Catalytic Activity and Electrochemical Stability of Ru1-xMxO2 (M = Zr, Nb, Ta): Computational and Experimental Study of the Oxygen Evolution Reaction.

We use computations and experiments to determine the effect of substituting zirconium, niobium, and tantalum within rutile RuO2 on the structure, oxygen evolution reaction (OER) mechanism and activity, and electrochemical stability. Calculated electronic structures altered by Zr, Nb, and Ta show surface regions of electron density depletion and accumulation, along with anisotropic lattice parameter shifts dependent on the substitution site, substituent, and concentration. Consistent with theory, X-ray photoelectron spectroscopy experiments show shifts in binding energies of O-2s, O-2p, and Ru-4d peaks due to the substituents. Experimentally, the substituted materials showed the presence of two phases with a majority phase that contains the metal substituent within the rutile phase and a second, smaller-percentage RuO2 phase. Our experimental analysis of OER activity shows Zr, Nb, and Ta substituents at 12.5 atom % induce lower activity relative to RuO2, which agrees with computing the average of all sites; however, Zr and Ta substitution at specific sites yields higher theoretical OER activity than RuO2, with Zr substitution suggesting an alternative OER mechanism. Metal dissolution predictions show the involvement of cooperative interactions among multiple surface sites and the electrolyte. Zr substitution at specific sites increases activation barriers for Ru dissolution, however, with Zr surface dissolution rates comparable to those of Ru. Experimental OER stability analysis shows lower Ru dissolution from synthesized RuO2 and Zr-substituted RuO2 compared to commercial RuO2 and comparable amounts of Zr and Ru dissolved from Zr-substituted RuO2, aligned with our calculations.

Conventional Fossil Fuel Extraction, Associated Biogeochemical Processes, and Topography Influence Methane Groundwater Concentrations in Appalachia.

The production of fossil fuels, including oil, gas, and coal, retains a dominant share in US energy production and serves as a major anthropogenic source of methane, a greenhouse gas with a high warming potential. In addition to directly emitting methane into the air, fossil fuel production can release methane into groundwater, and that methane may eventually reach the atmosphere. In this study, we collected 311 water samples from an unconventional oil and gas (UOG) production region in Pennsylvania and an oil and gas (O&G) and coal production region across Ohio and West Virginia. Methane concentration was negatively correlated to distance to the nearest O&G well in the second region, but such a correlation was shown to be driven by topography as a confounding variable. Furthermore, sulfate concentration was negatively correlated with methane concentration and with distance to coal mining in the second region, and these correlations were robust even when considering topography. We hypothesized that coal mining enriched sulfate in groundwater, which in turn inhibited methanogenesis and enhanced microbial methane oxidation. Thus, this study highlights the complex interplay of multiple factors in shaping groundwater methane concentrations, including biogeochemical conversion, topography, and conventional fossil extraction.

Birth plans: definitions, content, effects, and best practices.

The first written guide for birth plans was introduced in 1980 as a means for birthing people to document their choices in the child birthing experience. The birth plan offers an opportunity for the patient and the provider to discuss the birthing process and determine how to safely accommodate patient preferences. Patient satisfaction with birthing plans is variable and may depend on how many requests they have, how many of their plans are accomplished, route of delivery, and whether complications arise during or after delivery. Unmet expectations may lead to posttraumatic stress disorder, but following a birth plan may also be protective against it. Birthing people who use a birth plan may be less likely to use epidural anesthesia, have early amniotomy, or use oxytocin. The first stage of labor may be longer when a birth plan is used; however, there does not seem to be a decrease in the length of the second stage of labor among patients with a birth plan. Some providers believe that a disadvantage of birth plans is disappointment when birth plans are not able to be followed, and others consider that birth plans interfere with professional autonomy.

A Comprehensive Approach to Care of Women of Advanced Maternal Age.

Advanced maternal age, historically defined as ages 35 years and older, is used to describe the later years in the female reproductive life span when rates of adverse pregnancy outcomes increase. The preconception period represents an opportunity to ensure the use of safe medications and optimize care for medical comorbidities. Routine prenatal care should be augmented with counseling on fetal aneuploidy with a detailed anatomic survey. Surveillance for preterm labor and preeclampsia is recommended. Growth assessment and antepartum testing for specific women are advised, particularly those ages 40 years and older and those with select medical problems. Despite an increased incidence of complications, most women of advanced maternal age will have normal pregnancies and will benefit from the compassionate care provided by midwives, advanced practice registered nurses (including nurse practitioners and clinical nurse specialists), and perinatal nurses.

