Early progression during or after cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy indicates poor outcome with rescue protocols in dogs with multicentric lymphoma.

BACKGROUND: Dogs with lymphoma that fail cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (CHOP) before completion of their protocol are commonly thought to have poor long-term outcome, but no previous studies have evaluated the effect of early relapse on progression-free interval (PFI) or overall survival time (OST) for patients undergoing rescue chemotherapy. OBJECTIVE: Correlate rescue treatment outcomes in dogs with multicentric lymphoma with outcomes after 1st-line CHOP chemotherapy. METHODS: Data were collected from 6 previous retrospective or prospective studies in 187 dogs with multicentric lymphoma that received 1st-line CHOP chemotherapy and then received either lomustine (CCNU), L-asparaginase and prednisone (LAP), or rabacfosadine (RAB, Tanovea), with or without prednisone or L-asparaginase. RESULTS: The PFI after initiation of CHOP chemotherapy was significantly associated with response rate postprogression, PFI, and postrescue survival time (ST) for both rescue protocols. Immunophenotype (B- vs T-cell) was not significantly associated with response, PFI or OST for LAP but was significantly associated with response and PFI for RAB. CONCLUSION: Dogs that experience short PFI during or after 1st-line CHOP chemotherapy had lower response rates to rescue treatment, with shorter PFI and ST. Immunophenotype did not significantly affect outcome with LAP but was associated with PFI for RAB.

Unilateral Periorbital Swelling in a Pediatric Patient.

Infratemporal fossa (ITF) tumors are rare in children and may present with a variety of symptoms. Teratomas are neoplasms derived from the 3 germ layers and approximately 6% to 10% are within the head and neck. Our study discusses one of the first reported cases of teratoma in the ITF in a pediatric patient. A 3-year-old girl presents with 2 years of recurrent monthly left periorbital swelling accompanied by fevers, skin discoloration, and pain. Prior episodes were treated with antibiotics with incomplete resolution. Imaging revealed a cystic lesion centered in the ITF. She was taken for endoscopic endonasal biopsy of the lesion and had no complications. Pathology revealed a mature teratoma composed primarily of pancreatic tissue. Providers should consider masses such as teratoma in the differential for ITF tumors and periorbital edema unresponsive to typical treatment.

Age-related declines to serum prestin levels in humans.

Measurement of the motor protein prestin offers a novel approach to assessing outer hair cell (OHC) status using serological techniques. Motivated by our prior work showing reduced serum prestin levels in healthy young adults at-risk for noise damage, the current study examined serum prestin levels, measured from circulating blood, across the age span from 18 to 82 years old. Results suggest that serum prestin levels negatively correlate with age, with young adults having higher levels of circulating serum in the blood than older adults. Group-level analyses showed minimal differences in prestin levels between 18 and 29, 30-39, and 40-49 year olds, but significant reductions in the 50+ years-old age group compared to the three younger groups, even though all groups significantly differed from each other in audiometric thresholds and distortion product otoacoustic emissions signal-to-noise ratio. Serum prestin levels declined with increasing levels of hearing loss, with a statistically significant relationship emerging between prestin and low-frequency hearing thresholds (0.25-2 kHz) but a weaker non-significant relationship for high-frequency hearing thresholds (3-8 kHz). This differential pattern between low- and high- frequency thresholds is consistent with the basal-to-apical progression of OHC loss with age. Findings support the idea that serum prestin is the product of residual OHCs in the less age-affected apical regions. Moreover, when entered in a regression model with audiometric thresholds, age was a stronger predictor than pure tone hearing threshold level for predicting serum prestin levels.

A Home-Based Approach to Auditory Brainstem Response Measurement: Proof-of-Concept and Practical Guidelines.

