Search

Prompt evaluation and genetic testing of patients who present with recurrent and recalcitrant warts, before onset of severe infection or myelodysplastic syndrome, leads to improved outcomes in patients with GATA2 deficiency.

Abstract It has previously been shown that the zinc-finger transcription factor Gata3 has dynamic expression within the inner ear throughout embryonic development and is essential for cochlear neurosensory development. However, the temporal window for which Gata3 is required for proper formation of the cochlear neurosensory epithelia remains unclear. To investigate the role of Gata3 in cochlear neurosensory development in the late prosensory stages, we used the Sox2-cre ERT2 mouse line to target and conditionally delete Gata3 at E11.5, a timepoint before cells have fully committed to a neurosensory fate. While the inner ears of Sox2-cre ERT2 : Gata3 f/f mice appear normal with no gross structural defects, the sensory cells in the organ of Corti are partially lost and disorganized in an increasing severity from base to apex. Additionally, spiral ganglion neurons display aberrant peripheral projections, including increased distances between radial bundles and disorganization upon reaching the organ of Corti. Furthermore, heterozygous Sox2-cre ERT2 : Gata3 f/+ mice show a reduced aberrant phenotype in comparison to the homozygous mutant, supporting the hypothesis that Gata3 is not only required for proper formation at the later proneurosensory stage, but also that a specific expression level of Gata3 is required. Therefore, this study provides evidence that Gata3 plays a time-sensitive and dose-dependent role in the development of sensory and neuronal cells in late proneurosensory stages.

During development the afferent neurons of the inner ear make precise wiring decisions in the hindbrain reflective of their topographic distribution in the periphery. This is critical for the formation of sensory maps capable of faithfully processing both auditory and vestibular input. Disorganized central projections of inner ear afferents in Fzd3 null mice indicate Wnt/PCP signaling is involved in this process and ear transplantation in Xenopus indicates that Fzd3 is necessary in the ear but not the hindbrain for proper afferent navigation. However, it remains unclear in which cell type of the inner ear Fzd3 expression is influencing the guidance of inner ear afferents to their proper synaptic targets in the hindbrain. We utilized Atoh1-cre and Neurod1-cre mouse lines to conditionally knockout Fzd3 within the mechanosensory hair cells of the organ of Corti and within the inner ear afferents, respectively. Following conditional deletion of Fzd3 within the hair cells, the central topographic distribution of inner ear afferents was maintained with no gross morphological defects. In contrast, conditional deletion of Fzd3 within inner ear afferents leads to central pathfinding defects of both cochlear and vestibular afferents. Here, we show that Fzd3 is acting in a cell autonomous manner within inner ear afferents to regulate central pathfinding within the hindbrain.

Abstract It is a critical time to reflect on the National Ecological Observatory Network (NEON) science to date as well as envision what research can be done right now with NEON (and other) data and what training is needed to enable a diverse user community. NEON became fully operational in May 2019 and has pivoted from planning and construction to operation and maintenance. In this overview, the history of and foundational thinking around NEON are discussed. A framework of open science is described with a discussion of how NEON can be situated as part of a larger data constellation—across existing networks and different suites of ecological measurements and sensors. Next, a synthesis of early NEON science, based on >100 existing publications, funded proposal efforts, and emergent science at the very first NEON Science Summit (hosted by Earth Lab at the University of Colorado Boulder in October 2019) is provided. Key questions that the ecology community will address with NEON data in the next 10 yr are outlined, from understanding drivers of biodiversity across spatial and temporal scales to defining complex feedback mechanisms in human–environmental systems. Last, the essential elements needed to engage and support a diverse and inclusive NEON user community are highlighted: training resources and tools that are openly available, funding for broad community engagement initiatives, and a mechanism to share and advertise those opportunities. NEON users require both the skills to work with NEON data and the ecological or environmental science domain knowledge to understand and interpret them. This paper synthesizes early directions in the community’s use of NEON data, and opportunities for the next 10 yr of NEON operations in emergent science themes, open science best practices, education and training, and community building.

