based on severity (none, mild-moderate, severe) and temporal (none, intermittent, constant) nature of pain, but no mechanism-based tools are available to guide pain management. This exploratory study was designed to determine if potential pain biomarkers could be detected in patient serum and whether they associate with specific pain patterns. METHODS: Cytokines, chemokines, and peptides associated with nociception and pain were measured in legacy serum samples from CP patients (N = 99) enrolled in the North American Pancreatitis Studies. The unsupervised hierarchical cluster analysis was applied to cluster CP patients based on their biomarker profile. Classification and regression tree was used to assess whether these biomarkers can predict pain outcomes. RESULTS: The hierarchical cluster analysis revealed a subset of patients with predominantly constant, mild-moderate pain exhibited elevated interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-2 (IL-2), tumor necrosis factor alpha (TNFα), and monocyte chemoattractant protein-1 (MCP1) whereas patients with higher interleukin-4 (IL-4), interleukin-8 (IL-8) and calcitonin gene related peptide (CGRP) were more likely to have severe pain. Interestingly, analyses of each individual biomarker revealed that patients with constant pain had reduced circulating TNFα and fractalkine. Patients with severe pain exhibited a significant reduction in TNFα as well as trends towards lower levels of IL-6 and substance P. DISCUSSION: The observations from this study indicate that unique pain experiences within the chronic pancreatitis population can be associated with distinct biochemical signatures. These data indicate that further hypothesis-driven analyses combining biochemical measurements and detailed pain phenotyping could be used to develop precision approaches for pain management in patients with chronic pancreatitis.

Effects of a Home-Based Intervention on HIV Prevention Health Behaviors in Pregnant/Postpartum Kenyan Women: Estimating Moderating Effects of Depressive Symptoms.

We estimated effects of maternal depressive symptoms, utilizing the Patient Health Questionnaire-8 (PHQ-8), on women's HIV prevention behaviors in Migori County, Kenya. Pregnant women ≥ 18 years old, with gestational age of < 37 weeks, were randomized into standard care or three home visits (2 during pregnancy, 1 postpartum) promoting couple HIV testing and counseling (CHTC) and HIV prevention. Of 105 female participants, 37 (35.24%) reported depressive symptoms and 50 (47.62%) were HIV-positive. Three Poisson regressions with robust variance (univariable, multivariable, and multivariable with depressive symptoms/study arm interaction) were modeled for three outcomes: CHTC, infant HIV testing, health-seeking postpartum. In multivariable analysis with interaction, a moderating trend for the interaction between depressive symptoms and individual health-seeking was observed (p-value = 0.067). Women scoring ≤ 9 (n = 68) on the PHQ-8 and participating in home visits were 1.76 times more likely to participate in individual health-seeking compared to participants in standard care (ARR 1.76, 95% CI 1.17-2.66).

Colletotrichum fioriniae infecting invasive Japanese hop (Humulus scandens) in the United States.

