Macrocyclic Oxindole Peptide Epoxyketones-A Comparative Study of Macrocyclic Inhibitors of the 20S Proteasome.

Peptide macrocycles have recently gained attention as protease inhibitors due to their metabolic stability and specificity. However, the development of peptide macrocycles with improved binding potency has so far been challenging. Here we present macrocyclic peptides derived from the clinically applied proteasome inhibitor carfilzomib with an oxindole group that mimics the natural product TMC-95A. Fluorescence kinetic activity assays reveal a high potency of the oxindole group (IC50 = 0.19 µM) compared with agents lacking this motif. X-ray structures of the ligands with the ß5-subunit of the yeast 20S proteasome illustrate that the installed macrocycle forces strong hydrogen bonding of the oxindole group with ß5-Gly23NH. Thus, the binding of our designed oxindole epoxyketones is entropically and enthalpically favored in contrast to more flexible proteasome inhibitors such as carfilzomib.

Upper and Lower Motor Neurons and the Skeletal Muscle: Implication for Amyotrophic Lateral Sclerosis (ALS).

The relationships between motor neurons and the skeletal muscle during development and in pathologic contexts are addressed in this Chapter.We discuss the developmental interplay of muscle and nervous tissue, through neurotrophins and the activation of differentiation and survival pathways. After a brief overview on muscular regulatory factors, we focus on the contribution of muscle to early and late neurodevelopment. Such a role seems especially intriguing in relation to the epigenetic shaping of developing motor neuron fate choices. In this context, emphasis is attributed to factors regulating energy metabolism, which may concomitantly act in muscle and neural cells, being involved in common pathways.We then review the main features of motor neuron diseases, addressing the cellular processes underlying clinical symptoms. The involvement of different muscle-associated neurotrophic factors for survival of lateral motor column neurons, innervating MyoD-dependent limb muscles, and of medial motor column neurons, innervating Myf5-dependent back musculature is discussed. Among the pathogenic mechanisms, we focus on oxidative stress, that represents a common and early trait in several neurodegenerative disorders. The role of organelles primarily involved in reactive oxygen species scavenging and, more generally, in energy metabolism-namely mitochondria and peroxisomes-is discussed in the frame of motor neuron degeneration.We finally address muscular involvement in amyotrophic lateral sclerosis (ALS), a multifactorial degenerative disorder, hallmarked by severe weight loss, caused by imbalanced lipid metabolism. Even though multiple mechanisms have been recognized to play a role in the disease, current literature generally assumes that the primum movens is neuronal degeneration and that muscle atrophy is only a consequence of such pathogenic event. However, several lines of evidence point to the muscle as primarily involved in the disease, mainly through its role in energy homeostasis. Data from different ALS mouse models strongly argue for an early mitochondrial dysfunction in muscle tissue, possibly leading to motor neuron disturbances. Detailed understanding of skeletal muscle contribution to ALS pathogenesis will likely lead to the identification of novel therapeutic strategies.

Exploring what progress is being made in the development of health promotion material for vascular dementia: A systematic review of the evidence.