Abstract Purpose Studies examining neurovascular coupling (NVC) require participants to refrain from exercise for 12–24 hours. However, there is a paucity of empirical evidence for this restriction. The objectives for this study were to delineate the time‐course recovery of NVC metrics following exercise and establish the NVC within‐ and between‐day reliability. Methods Nine participants completed a complex visual search paradigm to assess NVC via transcranial Doppler ultrasound of the posterior cerebral artery blood velocity (PCA). Measurements were performed prior to and throughout the 8‐hour recovery period following three randomized conditions: 45 minutes of moderate‐intensity exercise (at 50% heart‐rate reserve), 30 minutes high‐intensity intervals (10, 1‐minute intervals at 85% heart‐rate reserve), and control (30 minutes quiet rest). In each condition, baseline measures were collected at 8:00am with serial follow‐ups at hours zero, one, two, four, six, and eight. Results Area‐under‐the‐curve and time‐to‐peak PCA velocity during the visual search were attenuated at hour zero following high‐intensity intervals (all p 0.13). Conversely, baseline PCA velocity, peak PCA velocity, and the relative percent increase were not different following high‐intensity intervals compared to baseline (all p > 0.26). No NVC metrics differed from baseline following both moderate exercise and control conditions (all p > 0.24). The majority of the NVC parameters demonstrated high levels of reliability (intraclass correlation coefficient: >0.90). Conclusion Future NVC assessments can take place a minimum of one hour following exercise. Moreover, all metrics did not change across the control condition, therefore future studies using this methodology can reliably quantify NVC between 8:00am and 7:00 pm.

The mechanistic target of rapamycin (TOR) functions as an energy sensor and contributes to the control of glucose homeostasis. Here, the authors show that mTOR in the upper small intestine regulates hepatic glucose production and is required for the glucose lowering effect of metformin.

High protein diets are known to improve metabolic parameters including adiposity and glucose homeostasis. Here the authors demonstrate that preabsorptive upper small intestinal protein-sensing mechanisms mediated by peptide transporter 1 improve glucose homeostasis by inhibiting hepatic glucose production.

Mitochondria undergo dynamic changes to maintain function in eukaryotic cells. Insulin action in parallel regulates glucose homeostasis, but whether specific changes in mitochondrial dynamics alter insulin action and glucose homeostasis remains elusive. Here, we report that high-fat feeding in rodents incurred adaptive dynamic changes in mitochondria through an increase in mitochondrial fission in parallel to an activation of dynamin-related protein 1 (Drp1) in the dorsal vagal complex (DVC) of the brain. Direct inhibition of Drp1 negated high-fat-feeding-induced mitochondrial fission, endoplasmic reticulum (ER) stress, and insulin resistance in the DVC and subsequently restored hepatic glucose production regulation. Conversely, molecular activation of DVC Drp1 in healthy rodents was sufficient to induce DVC mitochondrial fission, ER stress, and insulin resistance. Together, these data illustrate that Drp1-dependent mitochondrial fission changes in the DVC regulate insulin action and suggest that targeting the Drp1-mitochondrial-dependent pathway in the brain may have therapeutic potential in insulin resistance.

Glycine sensing in the dorsal vagal complex (DVC) regulates hepatic glucose production in rodents. Here the authors show that pharmacological and molecular inhibition of glycine reuptake in the DVC potentiates NMDA receptors, and improves metabolic homeostasis in animal models of obesity and diabetes.

It is a critical time to reflect on the National Ecological Observatory Network (NEON) science to date as well as envision what research can be done right now with NEON (and other) data and what training is needed to enable a diverse user community. NEON became fully operational in May 2019 and has pivoted from planning and construction to operation and maintenance. In this overview, the history of and foundational thinking around NEON are discussed. A framework of open science is described with a discussion of how NEON can be situated as part of a larger data constellation—across existing networks and different suites of ecological measurements and sensors. Next, a synthesis of early NEON science, based on >100 existing publications, funded proposal efforts, and emergent science at the very first NEON Science Summit (hosted by Earth Lab at the University of Colorado Boulder in October 2019) is provided. Key questions that the ecology community will address with NEON data in the next 10 yr are outlined, from understanding drivers of biodiversity across spatial and temporal scales to defining complex feedback mechanisms in human–environmental systems. Last, the essential elements needed to engage and support a diverse and inclusive NEON user community are highlighted: training resources and tools that are openly available, funding for broad community engagement initiatives, and a mechanism to share and advertise those opportunities. NEON users require both the skills to work with NEON data and the ecological or environmental science domain knowledge to understand and interpret them. This paper synthesizes early directions in the community’s use of NEON data, and opportunities for the next 10 yr of NEON operations in emergent science themes, open science best practices, education and training, and community building.

