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BACKGROUND AND PURPOSE: Falls that occur while walking have been associated with an increased risk of hip fracture in elderly people. This study's purpose was to describe movement characteristics in older adults that serve as indicators of difficulty in turning while walking. SUBJECTS: Three groups were assessed: young adults who had no difficulty in turning (age range=20-30 years, n=20) (YNDT group), elderly adults who had no difficulty in turning (age range=65-87 years, n=15) (ENDT group), and elderly adults who had difficulty in turning (age range=69-92 years, n=15) (EDT group). METHODS: All subjects were videotaped performing a self-paced 180-degree turn during the Timed 'Up & Go' Test. Movement characteristics of each group were identified. Four characteristics were used to identify difficulty in turning: (1) the type of turn, (2) the number of steps taken during the turn, (3) the time taken to accomplish the turn, (4) and staggering during the turn. RESULTS: In general, the EDT group took more steps during the turn and more time to accomplish the turn than the YNDT and ENDT groups. Although the only turning strategy used by the YNDT group was a pivot type of turn, there was an almost total absence of a pivot type of turn in the EDT group. No differences were found among the groups on the staggering item, yet the EDT group was the only group in which staggering was present. We believe these changes observed in the 4 characteristics only in the EDT group are indicators of difficulty in turning while walking. CONCLUSION AND DISCUSSION: These indicators of difficulty may be useful for the early identification of individuals aged 65 years or older who are having difficulty in turning and may well serve as the basis for the development of a scale for difficulty in turning in older adults. Preliminary findings indicate the need for further study into the reliability, validity, and sensitivity of measurements obtained with such a scale. [ABSTRACT FROM AUTHOR]

Despite a significant decrease in the number of prescriptions for opioids, the opioid crisis continues, fueled in large part by the availability of the phenylpiperidine mu opioid receptor (MOR) agonist fentanyl. In contrast, the number of prescriptions for and the off-label use of gabapentinoids (gabapentin and pregabalin) has increased dramatically, with gabapentinoids commonly detected in opioid overdose victims. Although gabapentinoids can decrease the potency of the opioid receptor antagonist naloxone to reverse heroin-induced hypoventilation in male rats, the specificity and nature of interaction between gabapentinoids and MOR agonists and any potential sex difference in those interactions are not well characterized. Gabapentinoids were studied in female and male rats discriminating fentanyl (0.0032 mg/kg, i.p.) or cocaine (3.2 mg/kg, i.p.). Alone, neither gabapentin nor pregabalin significantly increased fentanyl- or cocaine-appropriate responding. In rats discriminating fentanyl, each gabapentinoid dose-dependently shifted the fentanyl and heroin discrimination dose-effect functions to the left, whereas naloxone dose-dependently shifted the fentanyl and heroin discrimination dose-effect functions to the right. Each gabapentinoid (100 mg/kg) significantly decreased the potency of naloxone to antagonize the discriminative stimulus effect of fentanyl or heroin. In contrast, each gabapentinoid dose-dependently shifted the cocaine and d -methamphetamine discrimination dose-effect functions to the right. There were no significant sex differences in this study. These results suggest that gabapentinoids impact the misuse of opioids, the co-use of opioids and stimulant drugs, and the increasing number of overdose deaths in individuals using opioids, stimulant drugs, and gabapentinoids in mixtures. SIGNIFICANCE STATEMENT: The number of prescriptions for and the off-label use of gabapentinoids (gabapentin and pregabalin) has increased dramatically, with gabapentinoids commonly detected in opioid overdose victims. This study reports that in rats gabapentinoids increase the potency of fentanyl and heroin to produce discriminative stimulus effects while decreasing the potency of naloxone to antagonize those effects of fentanyl and heroin. These results can help guide policies for regulating gabapentinoids and treating opioid misuse and overdose., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

Methods to measure chromatin contacts at genomic regions bound by histone modifications or proteins are important tools to investigate chromatin organization. However, such methods do not capture the possible involvement of other epigenomic features such as G-quadruplex DNA secondary structures (G4s). To bridge this gap, we introduce ViCAR (viewpoint HiCAR), for the direct antibody-based capture of chromatin interactions at folded G4s. Through ViCAR, we showcase the first G4-3D interaction landscape. Using histone marks, we also demonstrate how ViCAR improves on earlier approaches yielding increased signal-to-noise. ViCAR is a practical and powerful tool to explore epigenetic marks and 3D genome interactomes., (© 2024. The Author(s).)

Interdisciplinary teams are on the rise as scientists attempt to address complex environmental issues. While the benefits of team science approaches are clear, researchers often struggle with its implementation, particularly for new team members. The challenges of large projects often weigh on the most vulnerable members of a team: trainees, including undergraduate students, graduate students, and post-doctoral researchers. Trainees on big projects have to navigate their role on the team, with learning project policies, procedures, and goals, all while also training in key scientific tasks such as co-authoring papers. To address these challenges, we created and participated in a project-specific, graduate-level team science course. The purposes of this course were to: (1) introduce students to the goals of the project, (2) build trainees' understanding of how big projects operate, and (3) allow trainees to explore how their research interests dovetailed with the overall project. Additionally, trainees received training regarding: (1) diversity, equity & inclusion, (2) giving and receiving feedback, and (3) effective communication. Onboarding through the team science course cultivated psychological safety and a collaborative student community across disciplines and institutions. Thus, we recommend a team science course for onboarding students to big projects to help students establish the skills necessary for collaborative research. Project-based team science classes can benefit student advancement, enhance the productivity of the project, and accelerate the discovery of solutions to ecological issues by building community, establishing a shared project vocabulary, and building a workforce with collaborative skills to better answer ecological research questions., Competing Interests: The authors declare no conflicts of interest with regard to this work., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Brief interventions for lifestyle behaviour change are effective health promotion interventions. Primary care settings, including pharmacies, are the most frequently visited healthcare facilities and are well placed to provide brief health interventions. However, despite the evidence-based and policy guidance, barriers to brief interventions have limited their implementation., Objectives: This study aimed to explore the usability and acceptability of HealthEir, a blended model with digital, print, and communication elements designed to support the delivery of brief health-promoting interventions in pharmacy practice., Methods: Usability tests using a think aloud protocol and set tasks (to assess usability) and semi-structured interviews (to assess acceptability) were conducted with fifteen patients and twelve pharmacists. Usability data were analysed deductively using Nielsen's five quality components of usability as a framework. Acceptability data were analysed using inductive thematic analysis., Findings: All participants found HealthEir straightforward to use and completed the required tasks without assistance. A small number of patient and pharmacist participants identified opportunity for improvement of the digital element. Acceptability was also high, with individual comments from participants identifying opportunity for improvements to HealthEir, and two patients identifying privacy or safety concerns. The majority of comments regarding acceptability reflected wider social and cultural challenges such as perceptions of the roles of pharmacists and pharmacies and the low priority of preventative health interventions., Conclusion: HealthEir has been demonstrated to be a usable and acceptable support that has the potential to overcome barriers to delivery of brief interventions in pharmacies. Usability and acceptability testing identified minor changes that may further improve its design prior to piloting and implementation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Despite an increasing prevalence of gabapentinoids (gabapentin and pregabalin) in opioid overdose deaths, little research has evaluated potentially harmful interactions between gabapentinoids and opioids. This study sought to determine the effects of gabapentinoids on the ventilatory depressive effects of heroin and their reversal by naloxone. Rats were given gabapentin, pregabalin, or saline prior to receiving increasing doses of heroin while ventilation was monitored using whole-body plethysmography. In some sessions naloxone was administered following the largest dose of heroin. The primary outcomes of this study were minute volume and Pause. Heroin dose-dependently reduced minute volume and increased Pause. Administration of naloxone dose-dependently reversed the effects of heroin on ventilation. Gabapentinoids did not alter the ventilatory depressive effects of heroin alone but reduced the potency of naloxone to reverse heroin-induced ventilatory depression. These preliminary findings emphasize the need for further research evaluating interactions between gabapentinoids and opioids related to substance misuse and overdose., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