A systematic review conducted by Price and Keady (Journal of Nursing and Healthcare of Chronic Illness, 2, 88 and 2010) demonstrated that there was a dearth of health-promoting literature available for people diagnosed with vascular dementia. The correlation between health behavior and the onset of cardiovascular change that can lead to vascular dementia had demonstrated a need for health education and health-promoting information to be made accessible to vulnerable populations to ameliorate the risk of cognitive decline because of cardiovascular disease. Dementia is a progressive and life-limiting condition and with limited treatment options and a lack of progress in identifying a way to delay onset or even cure the condition. Focus must be targeted towards risk reduction strategies that serve to reduce onset and decline and limit the global burden on not only the individual with the condition and their carers but also to the health and social care economy. To identify the progress that has been made in developing health-promoting literature and patient education guidance since 2010 a systematic literature review was undertaken. Using thematic analysis, CINAHL, MEDLINE, and psych INFO databases were accessed and following PRISMA guidelines an inclusion and exclusion criteria was developed in order to locate peer-reviewed articles. Titles and abstracts were reviewed to identify a match with key terms, and from 133 screened abstracts eight studies met the inclusion requirements. From the eight studies, thematic analysis was implemented to identify shared understanding of experiences relating to health promotion in vascular dementia. The methodology for the study was replicated from the authors' previous systematic review in 2010. Five key themes were identified in the literature (Healthy heart healthy brain; Risk factors; Risk reduction/modification; Interventions; Absence of targeted health promotion). From what little evidence was available to review the thematic analysis has demonstrated developments in knowledge into the link between the onset of cognitive impairment and vascular dementia because of compromised cardiovascular health. Modifying health behavior has become essential in ameliorating the risk of vascular cognitive decline. With these developments the synthesis of the literature demonstrates that even with these insights there continues to be a lack of targeted material that individuals can access to understand the link between cardiovascular health and cognitive decline. It is recognized that maximizing cardiovascular health has the potential to lessen the risk of vascular cognitive impairment and vascular dementia developing and progressing yet targeted health promoting material remains lacking. With the developments in understanding the causal links between poor cardiovascular health, vascular cognitive impairment, and vascular dementia progress now needs to be made in developing targeted health promotion material for individuals to access to share this knowledge to reduce the potential onset and subsequent burden of dementia.

Heat shock transcription factors demonstrate a distinct mode of interaction with mitotic chromosomes.

A large number of transcription factors have been shown to bind and interact with mitotic chromosomes, which may promote the efficient reactivation of transcriptional programs following cell division. Although the DNA-binding domain (DBD) contributes strongly to TF behavior, the mitotic behaviors of TFs from the same DBD family may vary. To define the mechanisms governing TF behavior during mitosis in mouse embryonic stem cells, we examined two related TFs: Heat Shock Factor 1 and 2 (HSF1 and HSF2). We found that HSF2 maintains site-specific binding genome-wide during mitosis, whereas HSF1 binding is somewhat decreased. Surprisingly, live-cell imaging shows that both factors appear excluded from mitotic chromosomes to the same degree, and are similarly more dynamic in mitosis than in interphase. Exclusion from mitotic DNA is not due to extrinsic factors like nuclear import and export mechanisms. Rather, we found that the HSF DBDs can coat mitotic chromosomes, and that HSF2 DBD is able to establish site-specific binding. These data further confirm that site-specific binding and chromosome coating are independent properties, and that for some TFs, mitotic behavior is largely determined by the non-DBD regions.

Mountaintop removal coal mining impacts on structural and functional indicators in Central Appalachian streams.

Mountaintop removal coal mining (MTR) has been a major source of landscape change in the Central Appalachians of the United States (US). Changes in stream hydrology, channel geomorphology and water quality caused by MTR coal mining can lead to severe impairment of stream ecological integrity. The objective of the Clean Water Act (CWA) is to restore and maintain the ecological integrity of the Nation's waters. Sensitive, readily measured indicators of ecosystem structure and function are needed for the assessment of stream ecological integrity. Most CWA assessments rely on structural indicators; inclusion of functional indicators could make these assessments more holistic and effective. The goals of this study were: (1) test the efficacy of selected carbon (C) and nitrogen (N) cycling and microbial structural and functional indicators for assessing MTR coal mining impacts on streams; (2) determine whether indicators respond to impacts in a predictable manner; and (3) determine if functional indicators are less likely to change than are structural indicators in response to stressors associated with MTR coal mining. The structural indicators are water quality and sediment organic matter concentrations, and the functional indicators relate to microbial activity and biofilm production. Seasonal measurements were conducted over the course of a year in streams draining small MTR-impacted and forested watersheds in the Twentymile Creek watershed of West Virginia (WV). Five of the eight structural parameters measured had significant responses, with all means greater in the MTR-impacted streams than in the forested streams. These responses resulted from changes in source or augmentation of the original source of the C and N structural parameters because of MTR coal mining. Nitrate concentration and the stable carbon isotopic ratio of dissolved inorganic carbon were the most effective indicators evaluated in this study. Only three of the fourteen functional indicators measured had significant responses to MTR coal mining, with all means greater in the forested streams than in the MTR-impacted streams. These results suggest that stressors associated with MTR coal mining caused reduction in some aspects of microbial cycling, but resource subsidies may have counterbalanced some of the inhibition leading to no observable change in most of the functional indicators. The detritus base, which is thought to confer functional stability, was likely sustained in the MTR-impacted streams by channel storage and/or leaf litter inputs from their largely intact riparian zones. Overall, our results largely support the hypothesis that certain functional processes are more resistant to stress induced change than structural properties but also suggest the difficulty of identifying suitable functional indicators for ecological integrity assessment.