This study investigated the impact of presentation formats on preservice teachers' ability to retain information along with their perceptions regarding subject matter and instructor's effectiveness. Participants were 79 preservice teachers in three sections of an elementary methods course. Each section received instruction using lecture and discussion accompanied by a different presentation format: black and white overhead transparencies, color overhead transparencies, and PowerPoint slides. Following treatment, participants responded to the Course Presentation Survey (CPS), a 7-item questionnaire developed to measure perceptions of presentation effectiveness, and completed a 10-item content quiz. Quantitative data from the CPS were analyzed using an analysis of variance while quiz scores were analyzed using an analysis of covariance with overall grade point average as the covariate. (Contains 3 tables.)

Abstract Background Patients with chronic low back (cLBP) pain report reduced physical function and ability to participate in social roles and are more likely to use opioid pain medications. While self-management interventions have been shown to support these patients, their effectiveness has been limited due to poor patient engagement. “Patient activation” encompasses the skills, knowledge, and motivation that a person has to manage their health. Supporting patient activation may improve the effectiveness of self-management for cLBP. Methods In this single-masked pilot study of adults with cLBP, patients were randomized to receive either no intervention (control) or 6 weekly sessions of an evidence-based web-based self-management program (SMP) with or without health behavior change counseling (HBCC) using motivational interviewing. Participants were assessed at baseline and at 12 and 26 weeks using the Patient Activation Measure, Oswestry Disability Index and PROMIS physical function, social role participation, and pain interference. We assessed acceptability and feasibility based on recruitment, session attendance, and follow-up. Results Of 187 individuals screened, 105 were eligible and 34 were randomized to control (n = 12), SMP (n = 4), or SMP + HBCC (n = 18). The population had 19 women, 22 patients married or living with significant other, 13 Black or African American patients, and 4 Hispanic or Latino patients. Participants had a mean (SD) Oswestry Disability Index score of 42 (12), moderate impairments in physical function (40 (6.6)) and social roles (45 (10)), and moderately severe pain interference (61 (6.7)). Of 22 participants receiving SMP sessions, 20 participated in at least 1, 15 participated in at least 3, and 7 participated in all 6 sessions. Loss to follow-up was 6 over the 26-week study. Participants in the SMP and SMP + HBCC groups had at least medium effect size improvements in Patient Activation Measures and small-to-medium effect size improvements in Oswestry Disability Index scores and physical function and large effect size improvement in social roles at 12 weeks. Improvements persisted in the SMP + HBCC group at 26 weeks. Conclusions A web-based SMP is acceptable and feasible in this population. Participants who received augmentation with HBCC had persistent improvements in health outcomes at 26 weeks. Trial Registration ClinicalTrials.gov Identifier NCT06236529 (2/1/2024 – retrospectively registered). Level of Evidence 3.

Many patients with cancer experience cancer-related cognitive decline (CRCD). Previous studies have shown that elevated S100β, a calcium-binding protein commonly found in glial cells, can exhibit neurotoxic effects, including disruption of the blood-brain barrier (BBB). We studied changes in S100β levels in patients with breast cancer receiving chemotherapy, and the relationship to changes in cognitive function. A total of 505 women with breast cancer (mean (sd) age; 53.4 (53.6)) and 336 age-matched controls without cancer (52.8 (10.3)) were included from a nationwide study as part of the National Cancer Institute Community Oncology Research Program (NCORP). Both groups provided blood samples and completed neurocognitive assessments within 7 days before the patients with breast cancer received their first chemotherapy dose (pre-chemotherapy; T1) and within 1 month of their last chemotherapy administration (post-chemotherapy; T2). Utilizing a linear mixed model, multivariate linear regressions, and Spearman rank correlations (rs), we investigated longitudinal changes in serum S100β concentrations and their relationships to changes in neurocognitive outcomes over time. We observed an increase in S100β for patients with breast cancer (p = 0.002), but not for controls without cancer over time (p = 0.683). Additionally, we identified subtle relationships between increases in serum S100β and worsening in cognitive performance on the Backward Counting test (rs = 0.11, p = 0.041) and self-reported FACT-Cog Perceived Cognitive Abilities (rs = −0.10, p = 0.025). Regression analyses adjusted for age, race, body-mass index (BMI), education, menopausal status, anxiety, and depression revealed a trend remained for the relationship of S100β with Backward Counting. In conclusion, we found that patients with breast cancer experience a significant increase in concentration of serum S100β over the course of chemotherapy. This increase is correlated with worsening in some neurocognitive outcomes from pre-to post-chemotherapy, with trending results remaining following adjustment for covariates.