G-quadruplexes (G4s) are four-stranded DNA secondary structures that occur in the human genome and play key roles in transcription, replication, and genome stability. G4-specific molecular probes are of vital importance to elucidate the structure and function of G4s. The scFv antibody BG4 has been a widely used G4 probe but has various limitations, including relatively poor in vitro expression and the inability to be expressed intracellularly to interrogate G4s in live cells. To address these considerations, we describe herein the development of SG4, a camelid heavy-chain-only derived nanobody that was selected against the human Myc DNA G4 structure. SG4 exhibits low nanomolar affinity for a wide range of folded G4 structures in vitro. We employed AlphaFold combined with molecular dynamics simulations to construct a molecular model for the G4-nanobody interaction. The structural model accurately explains the role of key amino acids and K d measurements of SG4 mutants, including arginine-to-alanine point mutations that dramatically diminish G4 binding affinity. Importantly, predicted amino acid-G4 interactions were subsequently confirmed experimentally by biophysical measurements. We demonstrate that the nanobody can be expressed intracellularly and used to image endogenous G4 structures in live cells. We also use the SG4 protein to positionally map G4s in situ and also on fixed chromatin. SG4 is a valuable, new tool for G4 detection and mapping in cells.

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A defining characteristic of individuals diagnosed with alcohol use disorder (AUD) is that negative outcomes related to drinking do not lead them to reduce their alcohol use. In rodent models of AUD, this characteristic has been studied by adding the bitter tastant quinine to an ethanol solution. In this study, we extended this approach to a nonhuman primate model in which the ability of quinine to decrease the choice of a 4% ethanol solution vs. water was measured. Five adult female rhesus monkeys with 7.3 years of experience drinking ethanol were given access to a 4% ethanol solution and water for 3 h per day. When ethanol choice was stable, a single quinine concentration (0.03-5.6 g /L) was added to the ethanol solution for 1 day until a quinine concentration-effect curve was generated. After determining the quinine concentration that reduced ethanol choice by half (the quinine EC 50 ), the relative reinforcing strength of ethanol was manipulated by adding quinine or sucrose to the water alternative depending on the monkey's baseline choice. Adding quinine to ethanol produced a concentration-dependent decrease in ethanol choice and intake. Importantly, water intake increased, indicating an effect on response allocation rather than simply a decrease in fluid consumption. Consistent with this conclusion, the addition of quinine or sucrose to the water alternative resulted in predictable increases and decreases, respectively, in ethanol choice. These studies establish a model of punishment of ethanol choice in nonhuman primates that can be used to understand the contextual, biologic and pharmacologic factors that influence sensitivity to the punishment of alcohol drinking., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Drug overdose deaths involving synthetic opioids, primarily fentanyl, have risen dramatically over the past decade and are currently the driving force of the opioid epidemic in the United States. Fentanyl analogs with greater potency than fentanyl (e.g., carfentanil) pose serious risk to public health. Although fentanyl analogs are primarily encountered by humans as constituents of a mixture of drugs, research has primarily evaluated the effects of these drugs alone. The present study characterized interactions between mu opioid receptor agonists in seven male Sprague-Dawley rats trained to discriminate 10 μ g/kg fentanyl from saline while responding under a fixed-ratio 10 schedule of food presentation. Dose-effect curves were determined for each drug alone and in binary mixtures (fentanyl:heroin, fentanyl:carfentanil, and heroin:carfentanil) at fixed-dose ratios of 3:1, 1:1, and 1:3 relative to the ED 50 for each drug when given alone. Dose addition analyses were used to determine the nature of the drug-drug interaction for each mixture. Additive interactions were observed for all binary mixtures at each fixed dose ratio, except the 1:3 fentanyl:carfentanil mixture, which exhibited supra-additive effects at the 80% effect level. These results suggest a lack of a significant interaction between the discriminative stimulus effects of these mu opioid receptor agonists at the doses tested in this study. Future studies expanding these findings to the respiratory depressant effects of these drugs are of significant importance to rule out possible interactions directly relevant to opioid overdose that occur at doses much larger than those tested in this study. SIGNIFICANCE STATEMENT: In the United States, drug overdose deaths involving synthetic opioids, primarily fentanyls including superpotent fentanyl analogs (e.g., carfentanil), have increased 12-fold over the past decade. Although previous studies have evaluated the effects of carfentanil alone, fentanyl analogs are encountered by humans as a mixture with other drugs; this study determined the effects of mixtures of carfentanil and other opioids (fentanyl and heroin) to characterize interactions between these drugs that might contribute to their apparent increased lethality in humans., (Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.)