Broad-scale neuroscientific investigations of diverse human populations are difficult to implement. This is because the primary neuroimaging methods (magnetic resonance imaging, electroencephalography [EEG]) historically have not been portable, and participants may be unable or unwilling to travel to test sites. Miniaturization of EEG technologies has now opened the door to neuroscientific fieldwork, allowing for easier access to under-represented populations. Recent efforts to conduct auditory neuroscience outside a laboratory setting are reviewed and then an in-home technique for recording auditory brainstem responses (ABRs) and frequency-following responses (FFRs) in a home setting is introduced. As a proof of concept, we have conducted two in-home electrophysiological studies: one in 27 children aged 6 to 16 years (13 with autism spectrum disorder) and another in 12 young adults aged 18 to 27 years, using portable electrophysiological equipment to record ABRs and FFRs to click and speech stimuli, spanning rural and urban and multiple homes and testers. We validate our fieldwork approach by presenting waveforms and data on latencies and signal-to-noise ratio. Our findings demonstrate the feasibility and utility of home-based ABR/FFR techniques, paving the course for larger fieldwork investigations of populations that are difficult to test or recruit. We conclude this tutorial with practical tips and guidelines for recording ABRs and FFRs in the field and discuss possible clinical and research applications of this approach.

Noise exposure levels predict blood levels of the inner ear protein prestin.

Serological biomarkers of inner ear proteins are a promising new approach for studying human hearing. Here, we focus on the serological measurement of prestin, a protein integral to a human's highly sensitive hearing, expressed in cochlear outer hair cells (OHCs). Building from recent nonhuman studies that associated noise-induced OHC trauma with reduced serum prestin levels, and studies suggesting subclinical hearing damage in humans regularly engaging in noisy activities, we investigated the relation between serum prestin levels and environmental noise levels in young adults with normal clinical audiograms. We measured prestin protein levels from circulating blood and collected noise level data multiple times over the course of the experiment using body-worn sound recorders. Results indicate that serum prestin levels have a negative relation with noise exposure: individuals with higher routine noise exposure levels tended to have lower prestin levels. Moreover, when grouping participants based on their risk for a clinically-significant noise-induced hearing loss, we found that prestin levels differed significantly between groups, even though behavioral hearing thresholds were similar. We discuss possible interpretations for our findings including whether lower serum levels may reflect subclinical levels of OHC damage, or possibly an adaptive, protective mechanism in which prestin expression is downregulated in response to loud environments.

The Effects of Delayed Cord Clamping on 12-Month Brain Myelin Content and Neurodevelopment: A Randomized Controlled Trial.

OBJECTIVE: This study aimed to determine if delayed cord clamping (DCC) affected brain myelin water volume fraction (VFm) and neurodevelopment in term infants. STUDY DESIGN: This was a single-blinded randomized controlled trial of healthy pregnant women with term singleton fetuses randomized at birth to either immediate cord clamping (ICC) (≤ 20 seconds) or DCC (≥ 5 minutes). Follow-up at 12 months of age consisted of blood work for serum iron indices and lead levels, a nonsedated magnetic resonance imaging (MRI), followed within the week by neurodevelopmental testing. RESULTS: At birth, 73 women were randomized into one of two groups: ICC (the usual practice) or DCC (the intervention). At 12 months, among 58 active participants, 41 (80%) had usable MRIs. There were no differences between the two groups on maternal or infant demographic variables. At 12 months, infants who had DCC had increased white matter brain growth in regions localized within the right and left internal capsules, the right parietal, occipital, and prefrontal cortex. Gender exerted no difference on any variables. Developmental testing (Mullen Scales of Early Learning, nonverbal, and verbal composite scores) was not significantly different between the two groups. CONCLUSION: At 12 months of age, infants who received DCC had greater myelin content in important brain regions involved in motor function, visual/spatial, and sensory processing. A placental transfusion at birth appeared to increase myelin content in the early developing brain. KEY POINTS: · DCC resulted in higher hematocrits in newborn period.. · DCC appears to increase myelin at 12 months.. · Gender did not influence study outcomes..

Reliability of Serological Prestin Levels in Humans and its Relation to Otoacoustic Emissions, a Functional Measure of Outer Hair Cells.