Same-Day Counseling: Study Protocol for the Evaluation of a New Mental Health Service.

BACKGROUND: Single-session counseling is being implemented across Canada to increase the accessibility and availability of mental health services. Despite increasing use, existing research on single-session counseling is sparse and has methodological limitations. In addition, some stakeholders are skeptical that this model of care can support meaningful change for clients. OBJECTIVE: The aim of this study is to evaluate a new single-session counseling program (called Same-Day Counseling) offered in an outpatient community mental health clinic in Northwestern Ontario, Canada. METHODS: Clients who attend Same-Day Counseling services will be given the opportunity to participate in the program evaluation. Those who consent will complete measures before their session, after their session, and at 1-month follow-up. Data will provide information on who accesses Same-Day Counseling (eg, typical presenting problems, symptom severity), client satisfaction with services, and whether clients benefit from the services (eg, improved functioning and reduced symptom severity). RESULTS: Data collection is underway with 80 participants having completed baseline measures and 55 participants having completed follow-up measures. Data collection is expected to conclude in December 2015. CONCLUSIONS: This study is designed to contribute to the literature regarding the integration of single-session counseling into ongoing mental health services, with additional attention to methodological rigour. Our approach will help to address ongoing concerns regarding the implementation of single-session counseling, and inform health care providers and policy makers regarding the utility of this model for addressing the mental health care need of the community.

Feasibility and potential efficacy of the family-centered Prevent-Teach-Reinforce model with families of children with developmental disorders.

This study examined the feasibility and potential efficacy of the family-centered Prevent-Teach-Reinforce (PTR) model with three families of young children with an autism spectrum disorder or language delay with sensory processing problems. Particularly, the study assessed the family adherence to the PTR intervention, changes in child behavior, family use of the Individualized Behavior Rating Scale Tool (IBRST), procedural integrity, and social validity. A multiple-baseline design across families was used to examine the functional relation between parent-implemented PTR intervention and changes in child behavior. Results indicated that the family-centered PTR process was successful in promoting parents to design and implement the PTR intervention plans with fidelity, and the parents' implemented intervention plans were effective in increasing replacement behavior and decreasing problem behavior across children. The results also indicated that the parents successfully used the IBRST to monitor their child's progress and were highly satisfied with the PTR intervention process and outcomes for their children.

Evidence of non-pancreatic beta cell-dependent roles of Tcf7l2 in the regulation of glucose metabolism in mice.

Non-coding variation within TCF7L2 remains the strongest genetic determinant of type 2 diabetes risk in humans. A considerable effort has been placed in understanding the functional roles of TCF7L2 in pancreatic beta cells, despite evidence of TCF7L2 expression in various peripheral tissues important in glucose homeostasis. Here, we use a humanized mouse model overexpressing Tcf7l2, resulting in glucose intolerance, to infer the contribution of Tcf7l2 overexpression in beta cells and in other tissues to the metabolic phenotypes displayed by these mice. Restoring Tcf7l2 expression specifically in beta cells to endogenous levels, in face of its overexpression elsewhere, results in impaired insulin secretion, reduced beta cell number and islet area, corroborating data obtained in humans showing similar phenotypes as a result of manipulations leading to Tcf7l2 loss of function. Interestingly, the persistent overexpression of Tcf7l2 in non-pancreatic tissues results in a significant worsening in glucose tolerance in vivo, indicating that Tcf7l2 overexpression in beta cells does not account for the glucose intolerance in the Tcf7l2 overexpression mouse model. Collectively, these data posit that Tcf7l2 plays key roles in glucose metabolism through actions beyond pancreatic beta cells, and further points to functionally opposing cell-type specific effects for Tcf7l2 on the maintenance of balanced glucose metabolism, thereby urging a careful examination of its role in non-pancreatic tissues as well as its composite metabolic effects across distinct tissues. Uncovering these roles may lead to new therapeutic targets for type 2 diabetes.