The establishment of cell identity during embryonic development involves the activation of specific gene expression programmes and is underpinned by epigenetic factors including DNA methylation and histone post-translational modifications. G-quadruplexes are four-stranded DNA secondary structures (G4s) that have been implicated in transcriptional regulation and cancer. Here, we show that G4s are key genomic structural features linked to cellular differentiation. We find that G4s are highly abundant in human embryonic stem cells and are lost during lineage specification. G4s are prevalent in enhancers and promoters. G4s that are found in common between embryonic and downstream lineages are tightly linked to transcriptional stabilisation of genes involved in essential cellular functions as well as transitions in the histone post-translational modification landscape. Furthermore, the application of small molecules that stabilise G4s causes a delay in stem cell differentiation, keeping cells in a more pluripotent-like state. Collectively, our data highlight G4s as important epigenetic features that are coupled to stem cell pluripotency and differentiation., (© 2022. The Author(s).)

Despite numerous benefits, traditional Pulmonary Rehabilitation (PR) as a resource remains underutilized in chronic lung disease. Less than 3% of eligible candidates for PR attend one or more sessions after hospitalization due to many barriers, including the ongoing COVID-19 pandemic. Emerging alternative models of PR delivery such as home-based PR, tele-rehabilitation, web-based PR, or hybrid models could help address these barriers. Numerous studies have tested the feasibility, safety, and efficacy of these methods, but there is wide variability across studies and methods. We conducted a literature review to help determine if these alternative delivery methods watered down the effectiveness of PR. To evaluate the effectiveness of remotely based PR, the authors performed a literature search for randomized controlled trials (RCTs), cohort studies, and case series using PubMed, CINAHL, and Medline to identify relevant articles through 1 May 2021. Twenty-six applicable studies were found in which 11 compared tele-rehabilitation to conventional clinic-based PR; 11 evaluated tele-rehabilitation using the patient's baseline status as control; and four compared tele-rehabilitation to no rehabilitation. Despite the different technologies used across studies, tele-rehabilitation was found to be both a feasible and an efficacious option for select patients with lung disease. Outcomes across these studies demonstrated similar benefits to traditional PR programs. Thus the existing data does not show that remotely based PR waters down the effectiveness of conventional PR. Use of remotely based PR is a feasible and effective option to deliver PR, especially for patients with significant barriers to conventional clinic-based PR. Additional, well-conducted RCTs are needed to answer the questions regarding its efficacy, safety, cost-effectiveness and who, among patients with COPD and other lung diseases, will derive the maximum benefit.

Proximity labeling provides a powerful in vivo tool to characterize the proteome of subcellular structures and the interactome of specific proteins. The nematode Caenorhabditis elegans is one of the most intensely studied organisms in biology, offering many advantages for biochemistry. Using the highly active biotin ligase TurboID, we optimize here a proximity labeling protocol for C. elegans. An advantage of TurboID is that biotin's high affinity for streptavidin means biotin-labeled proteins can be affinity-purified under harsh denaturing conditions. By combining extensive sonication with aggressive denaturation using SDS and urea, we achieved near-complete solubilization of worm proteins. We then used this protocol to characterize the proteomes of the worm gut, muscle, skin, and nervous system. Neurons are among the smallest C. elegans cells. To probe the method's sensitivity, we expressed TurboID exclusively in the two AFD neurons and showed that the protocol could identify known and previously unknown proteins expressed selectively in AFD. The active zones of synapses are composed of a protein matrix that is difficult to solubilize and purify. To test if our protocol could solubilize active zone proteins, we knocked TurboID into the endogenous elks-1 gene, which encodes a presynaptic active zone protein. We identified many known ELKS-1-interacting active zone proteins, as well as previously uncharacterized synaptic proteins. Versatile vectors and the inherent advantages of using C. elegans, including fast growth and the ability to rapidly make and functionally test knock-ins, make proximity labeling a valuable addition to the armory of this model organism., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A significant number of deaths caused by opioids involve fentanyl and/or one of its very potent analogs (e.g., carfentanil). Some clinical reports suggest larger doses of opioid receptor antagonists may be required to reverse the effects of carfentanil compared with other opioid receptor agonists, although this has not been examined extensively in vivo. The current study compared the discriminative stimulus effects of fentanyl, carfentanil, and heroin, and their antagonism by naltrexone., Methods: Eight male Sprague-Dawley rats were trained to discriminate 10.0 μg/kg fentanyl from saline while responding under a fixed-ratio 10 schedule of food presentation. Dose-effect curves were determined for the opioid receptor agonists fentanyl (1.0-32.0 μg/kg), carfentanil (0.1-3.2 μg/kg), and heroin (10.0-320.0 μg/kg), then redetermined following a 15-minute pretreatment with 0.1 mg/kg naltrexone., Results: Fentanyl, carfentanil, and heroin dose-dependently increased responding on the fentanyl-associated lever and decreased the rate of lever pressing. Carfentanil and heroin were approximately 10-fold more and less potent, respectively, than fentanyl at eliciting >80 % responding on the fentanyl-associated lever. Pretreatment with 0.1 mg/kg naltrexone resulted in a significant rightward shift in the fentanyl and heroin but not carfentanil dose-effect curves., Conclusions: Differences in the effectiveness of naltrexone to attenuate the discriminative stimulus effects of carfentanil, compared with fentanyl and heroin, suggest that there may be differences in how carfentanil exerts its discriminative stimulus effects compared with other opioids. Further evaluation is needed of potential pharmacological and behavioral differences between carfentanil and other opioids, particularly in the context of toxicity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Besides pro-inflammatory roles, the ancient cytokine interleukin-17 (IL-17) modulates neural circuit function. We investigate IL-17 signaling in neurons, and the extent it can alter organismal phenotypes. We combine immunoprecipitation and mass spectrometry to biochemically characterize endogenous signaling complexes that function downstream of IL-17 receptors in C. elegans neurons. We identify the paracaspase MALT-1 as a critical output of the pathway. MALT1 mediates signaling from many immune receptors in mammals, but was not previously implicated in IL-17 signaling or nervous system function. C. elegans MALT-1 forms a complex with homologs of Act1 and IRAK and appears to function both as a scaffold and a protease. MALT-1 is expressed broadly in the C. elegans nervous system, and neuronal IL-17-MALT-1 signaling regulates multiple phenotypes, including escape behavior, associative learning, immunity and longevity. Our data suggest MALT1 has an ancient role modulating neural circuit function downstream of IL-17 to remodel physiology and behavior.