OBJECTIVES: Serological biomarkers, common to many areas of medicine, have the potential to inform on the health of the human body and to give early warning of risk of compromised function or illness before symptoms are experienced. Serological measurement of prestin, a motor protein uniquely produced and expressed in outer hair cells, has recently been identified as a potential biomarker to inform on the health of the cochlea. Before any test can be introduced into the clinical toolkit, the reproducibility of the measurement when repeated in the same subject must be considered. The primary objective of this study is to outline the test-retest reliability estimates and normative ranges for serological prestin in healthy young adults with normal hearing. In addition, we examine the relation between serum prestin levels and otoacoustic emissions (OAEs) to compare this OHC-specific protein to the most common measure of OHC function currently used in hearing assessments. DESIGN: We measured prestin levels serologically from circulating blood in 34 young adults (18 to 24 years old) with clinically normal pure-tone audiometric averages at five different timepoints up to six months apart (average intervals between measurements ranged from <1 week to 7 weeks apart). To guide future studies of clinical populations, we present the standard error of the measurement, reference normative values, and multiple measures of reliability. Additionally, we measured transient evoked OAEs at the same five timepoints and used correlation coefficients to examine the relation between OAEs and prestin levels (pg/mL). RESULTS: Serum prestin levels demonstrated good to excellent reliability between and across the five different time points, with correlation coefficients and intraclass correlations >0.8. Across sessions, the average serum prestin level was 250.20 pg/mL, with a standard error of measurement of 7.28 pg/mL. Moreover, positive correlations (generally weak to moderate) were found between prestin levels and OAE magnitudes and signal-to-noise ratios. CONCLUSIONS: Findings characterize serum prestin in healthy young adults with normal hearing and provide initial normative data that may be critical to interpreting results from individuals with sensorineural hearing loss. Our results demonstrate reliability of serum prestin levels in a sample of normal-hearing young adults across five test sessions up to 6 months apart, paving the way for testing larger samples to more accurately estimate test-retest standards for clinical protocols, including those involving serial monitoring. The positive correlations between serum prestin and OAE levels, although weak to moderate, reinforce that the source of serum prestin is likely the outer hair cells in the inner ear, but also that serum prestin and OAEs each may also index aspects of biologic function not common to the other.

Increasing the amplitude of intrinsic theta in the human brain.

In a mouse study we found increased myelination of pathways surrounding the anterior cingulate cortex (ACC) following stimulation near the theta rhythm (4-8 Hz), and evidence that this change in connectivity reduced behavioral anxiety. We cannot use the optogenetic methods with humans that were used in our mouse studies. This paper examines whether it is possible to enhance intrinsic theta amplitudes in humans using less invasive methods. The first experiment compares electrical, auditory and biofeedback as methods for increasing intrinsic theta rhythm amplitudes in the Anterior Cingulate Cortex (ACC). These methods are used alone or in conjunction with a task designed to activate the same area. The results favor using electrical stimulation in conjunction with a task targeting this region. Stimulating the ACC increases intrinsic theta more in this area than in a control area distant from the site of stimulation, suggesting some degree of localization of the stimulation. In Experiment 2, we employed electrical stimulation with the electrodes common to each person, or with electrodes selected from an individual head model. We targeted the ACC or Motor Cortex (PMC). At baseline, intrinsic theta is higher in the ACC than the PMC. In both areas, theta can be increased in amplitude by electrical stimulation plus task. In the PMC, theta levels during stimulation plus task are not significantly higher than during task alone. There is no significant difference between generic and individual electrodes. We discuss steps needed to determine whether we can use the electrical stimulation + task to improve the connectivity of white matter in different brain areas.

A review of inherited cancer susceptibility syndromes.

Inherited cancer syndromes are caused by genetic mutations that place patients at an increased risk for developing cancer. Although most cancers are not caused by genetic inheritance, clinicians must understand these syndromes and be able to recognize their common characteristics. A thorough family history and identification of common patterns as well as specific clinical signs and symptoms can help with early recognition. This article describes symptoms of the more common cancer syndromes, including hereditary breast and ovarian cancer, Li-Fraumeni, Lynch, familial adenomatous polyposis, retinoblastoma, multiple endocrine neoplasia, and von Hippel-Lindau. Important patient education regarding genetic testing also is covered.

Comparisons of Auditory Brainstem Responses Between a Laboratory and Simulated Home Environment.