HOTAIR beyond repression: In protein degradation, inflammation, DNA damage response, and cell signaling.

Long noncoding RNAs (lncRNAs) are pervasively transcribed from the mammalian genome as transcripts that are usually >200 nucleotides long. LncRNAs generally do not encode proteins but are involved in a variety of physiological processes, principally as epigenetic regulators. HOX transcript antisense intergenic RNA (HOTAIR) is a well-characterized lncRNA that has been implicated in several cancers and in various other diseases. HOTAIR is a repressor lncRNA and regulates various repressive chromatin modifications. However, recent studies have revealed additional functions of HOTAIR in regulation of protein degradation, microRNA (miRNA) sponging, NF-κB activation, inflammation, immune signaling, and DNA damage response. Herein, we have summarized the diverse functions and modes of action of HOTAIR in protein degradation, inflammation, DNA repair, and diseases, beyond its established functions in gene silencing.

Emerging Roles of Protease-Activated Receptors (PARs) in the Modulation of Synaptic Transmission and Plasticity.

Protease-activated receptors (PARs) are a class of G protein-coupled receptors (GPCRs) with a unique mechanism of activation, prompted by a proteolytic cleavage in their N-terminal domain that uncovers a tethered ligand, which binds and stimulates the same receptor. PARs subtypes (PAR1-4) have well-documented roles in coagulation, hemostasis, and inflammation, and have been deeply investigated for their function in cellular survival/degeneration, while their roles in the brain in physiological conditions remain less appreciated. Here, we describe PARs' effects in the modulation of neurotransmission and synaptic plasticity. Available evidence, mainly concerning PAR1-mediated and PAR2-mediated regulation of glutamatergic and GABAergic transmission, supports that PARs are important modulators of synaptic efficacy and plasticity in normal conditions.

Advances in visualizing transcription factor - DNA interactions.

At the heart of the transcription process is the specific interaction between transcription factors (TFs) and their target DNA sequences. Decades of molecular biology research have led to unprecedented insights into how TFs access the genome to regulate transcription. In the last 20 years, advances in microscopy have enabled scientists to add imaging as a powerful tool in probing two specific aspects of TF-DNA interactions: structure and dynamics. In this review, we examine how applications of diverse imaging technologies can provide structural and dynamic information that complements insights gained from molecular biology assays. As a case study, we discuss how applications of advanced imaging techniques have reshaped our understanding of TF behavior across the cell cycle, leading to a rethinking in the field of mitotic bookmarking.

Protease-activated receptor 1 (PAR1) inhibits synaptic NMDARs in mouse nigral dopaminergic neurons.