Neuroblastoma is the most common extracranial solid tumor of childhood and accounts for 15% of all pediatric cancer-related deaths. New therapies are needed to improve outcomes for children with high-risk and relapsed tumors. Inhibitors of the RET kinase and the RAS-MAPK pathway have previously been shown to be effective against neuroblastoma, suggesting that combined inhibition may have increased efficacy. RXDX-105 is a small molecule inhibitor of multiple kinases, including the RET and BRAF kinases. We found that treatment of neuroblastoma cells with RXDX-105 resulted in a significant decrease in cell viability and proliferation in vitro and in tumor growth and tumor vascularity in vivo . Treatment with RXDX-105 inhibited RET phosphorylation and phosphorylation of the MEK and ERK kinases in neuroblastoma cells and xenograft tumors, and RXDX-105 treatment induced both apoptosis and cell cycle arrest. RXDX-105 also showed enhanced efficacy in combination with 13- cis -retinoic acid, which is currently a component of maintenance therapy for children with high-risk neuroblastoma. Our results demonstrate that RXDX-105 shows promise as a novel therapeutic agent for children with high-risk and relapsed neuroblastoma., Competing Interests: CONFLICTS OF INTEREST This study was supported by Ignyta, Inc. who provided study drug (to PEZ)., (Copyright: © 2019 Flynn et al.)

Alcohol use disorder (AUD) persists as a devastating public health problem; widely effective pharmacological treatments are needed. Evidence from rodent models suggests that stimulating brain receptors for the neuropeptide nociceptin/orphanin FQ (NOP) can decrease ethanol drinking. We characterized the effects of the mu opioid peptide (MOP) receptor agonist buprenorphine and the buprenorphine analog (2S)-2-[(5R,6R,7R,14S)-N-cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6 methoxymorphinan-7-yl]-3,3-dimethylpentan-2-ol (BU08028), which stimulates MOP and NOP receptors, in a translational nonhuman primate model of AUD. Rhesus monkeys drank a 4% ethanol solution 6 h per day, 5 days per week via an operant behavioral panel in their home cages. To assess behavioral selectivity, monkeys responded via a photo-optic switch to earn food pellets. After characterizing the acute effects of BU08028 (0.001-0.01 mg/kg, i.m.) and buprenorphine (0.003-0.056 mg/kg, i.m.), the drugs were administered chronically using a model of pharmacotherapy assessment that incorporates clinical aspects of AUD and treatment. Acutely, both drugs decreased ethanol drinking at doses that did not affect food-maintained responding. During chronic treatment, effects of BU08028 and buprenorphine were maintained for several weeks without development of tolerance or emergence of adverse effects. BU08028 was ~0.5 and 1.0 log units more potent in acute and chronic studies, respectively. The selective NOP receptor agonist SCH 221510 also selectively decreased ethanol intakes when given acutely (0.03-1.0 mg/kg, i.m.), whereas the MOP antagonist naltrexone (1.7-5.6 mg/kg, i.m.) decreased both ethanol intake and food pellets delivered. These data demonstrate that bifunctional MOP/NOP agonists, which may have therapeutic advantages to MOP-selective drugs, can decrease alcohol drinking in nonhuman primates.

Background and Objectives: Carnoy's fixation and compression represents a novel technique to enhance lymph node evaluation and accuracy of staging after colorectal cancer resection., Methods: This study was performed in all adults undergoing colorectal cancer operations by Kaiser Permanente surgeons at two separate facilities. Patients were assigned to either location based upon surgeon and patient availability. One group of patients had their lymph nodes examined with current standard manual technique (MT). The other group had their specimens fixed with Carnoy's solution and then compressed (CT) to assess for lymph nodes., Results: A total of 157 patients were enrolled. Seventy-eight patient specimens underwent MT and 79 patient specimens underwent the new compression technique (CT). CT resulted in a significant increase in total lymph node yield per specimen (37.6 ± 18.5 nodes with CT vs 18.9 ± 8.8 nodes with MT; P < 0.0001). CT also resulted in sufficient lymph node sampling (>12 nodes) in all 79 patients in the group compared with 13 of 78 patients (17%) with an insufficient lymph node evaluation in the MT group ( P = 0.0002)., Conclusion: This study demonstrated that Carnoy's fixation with compression can significantly increase lymph node yields in colorectal cancer specimens and allow for a higher rate of adequate lymph node sampling., (© 2019 Wiley Periodicals, Inc.)

Mammary gland morphogenesis begins during fetal development but expansion of the mammary tree occurs postnatally in response to hormones, growth factors and extracellular matrix. Hyaluronan (HA) is an extracellular matrix polysaccharide that has been shown to modulate growth factor-induced branching in culture. Neither the physiological relevance of HA to mammary gland morphogenesis nor the role that HA receptors play in these responses are currently well understood. We show that HA synthase (HAS2) is expressed in both ductal epithelia and stromal cells but HA primarily accumulates in the stroma. HA accumulation and expression of the HA receptors CD44 and RHAMM are highest during gestation when gland remodeling, lateral branch infilling and lobulo-alveoli formation is active. Molecular weight analyses show that approximately 98% of HA at all stages of morphogenesis is >300kDa. Low levels of 7-114kDa HA fragments are also detected and in particular the accumulation of 7-21kDa HA fragments are significantly higher during gestation than other morphogenetic stages (p<0.05). Using these in vivo results as a guide, in culture analyses of mammary epithelial cell lines (EpH4 and NMuMG) were performed to determine the roles of high molecular weight, 7-21kDa (10kDa MWavg) and HA receptors in EGF-induced branching morphogenesis. Results of these assays show that while HA synthesis is required for branching and 10kDa HA fragments strongly stimulate branching, the activity of HA decreases with increasing molecular weight and 500kDa HA strongly inhibits this morphogenetic process. The response to 10kDa HA requires RHAMM function and genetic deletion of RHAMM transiently blunts lateral branching in vivo. Collectively, these results reveal distinct roles for HA polymer size in modulating growth factor induced mammary gland branching and implicates these polymers in both the expansion and sculpting of the mammary tree during gestation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Human papillomavirus (HPV), and the related, cervical intraepithelial neoplasia (CIN), are common yet poorly understood physical conditions. The diagnosis of HPV often elicits shame and guilt, which in turn may undermine psychological and physical health. The current study compared shame and guilt responses to diagnosis among two groups: women diagnosed with HPV/CIN and women diagnosed with Epstein-Barr Virus (EBV/IM). Eighty women recently diagnosed with HPV/CIN or EBV/IM completed measures of shame- and guilt-proneness, shame and guilt following diagnosis, and disease knowledge including prevalence estimates (HPV and EBV, respectively). HPV/CIN (vs. EBV/IM) predicted more diagnosis-related shame and guilt. Estimates of high prevalence interacted with diagnosis and shame-proneness to predict diagnosis-related shame. Simple slope analyses indicated that in women with HPV/CIN reporting low-to-average shame-proneness, high prevalence estimates reduced diagnosis-related shame; however, women high in shame-proneness experienced high diagnosis-related shame regardless of more accurate prevalence estimates. Women high in shame-proneness appear to be particularly vulnerable to HPV-related shame even when they are aware that it is very common.