Japanese hop (Humulus scandens) is a non-native, invasive plant that colonizes disturbed riparian areas throughout the eastern United States and Canada, forming dense, monocultural stands that displace native plant communities due to a high reproductive rate, rapid growth, climbing bines, and dense shading (Balogh and Dancza 2008). It is capable of serving as a reservoir for agronomically important plant pathogens, such as the Tomato spotted wilt virus and powdery mildew species that infect commercial hemp and hop fields (Yoon et al. 2018; Weldon et al. 2020). In the spring of 2016, diseased populations of H. scandens were observed along the Monocacy River in Frederick County, Maryland with severe chlorotic and necrotic leaf lesions. Symptomatic leaves were surface sterilized and placed in moist chambers at 25°C for sporulation. Sporulating acervuli, lacking setae, developed on irregular, tan necrotic leaf lesions following 7 to 12 days in a moist chamber (Figure 1). Conidia were hyaline, aseptate, smooth-walled, fusiform to cylindrical with both ends acute (Figure 1B). Conidia measured (n = 100) [L x W; Average (+ Std. Err), range]: 12.42 µm (± 0.10), 8.41 - 14.48 µm; x 3.91 µm (±0.03), 3.03 - 4.91 µm. Monoconidial fungal cultures were obtained by transferring conidia with a sterile glass needle to acidified potato dextrose agar and incubated at 25°C for 2 to 3 days. Based on phenotypic characteristics and conidial morphology and size, the pathogen appeared to belong to the Colletotrichum acutatum complex (Damm et al. 2012). Therefore, six loci (ITS, GADPH, CHS1, HIS3, ACT, and TUB2) were amplified and sequenced from a representative isolate, 16-008, for species characterization (GenBank accessions MW023070 to MW023075) (Damm et al. 2012). For the ITS region and ACT, GADPH, and CHS1 loci, isolate 16-008 was 100% identical to C. fioriniae and shared 99% similarity to TUB2 and HIS3 for multiple accessions of C. fioriniae in GenBank. Gene sequences were aligned, trimmed, concatenated, and analyzed against 32 reference strains, within the C. acutatum complex (Damm et al. 2012). Concatenated loci were used to generate a maximum likelihood phylogeny using W-IQ-TREE (Trifinopoulos et al. 2016). Results from the phylogenetic analysis demonstrated that isolate 16-008 was most genetically similar to C. fioriniae with a bootstrap support of 100% (Figure 2). Based on phenotypic and sequence analyses, isolate 16-008 was identified as C. fioriniae. Humulus scandens seedlings from Maryland (n = 3) were inoculated with a conidia suspension (107 conidia mL-1) with 0.125% Tween 20® and applied with an atomizer until runoff. Inoculated plants were placed in a dew chamber at 25°C for 2 days. Experimental plants were distributed in a mist tent at 25°C with 14 h of light and monitored for 2 weeks. Negative control plants (n = 2) were sprayed with a sterile 0.125% Tween 20® water solution. All inoculated plants were symptomatic by 12 days post inoculation. No symptoms were observed on the mock-inoculated plants. Symptoms were identical to disease field samples. Inoculations were repeated with the same results. Colletotrichum fioriniae was reisolated and confirmed from excised leaf lesions via ITS and ACT sequencing. To our knowledge, this is the first report of C. fioriniae naturally infecting H. scandens within the United States (Farr and Rossman 2020). Future studies will evaluate the host range of this isolate due to the species broad host range and the weed's extensive distribution.

One-year postpartum anthropometric outcomes in mothers and children in the LIFE-Moms lifestyle intervention clinical trials.

BACKGROUND/OBJECTIVES: Excess gestational weight gain (GWG) is a risk factor for maternal postpartum weight retention and excessive neonatal adiposity, especially in women with overweight or obesity. Whether lifestyle interventions to reduce excess GWG also reduce 12-month maternal postpartum weight retention and infant weight-for-length z score is unknown. Randomized controlled trials from the LIFE-Moms consortium investigated lifestyle interventions that began in pregnancy and tested whether there was benefit through 12 months on maternal postpartum weight retention (i.e., the difference in weight from early pregnancy to 12 months) and infant-weight-for-length z scores. SUBJECTS/METHODS: In LIFE-Moms, women (N = 1150; 14.1 weeks gestation at enrollment) with overweight or obesity were randomized within each of seven trials to lifestyle intervention or standard care. Individual participant data were combined and analyzed using generalized linear mixed models with trial entered as a random effect. The 12-month assessment was completed by 83% (959/1150) of women and 84% (961/1150) of infants. RESULTS: Compared with standard care, lifestyle intervention reduced postpartum weight retention (2.2 ± 7.0 vs. 0.7 ± 6.2 kg, respectively; difference of -1.6 kg (95% CI -2.5, -0.7; p = 0.0003); the intervention effect was mediated by reduction in excess GWG, which explained 22% of the effect on postpartum weight retention. Lifestyle intervention also significantly increased the odds (OR = 1.68 (95% CI, 1.26, 2.24)) and percentage of mothers (48.2% vs. 36.2%) at or below baseline weight at 12 months postpartum (yes/no) compared with standard care. There was no statistically significant treatment group effect on infant anthropometric outcomes at 12 months. CONCLUSIONS: Compared with standard care, lifestyle interventions initiated in pregnancy and focused on healthy eating, increased physical activity, and other behavioral strategies resulted in significantly less weight retention but similar infant anthropometric outcomes at 12 months postpartum in a large, diverse US population of women with overweight and obesity.