TCF7L2 is a master regulator of insulin production and processing.

Genome-wide association studies have revealed >60 loci associated with type 2 diabetes (T2D), but the underlying causal variants and functional mechanisms remain largely elusive. Although variants in TCF7L2 confer the strongest risk of T2D among common variants by presumed effects on islet function, the molecular mechanisms are not yet well understood. Using RNA-sequencing, we have identified a TCF7L2-regulated transcriptional network responsible for its effect on insulin secretion in rodent and human pancreatic islets. ISL1 is a primary target of TCF7L2 and regulates proinsulin production and processing via MAFA, PDX1, NKX6.1, PCSK1, PCSK2 and SLC30A8, thereby providing evidence for a coordinated regulation of insulin production and processing. The risk T-allele of rs7903146 was associated with increased TCF7L2 expression, and decreased insulin content and secretion. Using gene expression profiles of 66 human pancreatic islets donors', we also show that the identified TCF7L2-ISL1 transcriptional network is regulated in a genotype-dependent manner. Taken together, these results demonstrate that not only synthesis of proinsulin is regulated by TCF7L2 but also processing and possibly clearance of proinsulin and insulin. These multiple targets in key pathways may explain why TCF7L2 has emerged as the gene showing one of the strongest associations with T2D.

FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA.

N(6)-methyladenosine is a prevalent internal modification in messenger RNA and non-coding RNA affecting various cellular pathways. Here we report the discovery of two additional modifications, N(6)-hydroxymethyladenosine (hm(6)A) and N(6)-formyladenosine (f(6)A), in mammalian messenger RNA. We show that Fe(II)- and α-ketoglutarate-dependent fat mass and obesity-associated (FTO) protein oxidize N(6)-methyladenosine to generate N(6)-hydroxymethyladenosine as an intermediate modification, and N(6)-formyladenosine as a further oxidized product. N(6)-hydroxymethyladenosine and N(6)-formyladenosine have half-life times of ~3 h in aqueous solution under physiological relevant conditions, and are present in isolated messenger RNA from human cells as well as mouse tissues. These previously unknown modifications derived from the prevalent N(6)-methyladenosine in messenger RNA, formed through oxidative RNA demethylation, may dynamically modulate RNA-protein interactions to affect gene expression regulation.

Psychosocial assessment of nursing home residents via MDS 3.0: recommendations for social service training, staffing, and roles in interdisciplinary care.

The Minimum Data Set 3.0 has introduced a higher set of expectations for assessment of residents' psychosocial needs, including new interviewing requirements, new measures of depression and resident choice, and new discharge screening procedures. Social service staff are primary providers of psychosocial assessment and care in nursing homes; yet, research demonstrates that many do not possess the minimum qualifications, as specified in federal regulations, to effectively provide these services given the clinical complexity of this client population. Likewise, social service caseloads generally exceed manageable levels. This article addresses the need for enhanced training and support of social service and interdisciplinary staff in long term care facilities in light of the new Minimum Data Set 3.0 assessment procedures as well as new survey and certification guidelines emphasizing quality of life. A set of recommendations will be made with regard to training, appropriate role functions within the context of interdisciplinary care, and needs for more realistic staffing ratios.

Recognizing the importance of aging skills and knowledge in generalist social work practice: effective strategies for MSW students.

This article examines the impact of a curricular infusion strategy aimed at integrating gerontological practice issues into social work education. Findings (N = 83) illustrate that student interest, knowledge, and skills in aging practice increased immediately following implementation of a three-tiered infusion approach; however, ongoing exposure to gerontology in and out of the classroom appears necessary to sustain students' interest in working with older adults over time. Although the majority of students endorsed aging issues as important to social work in general, many did not understand its relevance to their own careers. Next steps are outlined to enable students to make this important connection.

Learning and memory impairments in a congenic C57BL/6 strain of mice that lacks the M2 muscarinic acetylcholine receptor subtype.