Background: Little empirical evidence exists on the effectiveness of using Twitter as a two-way communication tool for public health practice, such as Twitter chats., Objective: We analyzed whether Twitter chats facilitate engagement in two-way communications between public health entities and their audience. We also describe how to measure two-way communications, incoming and outgoing mentions, between users in a protocol using free and publicly available tools (Symplur, OpenRefine, and Gephi)., Methods: We used a mixed-methods approach, social network analysis, and content analysis. The study population comprised individuals and organizations participating or who were mentioned in the first #LiveFitNOLA chat, during a 75-min period on March 5, 2015, from 12:00 PM to 1:15 PM Central Time. We assessed audience engagement in two-way communications with two metrics: engagement ratio and return on engagement (ROE)., Results: The #LiveFitNOLA chat had 744 tweets and 66 participants with an average of 11 tweets per participant. The resulting network had 134 network members and 474 engagements. The engagement ratios and ROEs for the #LiveFitNOLA organizers were 1:1, 40% (13/32) (@TulanePRC) and 2:1, -40% (-25/63) (@FitNOLA). Content analysis showed information sharing (63.9%, 314/491) and health information (27.9%, 137/491) as the most salient theme and sub-theme, respectively., Conclusions: Our findings suggest Twitter chats facilitate audience engagement in two-way communications between public health entities and their audience. The #LiveFitNOLA organizers' engagement ratios and ROEs indicated a moderate level of engagement with their audience. The practical significance of the engagement ratio and ROE depends on the audience, context, scope, scale, and goal of a Twitter chat or other organized hashtag-based communications on Twitter., (©Kristina M Rabarison, Merriah A Croston, Naomi K Englar, Connie L Bish, Shelbi M Flynn, Carolyn C Johnson. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 08.06.2017.)

The neural circuitry mediating fear extinction has been increasingly well studied and delineated. The rodent infralimbic subregion (IL) of the ventromedial prefrontal cortex (vmPFC) has been found to promote extinction, whereas the prelimbic cortex (PL) demonstrates an opposing, pro-fear, function. Studies employing in vivo electrophysiological recordings have observed that while increased IL single-unit firing and bursting predicts robust extinction retrieval, increased PL firing can correlate with sustained fear and poor extinction. These relationships between single-unit firing and extinction do not hold under all experimental conditions, however. In the current study, we further investigated the relationship between vmPFC and PL single-unit firing and extinction using inbred mouse models of intact (C57BL/6J, B6) and deficient (129S1/SvImJ, S1) extinction strains. Simultaneous single-unit recordings were made in the PL and vmPFC (encompassing IL) as B6 and S1 mice performed extinction training and retrieval. Impaired extinction retrieval in S1 mice was associated with elevated PL single-unit firing, as compared to firing in extinguishing B6 mice, consistent with the hypothesized pro-fear contribution of PL. Analysis of local field potentials also revealed significantly higher gamma power in the PL of S1 than B6 mice during extinction training and retrieval. In the vmPFC, impaired extinction in S1 mice was also associated with exaggerated single-unit firing, relative to B6 mice. This is in apparent contradiction to evidence that IL activity promotes extinction, but could reflect a (failed) compensatory effort by the vmPFC to mitigate fear-promoting activity in other regions, such as the PL or amygdala. In support of this hypothesis, augmenting IL activity via direct infusion of the GABAA receptor antagonist picrotoxin rescued impaired extinction retrieval in S1 mice. Chronic fluoxetine treatment produced modest reductions in fear during extinction retrieval and increased the number of Zif268-labeled cells in layer II of IL, but failed to increase vmPFC single-unit firing. Collectively, these findings further support the important contribution these cortical regions play in determining the balance between robust extinction on the one hand, and sustained fear on the other. Elucidating the precise nature of these roles could help inform understanding of the pathophysiology of fear-related anxiety disorders., (Published by Elsevier Inc.)

Elevated levels of fluoride (F(-)) in groundwaters of granitic and basaltic terrains pose a major environmental problem and are affecting millions of people all over the world. Hydroxyapatite (HA) has been shown to be a strong sorbent for F(-); however, low permeability of synthetic HA results in poor sorption efficiency. Here we provide a novel method of synthesizing nano- to micrometer sized HA on the surfaces of granular limestone to improve the sorption efficiency of the HA-based filter. Our experiments with granular limestone (38-63, 125-500 μm) and dissolved PO4(3-) (0.5-5.3 mM) as a function of pH (6-8) and temperature (25-80 °C) indicated rapid formation of nano- to micrometer sized HA crystals on granular limestone with the maximum surface coverage at lower pH and in the presence of multiple additions of aqueous PO4(3-). The HA crystal morphology varied with the above variables. The sorption kinetics and magnitude of F(-) sorption by HA-coated-fine limestone are comparable to those of pure HA, and the F(-) levels dropped to below the World Health Organization's drinking water limit of 79 μM for F(-) concentrations commonly encountered in contaminated potable waters, suggesting that these materials could be used as effective filters. Fluorine XANES spectra of synthetic HA reacted with F(-) suggest that the mode of sorption is through the formation of fluoridated-HA or fluorapatite at low F(-) levels and fluorite at high F(-) loadings.