Pathways for HIV Prevention Behaviors Following a Home-Based Couples Intervention for Pregnant Women and Male Partners in Kenya.

Pregnancy is a time of heightened HIV risk, but also a phase when a couple can prioritize family health. We conducted secondary analysis of a home-based intervention in rural Kenya to explore couple-level adherence to HIV prevention behaviors. The intervention included health education, relationship-building skills, and Couples HIV Testing and Counseling. Pregnant women were randomized to the intervention (n = 64) or standard care (n = 63) along with male partners. Of 96 couples, 82 (85.0%) were followed to 3 months postpartum, when 31.0% of couples reported perfect adherence to HIV prevention. In logistic regression, intervention condition couples had three-fold higher odds of perfect adherence (AOR = 3.07, 95% CI = 1.01-9.32). A structural equation model found the intervention had moderate effects on couple communication, large effects on couple efficacy to take action around HIV, which in turn improved HIV prevention behaviors (CFI = 0.969; TLI = 0.955; RMSEA = 0.049). Strengthening couple communication and efficacy may help prevent the spread of HIV to infants or partners around the time of pregnancy.

Optogenetic Activation of Colon Epithelium of the Mouse Produces High-Frequency Bursting in Extrinsic Colon Afferents and Engages Visceromotor Responses.

Epithelial cells of the colon provide a vital interface between the internal environment (lumen of the colon) and colon parenchyma. To examine epithelial-neuronal signaling at this interface, we analyzed mice in which channelrhodopsin (ChR2) was targeted to either TRPV1-positive afferents or to villin-expressing colon epithelial cells. Expression of a ChR2-EYFP fusion protein was directed to either primary sensory neurons or to colon epithelial cells by crossing Ai32 mice with TRPV1-Cre or villin-Cre mice, respectively. An ex vivo preparation of the colon was used for single-fiber analysis of colon sensory afferents of the pelvic nerve. Afferents were characterized using previously described criteria as mucosal, muscular, muscular-mucosal, or serosal and then tested for blue light-induced activation. Light activation of colon epithelial cells produced robust firing of action potentials, similar to that elicited by physiologic stimulation (e.g., circumferential stretch), in 50.5% of colon afferents of mice homozygous for ChR2 expression. Light-induced activity could be reduced or abolished in most fibers using a cocktail of purinergic receptor blockers suggesting ATP release by the epithelium contributed to generation of sensory neuron action potentials. Using electromyographic recording of visceromotor responses we found that light stimulation of the colon epithelium evoked behavioral responses in Vil-ChR2 mice that was similar to that seen with balloon distension of the colon. These ex vivo and in vivo data indicate that light stimulation of colon epithelial cells alone, without added mechanical or chemical stimuli, can directly activate colon afferents and elicit behavioral responses.SIGNIFICANCE STATEMENT Abdominal pain that accompanies inflammatory diseases of the bowel is particularly vexing because it can occur without obvious changes in the structure or inflammatory condition of the colon. Pain reflects abnormal sensory neuron activity that may be controlled in part by release of substances from lining epithelial cells. In support of this mechanism we determined that blue-light stimulation of channelrhodopsin-expressing colon epithelial cells could evoke action potential firing in sensory neurons and produce changes in measures of behavioral sensitivity. Thus, activity of colon epithelial cells alone, without added mechanical or chemical stimuli, is sufficient to activate pain-sensing neurons.