Purpose Miniaturization of digital technologies has created new opportunities for remote health care and neuroscientific fieldwork. The current study assesses comparisons between in-home auditory brainstem response (ABR) recordings and recordings obtained in a traditional lab setting. Method Click-evoked and speech-evoked ABRs were recorded in 12 normal-hearing, young adult participants over three test sessions in (a) a shielded sound booth within a research lab, (b) a simulated home environment, and (c) the research lab once more. The same single-family house was used for all home testing. Results Analyses of ABR latencies, a common clinical metric, showed high repeatability between the home and lab environments across both the click-evoked and speech-evoked ABRs. Like ABR latencies, response consistency and signal-to-noise ratio (SNR) were robust both in the lab and in the home and did not show significant differences between locations, although variability between the home and lab was higher than latencies, with two participants influencing this lower repeatability between locations. Response consistency and SNR also patterned together, with a trend for higher SNRs to pair with more consistent responses in both the home and lab environments. Conclusions Our findings demonstrate the feasibility of obtaining high-quality ABR recordings within a simulated home environment that closely approximate those recorded in a more traditional recording environment. This line of work may open doors to greater accessibility to underserved clinical and research populations.

The Veterans Health Administration Whole Health Model of Care: Early Implementation and Utilization at a Large Healthcare System.

INTRODUCTION: The U.S. Veterans Health Administration (VHA) is changing the way it provides healthcare to a model known as Whole Health (WH). The aim is to shift from a primarily medical/disease-oriented system to a model that focuses on health promotion and disease prevention; utilizes personalized, proactive, and patient-driven care; and emphasizes the use of complementary and integrative health. This investigation aimed to examine referral and utilization patterns in early implementation at tertiary care VHA medical care system. Specific aims were to evaluate (1) referral patterns, (2) initial treatment engagement, and (3) continuity of treatment engagement. MATERIALS AND METHODS: This is an institutional review board-approved, retrospective study of the first 561 veterans referred to WH programming in the first 20 months of implementation. Data analyses included a chi-square goodness of fit to compare demographics of veterans who were referred to WH Services with those of local patient population. At this facility, WH offers services in three tracks (General WH, Mindfulness Center [MC], and WH Nutrition), which offer unique services to veterans. A chi-square test for independence was conducted to analyze differences in initial engagement among the WH components, in referrals and retention among WH components by time period, and in demographics or diagnoses among self-referred or veterans referred by a consult. Finally, a regression model was used to assess for predictive factors that might influence continuity of treatment engagement across all the WH tracks. RESULTS: Key findings indicated potential implementation challenges including disproportionate numbers of referrals from clinical services; poor initial and ongoing treatment engagement; and older, male, and non-service-connected Veterans being less likely to be referred. CONCLUSION: Implementation of the WH model of care has the potential to transform the way VHA delivers healthcare and improve the health and lives of veterans. However, a shift of this magnitude is likely to face challenges during implementation. This article reports on initial barriers to implementation, which can guide implementation at other sites as well as future investigations. Further research is needed to replicate these results as well as to determine underlying causal factors. However, if replicated, these results indicate that successful implementation of WH, or similar models of care, will require extensive efforts focused on outreach to, and education of, facility providers and certain patient demographic groups. Finally, efforts will be required to enhance treatment engagement.

Veterans' interests, perceptions, and use of mindfulness.

OBJECTIVE: Mindfulness-based interventions are an evidence-based approach utilized in health care. There is developing evidence for effective use with military Veterans. However, little is known about Veterans' view of mindfulness. This study aims to understand their interests, perceptions, and use of mindfulness to enhance educational outreach and treatment engagement. METHODS: A cross-sectional study was conducted across the Veterans Health Administration in Salt Lake City, UT by administering a questionnaire to military Veterans. The questionnaire included the following themes: (1) demographics and respondents' mindfulness practice; (2) respondents' perceptions and beliefs about mindfulness; and (3) respondents' knowledge and interest in learning about mindfulness. RESULTS: In all, 185 military Veterans were surveyed; 30% practiced mindfulness in the past year, mainly for stress, posttraumatic stress disorder, sleep, and depression. Over 75% who practiced reported perceived benefit. Veterans rarely reported negative beliefs about mindfulness; 56% perceived an understanding of mindfulness and 46% were aware of Veterans Health Administration mindfulness offerings. In all, 55% were interested in learning about mindfulness, 58% were interested in learning how it could help, and 43% were interested in combining mindfulness with a pleasurable activity. CONCLUSION: Educational engagement approaches should be directed toward the benefits of mindfulness practice with minimal need to address negative beliefs. Outreach including education, with an experiential component, about mindfulness classes, availability of evening and weekend classes, individual sessions, and virtual offerings into Veteran's homes, may enhance engagement in mindfulness-based interventions. Mindfulness-based interventions that combine mindfulness training with an experiential pleasurable activity may be one mechanism to enhance treatment engagement.