Objective: Approximately 10% of convicted homicide perpetrators in England and Wales have symptoms of mental illness at the time of homicide. The prevalence among perpetrators of adult domestic homicide is unclear., Methods: The study was a consecutive case series of all convicted adult domestic homicide perpetrators in England and Wales between 1997 and 2008. Sociodemographic, clinical, and offense characteristics were gathered from the United Kingdom Home Office, the Police National Computer, psychiatric court reports, and, for psychiatric patients, questionnaires completed by supervising clinicians., Results: A total of 1,180 perpetrators were convicted of intimate partner homicide, and 251 were convicted of homicide of an adult family member. Fourteen percent of perpetrators of intimate partner homicide and 23% of perpetrators of adult family homicide had been in contact with mental health services in the year before the offense; 20% of intimate partner homicide perpetrators and 34% of adult family homicide perpetrators had symptoms of mental illness at the time of offense. Perpetrators with symptoms of mental illness at the time of offense were less likely than perpetrators without symptoms to have previous violence convictions or history of alcohol abuse., Conclusions: A significant minority of adult domestic homicide perpetrators had symptoms of mental illness at the time of the homicide. Most perpetrators, including those with mental illnesses, were not in contact with mental health services in the year before the offense. Risk reduction could be achieved through initiatives that encourage individuals with mental health problems to access mental health services and that develop closer interagency working, including between mental health services, police, social services, and domestic violence services.

Background: Most child victims of homicide are killed by a parent or step-parent. This large population study provides a contemporary and detailed description of filicide perpetrators. We examined the relationship between filicide and mental illness at the time of the offence, and care received from mental health services in the past., Method: All filicide and filicide-suicide cases in England and Wales (1997-2006) were drawn from a national index of homicide perpetrators. Data on people in contact with mental health services were obtained via a questionnaire from mental health teams. Additional clinical information was collected from psychiatric reports., Results: 6144 people were convicted of homicide, 297 were filicides, and 45 cases were filicide-suicides. 195 (66%) perpetrators were fathers. Mothers were more likely than fathers to have a history of mental disorder (66% v 27%) and symptoms at the time of the offence (53% v 23%), most often affective disorder. 17% of mothers had schizophrenia or other delusional disorders. Overall 8% had schizophrenia. 37% were mentally ill at the time of the offence. 20% had previously been in contact with mental health services, 12% within a year of the offence., Conclusion: In the majority of cases, mental illness was not a feature of filicide. However, young mothers and parents with severe mental illness, especially affective and personality disorder who are providing care for children, require careful monitoring by mental health and other support services. Identifying risk factors for filicide requires further research.

Alcoholism is frequently co-morbid with post-traumatic stress disorder, but it is unclear how alcohol affects the neural circuits mediating recovery from trauma. We found that chronic intermittent ethanol (CIE) impaired fear extinction and remodeled the dendritic arbor of medial prefrontal cortical (mPFC) neurons in mice. CIE impaired extinction encoding by infralimbic mPFC neurons in vivo and functionally downregulated burst-mediating NMDA GluN1 receptors. These findings suggest that alcohol may increase risk for trauma-related anxiety disorders by disrupting mPFC-mediated extinction of fear.

Repetitive thought (RT) - attentive, prolonged, or frequent thought about oneself and one's world - plays an important role in many models of psychological and physical ill health (e.g., rumination and worry), as well as models of recovery and well-being (e.g., processing and reminiscing). In these models, repetitive thought is typically treated as stable or trait-like. In contrast, episodic RT reflects what people have "on their minds" at a particular point in time. In four studies, young women (N=94), college students (N=166), first-year law students (N=73), and older adults (N=174) described their episodic RT, which was then rated for qualities including valence, purpose, and theme. Episodic RT valence was associated with mood and depressive symptoms both between (Studies 1-4) and within people (Studies 3-4), and it mediated the effects of dispositional coping through emotional approach (Study 1). The effect of episodic RT valence in turn was moderated by other properties of episodic RT, including purpose, "trait" valence, and theme (Studies 1-4). The study of episodic RT complements that of trait RT and allows for observations of how RT and psychological adjustment change in concert and in context, as well as examining how the RT qualities that are not reflected in trait measures affect adjustment.

Background: The rise in homicides by those with serious mental illness is of concern, although this increase may not be continuing., Aims: To examine rates of mental illness among homicide perpetrators., Method: A national consecutive case series of homicide perpetrators in England and Wales from 1997 to 2006. Rates of mental disorder were based on data from psychiatric reports, contact with psychiatric services, diminished responsibility verdict and hospital disposal., Results: Of the 5884 homicides notified to the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness between 1997 and 2006, the number of homicide perpetrators with schizophrenia increased at a rate of 4% per year, those with psychotic symptoms at the time of the offence increased by 6% per year. The number of verdicts of diminished responsibility decreased but no change was found in the number of perpetrators receiving a hospital order disposal. The likeliest explanation for the rise in homicide by people with psychosis is the misuse of drugs and/or alcohol, which our data show increased at a similar magnitude to homicides by those with psychotic symptoms. However, we are unable to demonstrate a causal association. Although the Poisson regression provides evidence of an upward trend in homicide by people with serious mental illness between 1997 and 2006, the number of homicides fell in the final 2 years of data collection, so these findings should be treated with caution., Conclusions: There appears to be a concomitant increase in drug misuse over the period, which may account for this rise in homicide. However, an increase in the number of people in contact with mental health services may suggest that access to mental health services is improving. Previous studies have used court verdicts such as diminished responsibility as a proxy measure of mental disorder. Our data indicate that this does not reflect accurately the prevalence of mental disorder in this population.

Dickeya dadantii is a plant-pathogenic enterobacterium responsible for the soft rot disease of many plants of economic importance. We present here the sequence of strain 3937, a strain widely used as a model system for research on the molecular biology and pathogenicity of this group of bacteria.

Using the advances in computing power, software and hardware technologies, virtual reality (VR), and gaming applications have the potential to address clinical challenges for a range of disabilities. VR-based games can potentially provide the ability to assess and augment cognitive and motor rehabilitation under a range of stimulus conditions that are not easily controllable and quantifiable in the real world. This article discusses an approach for maximizing function and participation for those aging with and into a disability by combining task-specific training with advances in VR and gaming technologies to enable positive behavioral modifications for independence in the home and community. There is potential for the use of VR and game applications for rehabilitating, maintaining, and enhancing those processes that are affected by aging with and into disability, particularly the need to attain a balance in the interplay between sensorimotor function and cognitive demands and to reap the benefits of task-specific training and regular physical activity and exercise.