Protease-activated receptor 1 (PAR1) is a G protein-coupled receptor (GPCR), whose activation requires a proteolytic cleavage in the extracellular domain exposing a tethered ligand, which binds to the same receptor thus stimulating Gαq/11-, Gαi/o- and Gα12-13 proteins. PAR1, activated by serine proteases and matrix metalloproteases, plays multifaceted roles in neuroinflammation and neurodegeneration, in stroke, brain trauma, Alzheimer's diseases, and Parkinson's disease (PD). Substantia nigra pars compacta (SNpc) is among areas with highest PAR1 expression, but current evidence on its roles herein is restricted to mechanisms controlling dopaminergic (DAergic) neurons survival, with controversial data showing PAR1 either fostering or counteracting degeneration in PD models. Since PAR1 functions on SNpc DAergic neurons activity are unknown, we investigated if PAR1 affects glutamatergic transmission in this neuronal population. We analyzed PAR1's effects on NMDARs and AMPARs by patch-clamp recordings from DAergic neurons from mouse midbrain slices. Then, we explored subunit composition of PAR1-sensitive NMDARs, with selective antagonists, and mechanisms underlying PAR1-induced NMDARs modulation, by quantifying NMDARs surface expression. PAR1 activation inhibits synaptic NMDARs in SNpc DAergic neurons, without affecting AMPARs. PAR1-sensitive NMDARs contain GluN2B/GluN2D subunits. Moreover, PAR1-mediated NMDARs hypofunction is reliant on NMDARs internalization, as PAR1 stimulation increases NMDARs intracellular levels and pharmacological limitation of NMDARs endocytosis prevents PAR1-induced NMDARs inhibition. We reveal that PAR1 regulates glutamatergic transmission in midbrain DAergic cells. This might have implications in brain's DA-dependent functions and in neurological/psychiatric diseases linked to DAergic dysfunctions.

Adsorption Behavior of Organic Molecules: A Study of Benzotriazole on Cu(111) with Spectroscopic and Theoretical Methods.

The adsorption of organic molecules on solid substrates is important to applications in fields such as catalysis, photovoltaics, corrosion inhibition, adhesion, and sensors. The molecular level description of the surface-molecule interaction and of the adsorption structures in these complex systems is crucial to understand their properties and function. Here, we present an investigation of one such system, benzotriazole (BTAH) on single-crystal Cu(111) in vacuum conditions. BTAH is the most widely used corrosion inhibitor for copper and thus a molecule of great industrial relevance. We show that the co-application of a wide range of spectroscopic techniques with theoretical methods provides unique insight in the description of the atomistic details of the adsorbed structures. Specifically, spectroscopic photoemission, absorption, and standing wave experiments combined with ab initio computational modeling allowed us to identify that benzotriazole forms overlayers of intact BTAH when deposited at low temperature, and it dissociates into BTA and H at room temperature and above. The dissociated molecule then forms complex structures of mixed chains and dimers of BTA bound to copper adatoms. Our work also reveals that copper adatoms at low concentrations, such as the theoretically predicted superstructures, cannot be resolved by means of current X-ray photoelectron spectroscopy as the modeled Cu 2p spectra are practically indistinguishable from those for a Cu surface without adatoms. Overall this study significantly deepens understanding of BTAH on Cu, a system studied for more than 50 years, and it highlights the benefits of combining spectroscopic and computational methods to obtain a complete picture of a complex adsorption system.

The mechanism in junctional failure of thoraco-lumbar fusions. Part I: Biomechanical analysis of mechanisms responsible of vertebral overstress and description of the cervical inclination angle (CIA).

PURPOSE: The purpose of the study is to describe the biomechanical theory explaining junctional breakdowns in thoraco-lumbar fusions, by taking the example of vertebral compression fractures. Also, a new angle, the cervical inclination angle (CIA), describing the relative position of the head at each vertebral level, is presented. METHODS: For the CIA, the data were collected from 137 asymptomatic subjects of a prospective database, containing clinical and radiologic informations. All the 137 subjects have an Oswestry score less than 15% and a pain score less than 2/10 and were part of a previously published study describing the Odontoïd-hip axis angle (ODHA). For each vertebral level from T1 to T12, the CIA as well as the vertical and horizontal distances was measured in reference to the sella turcica (ST), and a vertical line drawn from the ST. Average values and correlation coefficients were calculated. RESULTS: The CIA is an angle whose average value varies very little between T1 and T5 (74.9°-76.85°), and then increases progressively from T6 to T12. T1-T5 vertebra are always in line within the thoracic spine for each subject and can be considered as a straight T1-T5 segment. In addition, it was found that the vertical inclination of T1-T5 segment is correlated with the C7 slope (R 2 = 0.6383). CONCLUSION: The T1-T5 segment inclination is correlated with the C7 slope, and because the latter defines the cervical curve as previously shown, the T1-T5 segment can be considered as the base from which the cervical spine originates. Its role is, thus, similar to the pelvis and its sacral slope, which is the base from which the lumbar spine originates. The CIA along with the ODHA, which describes the adequacy of the global balance in young and elderly asymptomatic populations, are two important parameters that could help us to better understand junctional breakdowns in thoraco-lumbar fusion surgeries.