The neurotransmitter acetylcholine is an important modulator of cognitive functions including attention, learning, and memory. The actions of acetylcholine are mediated by five distinct muscarinic acetylcholine receptor subtypes (M(1)-M(5)). The lack of drugs with a high degree of selectivity for these subtypes has impeded the determination of which subtypes mediate which components of cholinergic neurotransmission relevant to cognitive abilities. The present study examined the behavioral functions of the M(2) muscarinic receptor subtype by utilizing congenic C57BL/6 mice possessing a null-mutation in the M(2) muscarinic receptor gene (M(2)(-/-) mice). Comprehensive assessment of general health and the neurological function found no major differences between M(2)(-/-) and wild-type (M(2)(+/+)) mice. In the tests of learning and memory, M(2)(-/-) mice were impaired in the acquisition (trials to criterion), but not the retention (72h) of a passive avoidance task. In a novel open field, M(2)(-/-) mice were impaired in between-sessions, but not within-session habituation. In a holeboard test of spatial memory, M(2)(-/-) mice committed more errors in working memory than M(2)(+/+) mice. Reference memory did not differ between the genotypes. M(2)(-/-) mice showed no impairments in either cued or contextual fear conditioning. These findings replicate and extend earlier findings in a hybrid strain and solidify the interpretation that the M(2) receptor plays a critical role in specific components of cognitive abilities.

Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function.

Loss-of-function mutations in the DJ-1 gene account for an autosomal recessive form of Parkinson's disease (PD). To investigate the physiological functions of DJ-1 in vivo, we generated DJ-1 knockout (DJ-1(-/-)) mice. Younger (<1 year) DJ-1(-/-) mice were hypoactive and had mild gait abnormalities. Older DJ-1(-/-), however, showed decreased body weight and grip strength and more severe gait irregularities compared to wild-type littermates. The basal level of extracellular dopamine, evoked dopamine release and dopamine receptor D2 sensitivity appeared normal in the striatum of DJ-1(-/-) mice, which was consistent with similar results between DJ-1(-/-) and controls in behavioral paradigms specific for the dopaminergic system. An examination of spinal cord, nerve and muscle tissues failed to identify any pathological changes that were consistent with the noted motor deficits. Taken together, our findings suggest that loss of DJ-1 leads to progressive behavioral changes without significant alterations in nigrostriatal dopaminergic and spinal motor systems.

Effects of frontal cortex lesions on action sequence learning in the rat.

To understand the role of frontal cortex in motor sequence learning we compared the effects of motor (M1), premotor (M2) and midline frontal (MFr) cortical lesions on rats making nose-pokes guided by luminance cues. Organizational demands were manipulated by varying the number (1 vs. 5) and predictability (random vs. repeated) of nose-pokes in a response. Learning was studied by comparing sessions with random or repeated cues. All cortical lesions increased reaction time (RT) during response initiation. These effects were larger for nose-pokes initiating sequential responses but spared RT for nose-pokes completing them. Repetition learning had significant effects on the speed and accuracy of single nose-poke responses that were unaffected by any of the cortical lesions. Repetition learning had more complex effects on sequential responding. RTs increased for nose-pokes initiating sequences over several sessions of continuous repetition and then decreased or leveled off. RTs decreased incrementally across all repetition sessions for subsequent nose-pokes in repeated sequences, following a time-course consistent with habit learning. Lesions involving M2 and MFr cortex exacerbated the increase in RT during initiation without affecting the incremental decrease in RT for nose-pokes completing repeated sequences. These results were confirmed by analyses of interference effects when training shifted from repeated (learned) to random (novel) sequences or to a new repeated sequence. These results implicate dorsomedial frontal cortex in organizational aspects of sensory-guided responding and motor sequence learning reflected in RT during response initiation.

Galanin receptor subtype 2 (GalR2) null mutant mice display an anxiogenic-like phenotype specific to the elevated plus-maze.

The neuropeptide galanin has been implicated in anxiety-related behaviors, cognition, analgesia, and feeding in rodents. Neuromodulatory actions of galanin are mediated by three G-protein coupled receptors, GalR1, GalR2, and GalR3. The present study investigates the role of the GalR2 receptor by evaluating behavioral phenotypes of mice with a targeted mutation in the GalR2 gene. A three-tiered behavioral phenotyping approach first examined control measures of general health, body weight, neurological reflexes, sensory abilities and motor function. Mice were then assessed on several tests for cognitive and anxiety-like behaviors. GalR2 null mutants and heterozygotes were not significantly different from wildtype littermates on two cognitive tests previously shown to be sensitive to galanin manipulation: acquisition of the Morris water maze spatial task, and trace cued and contextual fear conditioning, an emotional learning and memory task. Two independent cohorts of GalR2 null mutant mice demonstrated an anxiogenic-like phenotype in the elevated plus-maze. No genotype differences were detected on several other measures of anxiety-like behavior. The discovery of an anxiogenic phenotype specific to the elevated plus-maze, similar to findings in GalR1 null mutants, highlights the potential therapeutic efficacy of targeting GalR1 and GalR2 receptors in treating anxiety disorders.