Objective: To examine paired reflex depression changes post 20-minute bout each of 2 training environments: stationary bicycle ergometer training (bicycle training) and treadmill with body weight support and manual assistance (locomotor training)., Design: Pretest-posttest repeated-measures., Setting: Locomotor laboratory., Participants: Motor incomplete SCI (n=12; mean, 44+/-16y); noninjured subjects (n=11; mean, 30.8+/-8.3y)., Intervention: All subjects received each type of training on 2 separate days., Main Outcome Measure: Paired reflex depression at different interstimulus intervals (10 s, 1 s, 500 ms, 200 ms, and 100 ms) was measured before and after both types of training., Results: (1) Depression was significantly less post-SCI compared with noninjured subjects at all interstimulus intervals and (2) post-SCI at 100-millisecond interstimulus interval: reflex depression significantly increased postbicycle training in all SCI subjects and in the chronic and spastic subgroups (P<.05)., Conclusions: Phase-dependent regulation of reflex excitability, essential to normal locomotion, coordinated by pre- and postsynaptic inhibitory processes (convergent action of descending and segmental inputs onto spinal circuits) is impaired post-SCI. Paired reflex depression provides a quantitative assay of inhibitory processes contributing to phase-dependent changes in reflex excitability. Because bicycle training normalized reflex depression, we propose that bicycling may have a potential role in walking rehabilitation, and future studies should examine the long-term effects on subclinical measures of reflex activity and its relationship to functional outcomes.

Law students show significant deficits in emotional and physical well-being compared with groups of students in other areas of higher education. Furthermore, evidence suggests that these effects may be worse for women than for men. The use of active coping can positively affect immunity under stress, but this may be most true for men in the context of law school. The current study examined the delayed-type hypersensitivity (DTH) skin responses of first-year law students (n=121) and a comparison group (n=30). Students' health behaviors, self-evaluative emotions, and coping strategies were also reported. Male law students had larger DTH responses than females, but this gender effect was not present in the comparison group. Endorsement of perseverance under stress (n=19), an active coping strategy, moderated the gender effect on immunity. Perseverance associated with larger DTH responses and more positive self-evaluative emotion, but only among men. These results indicate that active coping may be less efficacious for women than for men in law school, which in turn may limit women's opportunities to attenuate negative effects of law school.

This article summarizes the recent accomplishments and current challenges facing game-based virtual reality (VR) telerehabilitation. Specifically this article addresses accomplishments relative to realistic practice scenarios, part to whole practice, objective measurement of performance and progress, motivation, low cost, interaction devices and game design. Furthermore, a description of the current challenges facing game based telerehabilitation including the packaging, internet capabilities and access, data management, technical support, privacy protection, seizures, distance trials, scientific scrutiny and support from insurance companies.

Phylogeographic genomics, based on multiple complete mtDNA genome sequences from within individual vertebrate species, provides highly-resolved intraspecific trees for the detailed study of evolutionary biology. We describe new biogeographic and historical insights from our studies of the genomes of codfish, wolffish, and harp seal populations in the Northwest Atlantic, and from the descendants of the founding human population of Newfoundland. Population genomics by conventional sequencing methods remains laborious. A new biotechnology, iterative DNA "re-sequencing", uses a DNA microarray to recover 30-300 kb of contiguous DNA sequence in a single experiment. Experiments with a single-species mtDNA microarray show that the method is accurate and efficient, and sufficiently species-specific to discriminate mtDNA genomes of moderately-divergent taxa. Experiments with a multi-species DNA microarray (the "ArkChip") show that simultaneous sequencing of species in different orders and classes detects SNPs within each taxon with equal accuracy as single-species-specific experiments. Iterative DNA sequencing offers a practical method for high-throughput biodiversity genomics that will enable standardized, coordinated investigation of multiple species of interest to Species at Risk and conservation biologists.

Objective: To describe the sociodemographic, clinical, and forensic characteristics of people convicted of killing infants, including their outcome in court and the gender differences in these characteristics., Method: A consecutive case series of people convicted of infant homicide in England and Wales (1996-2001). Information on social demographic and clinical characteristics of perpetrators was collected from psychiatric reports prepared for court. Detailed clinical information was gathered from questionnaires completed by mental health teams for those in contact with mental health services., Results: Of the 2660 identified perpetrators that were convicted of homicide, 112 (4%) were convicted of infant homicide. Fathers killed 56 infants (50%); mothers killed 35 (31%). Forty-nine infants (44%) were killed within 3 months of birth, and 87 (78%) within 6 months. Seventeen perpetrators (24%) had symptoms of mental illness at the time of the offense. Thirty-eight (34%) had a lifetime history of mental illness. In total, 16 (14%) had been under the care of mental health services. Ten women (29%) were diagnosed with affective disorder, and 25 men (53%) had a history of alcohol or drug misuse. Men were more likely to have previous convictions for violence compared to women (p = .01). Most male perpetrators received a custodial sentence (N = 71, 96%), whereas 28 women (74%) received community sentences or hospital disposals., Conclusions: This study highlights the need for increased perinatal assessment and parenting support to encourage parents to seek help. Further research using a psychological autopsy methodology focusing on criminological and psychiatric antecedents may improve our understanding of why these deaths occur and prevent future tragedies.

Background: Iterative DNA "resequencing" on oligonucleotide microarrays offers a high-throughput method to measure intraspecific iodiversity, one that is especially suited to SNP-dense gene regions such as vertebrate mitochondrial (mtDNA) genomes. However, costs of single-species design and microarray fabrication are prohibitive. A cost-effective, multi-species strategy is to hybridize experimental DNAs from diverse species to a common microarray that is tiled with oligonucleotide sets from multiple, homologous reference genomes. Such a strategy requires that cross-hybridization between the experimental DNAs and reference oligos from the different species not interfere with the accurate recovery of species-specific data. To determine the pattern and limits of such interspecific hybridization, we compared the efficiency of sequence recovery and accuracy of SNP identification by a 15,452-base human-specific microarray challenged with human, chimpanzee, gorilla, and codfish mtDNA genomes., Results: In the human genome, 99.67% of the sequence was recovered with 100.0% accuracy. Accuracy of SNP identification declines log-linearly with sequence divergence from the reference, from 0.067 to 0.247 errors per SNP in the chimpanzee and gorilla genomes, respectively. Efficiency of sequence recovery declines with the increase of the number of interspecific SNPs in the 25b interval tiled by the reference oligonucleotides. In the gorilla genome, which differs from the human reference by 10%, and in which 46% of these 25b regions contain 3 or more SNP differences from the reference, only 88% of the sequence is recoverable. In the codfish genome, which differs from the reference by > 30%, less than 4% of the sequence is recoverable, in short islands > or = 12b that are conserved between primates and fish., Conclusion: Experimental DNAs bind inefficiently to homologous reference oligonucleotide sets on a re-sequencing microarray when their sequences differ by more than a few percent. The data suggest that interspecific cross-hybridization will not interfere with the accurate recovery of species-specific data from multispecies microarrays, provided that the species' DNA sequences differ by > 20% (mean of 5b differences per 25b oligo). Recovery of DNA sequence data from multiple, distantly-related species on a single multiplex gene chip should be a practical, highly-parallel method for investigating genomic biodiversity.