The Association Between Mindfulness and Postoperative Pain: A Prospective Cohort Study of Gynecologic Oncology Patients Undergoing Minimally Invasive Hysterectomy.

STUDY OBJECTIVE: To describe the association between preoperative dispositional mindfulness (the personality trait of being mindful) and postoperative pain in gynecologic oncology patients undergoing minimally invasive hysterectomy. DESIGN: Prospective cohort study. SETTING: University-affiliated teaching hospital. PATIENTS: Gynecologic oncology patients (n = 126) planning minimally invasive hysterectomy. INTERVENTIONS: Minimally invasive hysterectomy. MEASUREMENTS AND MAIN RESULTS: Baseline mindfulness was assessed at the preoperative visit using the Five Facet Mindfulness Questionnaire (FFMQ). Postoperative pain and opioid usage were evaluated via chart review and surveys at postoperative visits at 1 to 2 weeks and 4 to 6 weeks. Higher baseline mindfulness was correlated with lower postoperative pain as measured by both the average and highest numeric pain scores during the inpatient stay (r = -.23, p = .020; r = -.21, p = .034). At the initial postoperative visit, pain score was also inversely correlated with preoperative mindfulness score (r = -.26, p = .008). This relationship was not observed at the final postoperative visit (r = -.08, p = .406). Pre-operative mindfulness and opioid usage were also inversely associated, though this relationship did not reach statistical significance (r = -.18, p = .066). CONCLUSION: Mindfulness was previously shown to be a promising intervention for chronic pain treatment. Our study demonstrates that higher preoperative dispositional mindfulness is associated with more favorable postoperative pain outcomes, including lower pain scores but not lower opioid consumption. This relationship provides an opportunity to target the modifiable personality characteristic of mindfulness, to reduce postoperative pain in patients following gynecologic surgery.

Opioid use after minimally invasive hysterectomy in gynecologic oncology patients.

OBJECTIVES: To quantify, and identify predictors of, post-discharge opioid use in gynecologic oncology patients undergoing minimally invasive hysterectomy (MIH). METHODS: For this prospective cohort study, gynecologic oncology patients planning to undergo MIH were recruited at a single institution. Post-operative opioid usage was evaluated via chart review and surveys at 1-2-week and 4-6-week post-operative visits. Opioids are converted to oral morphine milligram equivalents (MME) for standardization. Descriptive statistics and modified Poisson regression were used to quantify opioid requirements and evaluate predictors of post-discharge opioid use respectively. RESULTS: One hundred eighteen eligible women underwent MIH. Of these, 108 had complete data at both follow-up timepoints. Malignancy was present in 79% of cases, 71% of which were endometrial cancer. Most surgeries were laparoscopic (73%). Median hospital stay was 1 night (IQR 1-1). Inpatients received a median of 30.75 MME (IQR 7.5-52.5 MME). Twenty-three women (21.3%) used no opioids while inpatient. At the 1-2-week follow-up median usage was 6 pills of 5 mg oxycodone, or 45 MME (IQR 0-15.5 pills). After complete follow-up, median post-discharge usage was 10 pills, or 75 MME (IQR 0-22.5 pills) and 36 participants (33.33%) used no opioids after hospital discharge. The median prescription was for 30 pills (range 10-60). Above median inpatient opioid use was associated with an increased risk of above median opioid usage after hospital discharge (RR 2.31, 95% CI 1.38-3.87) on multivariable analysis. CONCLUSIONS: In this cohort, opioids were overprescribed relative to use. Inpatient use was the strongest predictor of post-discharge opioid use. More restrictive, and personalized, opioid prescribing practices may be a pathway to reduce opioid misuse and diversion. PRéCIS: Opioids were overprescribed by a factor of three to gynecologic oncology patients, whose inpatient opioid requirement predicted post-discharge opioid needs after minimally invasive hysterectomy.