Behavioral phenotyping of transgenic and knockout mice: practical concerns and potential pitfalls.

New technologies in molecular genetics have dramatically increased the number of targeted gene mutations available to the biomedical research community. Many mutant mouse lines have been generated to provide animal models for human genetic disorders, offering insights into anatomical, neurochemical, and behavioral effects of aberrant gene expression. A variety of assays have been developed to identify and characterize phenotypic changes. In the behavioral domain, our phenotyping strategy involves a comprehensive standardized methodological approach that assesses general health, reflexes, sensory abilities, and motor functions. This assessment is followed by a series of complementary tasks in the specific behavioral domain(s) hypothesized to reveal the function(s) of the gene. Our multitiered approach minimizes intersubject variability by standardizing the experimental history for all animals, improves interlaboratory reliability by providing a clearly defined experimental protocol, and minimizes artifactual interpretations of behavioral data by careful preliminary assessments of basic behaviors, followed by multiple tests within the behavioral domain of interest. Despite meticulous attention to experimental protocol, attention to environmental factors is essential. Differences in noise, light, home cage environment, handling, and diet can dramatically alter behavior. Baseline differences in the behaviors of inbred strains used to generate targeted mutant mouse lines can directly influence the behavioral phenotype of the mutant line. Strategies aimed at minimizing environmental variability and contributions of background genes will enhance the robustness of mouse behavioral phenotyping assays.

The role of striatum in initiation and execution of learned action sequences in rats.

To understand the role of striatum in motor sequence learning, we trained rats to perform a series of tasks measuring speed and accuracy of responding to luminance cues presented as discriminative stimuli for single nose pokes or for sequences of nose pokes in a serial reaction time task. Habit (stimulus-response) learning was measured by comparing performances when stimuli were repeated (predictable) with when they were selected randomly (unpredictable). Sequences had defined start and end points and were limited to five nose pokes to minimize chunking. When sequences were repeated, response time (RT) increased for nose pokes initiating the sequence and decreased for nose pokes completing it. These effects developed incrementally across sessions, consistent with the time course of habit learning. Medial (mCPu), lateral, and complete (CPu) caudate-putamen lesions affected speed and accuracy of single nose poke responses, confirming the role of these areas in guiding responses with external sensory stimuli. None of these lesions affected the short-term increase in accuracy observed when single nose poke responses were repeated. Both mCPu and CPu lesions increased RTs for initiating sequential responses, effects that were exacerbated across sessions in which specific sequences were repeated. None of the lesions affected the gradual decrease in RT for nose pokes completing repeated sequences. Correlational analyses confirmed the relationship between the extent of dorsal striatal damage and the ability to respond to brief luminance cues and to initiate learned sequences. These results provide evidence implicating dorsal striatum in higher-level organizational aspects of learning reflected in planning that precedes the execution of learned action sequences.

Galanin impairs performance on learning and memory tasks: findings from galanin transgenic and GAL-R1 knockout mice.

Galanin (GAL) impairs performance on cognitive tasks when administered centrally to rats. GAL transgenic (GAL-tg) mice overexpressing endogenous GAL show deficits on the probe trial of the Morris water maze spatial learning task, on the social transmission of food preference olfactory memory task, and on the trace cued fear conditioning emotional learning and memory task. Knockout mice deficient in the GAL-R1 receptor subtype were normal on most memory tasks, while showing a small deficit in trace cued fear conditioning, suggesting a selective role for the GAL-R1 in aversive memories, and implicating other GAL receptor subtypes in spatial learning and olfactory social memory. The growing body of rodent literature implicating excess GAL in cognitive impairment is relevant to the overexpression of GAL in the basal forebrain during the progression of Alzheimer's disease.