Objective: To evaluate the effectiveness and validity of the Functional Reach Test (FRT) as a screening tool to identify fallers (persons at risk for falls) among subjects with Parkinson's disease (PD) and control subjects., Design: A case-comparison design with a consecutive sample. Subjects performed 3 consecutive functional reach trials., Setting: Motor behavior laboratory in a university setting., Participants: Fifty-eight adults (43 subjects with PD, 15 control subjects). Controls were recruited from a Florida hospital and the local community., Interventions: Not applicable., Main Outcome Measures: A falls history was recorded, a mean FRT score attained, and FRT scores were categorized as less than 25.4 cm, the criterion for falls risk, or > or =25.4 cm., Results: Mean FRT scores differentiated subjects with PD and a known history of falls from subjects with PD and no history of falls and from control subjects (P <.001). Tests of validity for the FRT as a screening tool indicated sensitivity as 30%, specificity as 92%, positive predictive value as 90%, and negative predictive value as 36%., Conclusions: The FRT, using a reach less than 25.4 cm as a criterion for falls risk, is not a sensitive instrument for identifying individuals with PD at risk. However, the percentage of those persons identified as at risk by the FRT are highly likely at risk, and they should be referred for falls risk intervention. Because the FRT does not identify every person at risk, using a test battery addressing other factors contributing to falls risk may increase the sensitivity of a clinician's assessment to identify persons with PD at risk for falls., (Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation)

Objective: The purpose of this study was to assess the effect of a single bout of a locomotor-training paradigm on overground walking speed and H-reflex modulation of individuals with incomplete spinal cord injury (SCI)., Methods: Self-selected and maximum walking speeds and soleus H-reflexes (H/M ratios) during standing and stance and swing phases of walking (self-selected velocity) were obtained from 4 individuals with American Spinal Injury Association impairment classification D. Data were collected immediately before and after a single bout of locomotor training with body weight support on a treadmill. The pretraining H/M ratios of the SCI subjects were also compared with values from 4 able-bodied subjects who did not receive the intervention. Maximum H/M ratios while standing and during midstance and midswing phases of overground walking were considerably greater in the SCI subjects than in the control subjects., Results: After the single bout of training, self-selected and maximum overground walking speeds of the subjects with SCI increased by 26% and 25%, respectively. Furthermore, H-reflexes were significantly more depressed in the SCI subjects during overground walking (28% less during stance, 34% less during swing)., Conclusions: Although preliminary, these findings indicate that a single bout of locomotor training produced immediate increases in walking velocity and acute neurophysiologic changes in individuals with incomplete SCI.

The delivery of oligonucleotides to appropriate intracellular compartments is crucial to their development as tools in gene function studies and as therapeutics. Here, we report the characterization of meso-substituted cationic porphyrins as a large class of water-soluble reagents for oligonucleotide delivery. These porphyrins form non-covalent complexes with single-stranded oligonucleotides and deliver these molecules into the nuclei of cell lines in culture. The porphyrins protect oligonucleotides from nuclease degradation, and delivery is unaffected by the presence of serum. Delivery capacity is dependent on the charge ratio and concentration of the oligonucleotide and porphyrin used to form the complex, on the chemical substituents of the oligonucleotide and on the identity of the cationic porphyrin. This class of molecules provides a versatile set of water-soluble delivery reagents that could contribute to the development of oligonucleotide drugs.

The receptor-ligand interaction between hepatocyte heme receptors and heme was evaluated as a basis for developing a targeted cationic lipid delivery reagent for nucleic acids. Heme (ferric protoporphyrin IX) was conjugated to the aminolipid dioleoyl phosphatidylethanolamine (DOPE) and used to form cationic lipid particles with dioleoyl trimethylammonium propane (DOTAP). These lipids particles (DDH) protect oligoribonucleotides from degradation in human serum and increase oligoribonucleotide uptake into 2.2.15 human hepatoma cells (to a level of 50-60 ng oligo/10(4) cells) when compared with the same lipid particles (DD) prepared identically without heme. The DDH heme level that was optimal for oligoribonucleotide delivery was also optimal for maximum expression of plasmid-encoded luciferase. The enhancing effect of heme was evident only at net particle negative charge. Fluorescence microscopy showed that DDH delivered oligoribonucleotides into both the 2.2.15 cell cytoplasm and nucleus. DDH may thus be a potentially useful delivery vehicle for oligonucleotide-based therapeutics and transgenes, appropriate for use in such liver diseases as viral hepatitis, hepatoma, and hypercholesterolemia.

Effective stability constants for cysteine and lysine with five different iron sources were evaluated along with their behavior in solution. The values obtained for ferric chloride-cysteine, ferrous sulfate-cysteine, ferric chloride-lysine, ferrous sulfate-lysine, hydrogen-reduced lysine, and electrolytic-reduced lysine were 6.81 × 10 2 to 2.78 × 10 3 , 1.33 × 10 5 to 1.36 × 10 5 , 6.00 × 10 -4 to 7.64 × 10 -3 , 6.37 ×10 -4 to 4.82× 10 -3 , 9.34 × 10 -2 to 1.38 × 10 -1 , and 4.18 × 10 -4 to 7.27 × 10 -4 , respectively. No measurable complexation occurred with hydrogen- and electrolytic-reduced iron with cysteine nor with ferric orthophosphate and cysteine or lysine. The stability of soluble ferric cysteine over the pH range 2.0 to 7.4 indicates that this complex has the potential to be used as an iron additive in food. Approximately half of the hydrogen and electrolytic reduced iron and only 0.11% of ferric orthophosphate were soluble in acid, whereas ferric chloride and ferrous sulfate were completely soluble. Qualitative evaluation of the iron-amino acid systems over a range of pH from 2.0 to 12.0 indicated that there was a mixed valence state of free iron in most cases with low pH favoring reduction and high pH oxidation, until precipitation of iron hydroxides occurred.