Effects of Delayed Cord Clamping on 4-Month Ferritin Levels, Brain Myelin Content, and Neurodevelopment: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether placental transfusion influences brain myelination at 4 months of age. STUDY DESIGN: A partially blinded, randomized controlled trial was conducted at a level III maternity hospital in the US. Seventy-three healthy term pregnant women and their singleton fetuses were randomized to either delayed umbilical cord clamping (DCC, >5 minutes) or immediate clamping (ICC, <20 seconds). At 4 months of age, blood was drawn for ferritin levels. Neurodevelopmental testing (Mullen Scales of Early Learning) was administered, and brain myelin content was measured with magnetic resonance imaging. Correlations between myelin content and ferritin levels and group-wise DCC vs ICC brain myelin content were completed. RESULTS: In the DCC and ICC groups, clamping time was 172 ± 188 seconds vs 28 ± 76 seconds (P < .002), respectively; the 48-hour hematocrit was 57.6% vs 53.1% (P < .01). At 4 months, infants with DCC had significantly greater ferritin levels (96.4 vs 65.3 ng/dL, P = .03). There was a positive relationship between ferritin and myelin content. Infants randomized to the DCC group had greater myelin content in the internal capsule and other early maturing brain regions associated with motor, visual, and sensory processing/function. No differences were seen between groups in the Mullen testing. CONCLUSION: At 4 months, infants born at term receiving DCC had greater ferritin levels and increased brain myelin in areas important for early life functional development. Endowment of iron-rich red blood cells obtained through DCC may offer a longitudinal advantage for early white matter development. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01620008.

The Church Bridge Project: An Academic-Community Perspective of a Church-Based Weight Management Pilot Intervention among Young Adult African Americans.

BACKGROUND: Churches are effective community partners and settings to address weight management among African Americans. There is limited information on the use of churches to reach young adult populations and church collaborations with primary care clinics. OBJECTIVES: The Church Bridge Project represents a community-academic partnership that presents the recruitment process of a church-based weight management intervention and describes baseline data of participants recruited from churches and primary care providers. We also discuss research contributions, challenges and limitations, study applicability, and practice implications from an academic and community perspective. METHODS: Church leaders were involved in the entire research process. The theory-driven intervention included 12 diabetes prevention program-adapted education and motivational interviewing (MI)-guided sessions. Participants were recruited through primary care providers and church leaders. Demographics, medical and weight history, stage of change for weight loss, social support, and self-efficacy for diet and physical activity, weight, and girth circumferences were measured. Baseline descriptive data were analyzed. RESULTS: Of 64 potential participants, 42 (65.6%) were enrolled in the study and 16 (25.0%) completed baseline data collection. No participants were recruited through primary care providers. Recruited participants were similar to the target population except for being all obese and mostly female. The mean ± SD age of participants was 34.31 ± 8.86 years with most reporting having more than a high school education (n = 14 [87.5%]), individual yearly income of less than $59,000 (n = 12 [75.0%]), and been married or living with a partner (n = 9 [56.3%]). Most reported a history of hypertension and an immediate family history of diabetes and hypertension. Most participants were classified as class III obesity. CONCLUSIONS: Young adults and primary care providers are difficult to engage in church-based interventions. Church leaders were comfortable with a collaborate model for decision making, but not an empower model. Churches remain a successful method to reach African Americans; however, more research is needed to motivate young adults to participate in health intervention research.

Alterations in the placental methylome with maternal obesity and evidence for metabolic regulation.