Abstract Background Gestational diabetes mellitus (GDM) is a significant public health burden in Australia. Subsequent strain on healthcare systems is widespread and current models of care may not be adequate to provide optimal healthcare delivery. This study aimed to assess a current model of dietetic care with maternal and neonatal outcomes. Methods Hospital medical record data from The Women’s Hospital, Melbourne, for women with GDM (n = 1,185) (July 2105-May 2017) was retrospectively analysed. Adjusted linear and logistic regression were used to analyse associations between the number of dietitian consultations and maternal and neonatal health outcomes. Results Half of all women (50%) received two consultations with a dietitian. 19% of women received three or more consultations and of these women, almost twice as many were managed by medical nutrition therapy (MNT) and pharmacotherapy (66%) compared with MNT alone (34%). Higher odds of any maternal complication among women receiving 3 + consultations compared to those receiving zero (OR = 2.33 [95% CI: 1.23, 4.41], p = 0.009), one (OR = 1.80 [95% CI: 1.09, 2.98], p = 0.02), or two (OR = 1.65 [95% CI: 1.04, 2.60], p = 0.03) consultations were observed. Lower odds of infant admission to the Neonatal Intensive Care Unit (NICU) were observed among women receiving one (OR = 0.38 [95% CI: 0.18, 0.78], p = 0.008), two (OR = 0.37 [95% CI: 15 0.19, 0.71], p = 0.003), or three + consultations (OR = 0.43 [95% CI: 0.21, 0.88], p = 0.02), compared to no consultations. Conclusion The optimal schedule of dietitian consultations for women with GDM in Australia remains largely unclear. Alternate delivery of education for women with GDM such as telehealth and utilisation of digital platforms may assist relieving pressures on the healthcare system and ensure optimal care for women during pregnancy.

Abstract Background Food insecurity is a public health concern that has profound impact on physical and mental health, and on social well‐being. Pregnancy is a period in which food insecurity is likely to be particularly deleterious, due to the serious impact on both mother and child. Food insecurity is not routinely screened in antenatal healthcare settings, and the preferences of pregnant women regarding food insecurity screening and support are poorly understood. This study aimed to determine the views and preferences of food‐insecure pregnant women regarding food insecurity screening and support within antenatal healthcare. Methods This qualitative descriptive study used face‐to‐face semi‐structured interviews, conducted in February and March 2023, to gain the views of purposively sampled food‐insecure, pregnant women in Melbourne, Australia. Food insecurity was evidenced by an affirmative response to at least one of three assessment items in a screening questionnaire. Qualitative content analysis was conducted to summarise the views and preferences of women. Results Nineteen food‐insecure pregnant women were interviewed. Three themes were identified: (1) acceptability of being screened for food insecurity, (2) concerns about the consequences of disclosure and (3) preferences regarding food insecurity screening and supportive strategies that could be offered within an antenatal healthcare setting. Conclusion Women were accepting of food insecurity screening being conducted within routine healthcare. Women identified potential benefits of routine screening, such as feeling supported by their clinician to have a healthy pregnancy and less pressure to voluntarily ask for food assistance. Women gave suggestions for the implementation of food insecurity screening to optimise their healthcare experience, maintain their dignity and feel able to disclose within a safe and caring environment. These results indicate that food insecurity screening in the antenatal setting is likely to have support from pregnant women and is urgently needed in the interest of promoting optimal nutrition for women and children. Patient Contribution Pregnant women with lived experience of food insecurity were purposively sampled to obtain their insights regarding screening and support within a pregnancy healthcare setting. Member‐checking occurred following data collection, whereby all participants were offered the opportunity to review their interview transcript to ensure trustworthiness of the data.

Treatment modalities for breast cancer, including cyclophosphamide chemotherapy, have been associated with the development of cognitive decline (CRCD), which is characterized by impairments in memory, concentration, attention, and executive functions. We and others have identified a link between inflammation and decreased cognitive performance in patients with breast cancer receiving chemotherapy. In order to better understand the inflammation-associated molecular changes within the brain related to tumor alone or in combination with chemotherapy, we orthotopically implanted mouse mammary tumors (E0771) into female C57BL/6 mice and administered clinically relevant doses of cyclophosphamide and doxorubicin intravenously at weekly intervals for four weeks. We measured serum cytokines and markers of neuroinflammation at 48 h and up to one month post-treatment and tested memory using a reward-based delayed spatial alternation paradigm. We found that breast tumors and chemotherapy altered systemic inflammation and neuroinflammation. We further found that the presence of tumor and chemotherapy led to a decline in memory over time at the longest delay, when memory was the most taxed, compared to shorter delay times. These findings in a clinically relevant mouse model shed light on possible biomarkers for CRCD and add to the growing evidence that anti-inflammatory strategies have the potential to mitigate cancer- or treatment-related side effects.