The inflammatory and metabolic derangements of obesity in pregnant women generate an adverse intrauterine environment, increase pregnancy complications and adverse fetal outcomes and program the fetus for obesity and metabolic syndrome in later life. We hypothesized that epigenetic modifications in placenta including altered DNA methylation/hydroxymethylation may mediate these effects. Term placental villous tissue was collected following cesarean section from lean (prepregnancy BMI<25) or obese (BMI>30) women. Genomic DNA was isolated, methylated and hydroxymethylated DNA immunoprecipitated and hybridized to the NimbleGen 2.1M human DNA methylation array. Intermediate metabolites in placental tissues were measured by HPLC-ESI-MS, ascorbate levels by reverse phase HPLC and gene expression by RT-PCR. Differentially methylated and hydroxymethylated regions occurred across the genome, with a 21% increase in methylated but a 31% decrease in hydroxymethylated regions in obese vs lean groups. Whereas increased methylation and decreased methylation was evident around transcription start sites of multiple genes in the GH/CSH and PSG gene clusters on chromosomes 17 and 19 in other areas there was no relationship. Increased methylation was associated with decreased expression only for some genes in these clusters. Biological pathway analysis revealed the 262 genes which showed reciprocal differential methylation/ hydroxymethylation were enriched for pregnancy, immune response and cell adhesion-linked processes. We found a negative relationship for maternal BMI but a positive relationship for ascorbate with α-ketoglutarate a metabolite that regulates ten eleven translocase (TET) which mediates DNA methylation. We provide evidence for the obese maternal metabolic milieu being linked to an altered DNA methylome that may affect placental gene expression in relation to adverse outcomes.

Alternative pathways for Escherichia coli biofilm formation revealed by sRNA overproduction.

Small regulatory RNAs have major roles in many regulatory circuits in Escherichia coli and other bacteria, including the transition from planktonic to biofilm growth. We tested Hfq-dependent sRNAs in E. coli for their ability, when overproduced, to inhibit or stimulate biofilm formation, in two different growth media. We identify two mutually exclusive pathways for biofilm formation. In LB, PgaA, encoding an adhesion export protein, played a critical role; biofilm was independent of the general stress factor RpoS or CsgD, regulator of curli and other biofilm genes. The PgaA-dependent pathway was stimulated upon overproduction of DsrA, via negative regulation of H-NS, or of GadY, likely by titration of CsrA. In yeast extract casamino acids (YESCA) media, biofilm was dependent on RpoS and CsgD, but independent of PgaA; RpoS appears to indirectly negatively regulate the PgaA-dependent pathway in YESCA medium. Deletions of most sRNAs had very little effect on biofilm, although deletion of hfq, encoding an RNA chaperone, was defective in both LB and YESCA. Deletion of ArcZ, a small RNA activator of RpoS, decreased biofilm in YESCA; only a portion of this defect could be bypassed by overproduction of RpoS. Overall, sRNAs highlight different pathways to biofilm formation.

The ecology of population dispersal: Modeling alternative basin-plateau foraging strategies to explain the Numic expansion.

OBJECTIVES: The expansion of Numic speaking populations into the Great Basin required individuals to adapt to a relatively unproductive landscape. Researchers have proposed numerous social and subsistence strategies to explain how and why these settlers were able to replace any established populations, including private property and intensive plant processing. Here we evaluate these hypotheses and propose a new strategy involving the use of landscape fire to increase resource encounter rates. METHODS: Implementing a novel, spatially explicit, multi-scalar prey choice model, we examine how individual decisions approximating each alternative strategy (private property, anthropogenic fire, and intensive plant processing) would aggregate at the patch and band level to confer an overall benefit to this colonizing population. Analysis relies on experimental data reporting resource profitability and abundance, ecological data on the historic distribution of vegetation patches, and ethnohistoric data on the distribution of Numic bands. RESULTS: Model results show that while resource privatization and landscape fires produce a substantial advantage, intensified plant processing garners the greatest benefit. The relative benefits of alternative strategies vary significantly across ecological patches resulting in variation across ethnographic band ranges. Combined, a Numic strategy including all three alternatives would substantially increase subsistence yields. CONCLUSIONS: The application of a strategy set that includes landscape fire, privatization and intensified processing of seeds and nuts, explains why the Numa were able to outcompete local populations. This approach provides a framework to help explain how individual decisions can result in such population replacement events throughout human history.