The mechanism in junctional failure of thoraco-lumbar fusions. Part II: Analysis of a series of PJK after thoraco-lumbar fusion to determine parameters allowing to predict the risk of junctional breakdown.

PURPOSE: To identify risk factors, in 12 patients with junctional breakdown (JBD) after thoraco-sacral fusions and to test a software locating maximal bending moment on full spine EOS images. METHODS: Twelve patients underwent long fusions for lumbar degenerative pathologies. Preop EOS images were compared to first postop EOS showing JBD. Parameters analyzed were: spinopelvic parameters [pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), sagittal vertical axis (SVA), spinosacral angle (SSA), lordosis, and kyphosis], proximal junctional angle (PJA), odontoid-hip axis angle (ODHA), and CIA. A new software estimated the location of maximum bending moment (M max) before and after JBD. RESULTS: All patients except one had a JBD located between T10 and L1, diagnosed at average follow-up of 18.58 months. JBD was a fracture in six patients, severe adjacent disc degeneration in the remaining. Average PI was 52°. PT increased, SS decreased after JBD versus preop (p > 0.05). Average PJA was 34.5°. Global lordosis (GLL), upper lordosis (ULL), L4-S1 lordosis, and thoracic kyphosis (TK) were increased (p < 0.05). Lower lumbar lordosis (LLL), was not increased postJBD (p = 0.6). SVA, SSA, ODHA, and C7 slope were not modified (p > 0.05). CIA average value decreased by 7.5% after JBD. T1-T5 alignment was correlated to C7 slope before (R 2 = 0.77075) and after JBD (R 2 = 0.85409). ODHA decreased after JBD (p > 0.05). Most JBD occurred at or one level away from preoperative M max location. CONCLUSION: This study confirms the importance of harmonious distribution of lumbar (GLL, ULL, and ILL) and thoracic curves (TK, T1-T5 segment) in thoraco-sacral fusions. All patients showed an exaggerated ULL, resulting in a posterior shift and increased lever arm at the thoraco-lumbar junction, leading to JBD.

Team-Based Interprofessional Competency Training for Dementia Screening and Management.

As many as 50% of people satisfying diagnostic criteria for dementia are undiagnosed. A team-based training program for dementia screening and management was developed targeting four professions (medicine, nursing, pharmacy, social work) whose scope of practice involves dementia care. An interprofessional group of 10 faculty members was trained to facilitate four interactive competency stations on dementia screening, differential diagnoses, dementia management and team care planning, and screening for and managing caregiver stress. Registrants were organized into teams of five members, with at least one member of each profession per team. The teams rotated through all stations, completing assigned tasks through interprofessional collaboration. A total of 117 professionals (51 physicians, 11 nurses, 20 pharmacists, 24 social workers, 11 others) successfully completed the program. Change scores showed significant improvements in overall competence in dementia assessment and intervention (very low = 1; very high = 5; average change 1.12, P < .001), awareness of importance of dementia screening (average change 0.85, P < .001), and confidence in managing medication (average change 0.86, P < .001). Eighty-seven participants (82.9%) reported feeling confident or very confident using the dementia toolkit at their home institution. In a survey administered 3 months after the session, 48 respondents reported that they had changed their approach to administering the Mini-Cog test (78%), differential diagnosis (49%), assessment of caregiver stress (74%), and accessing community support and services (69%). In conclusion, team-based interprofessional competency training is a team teaching model that can be used to enhance competency in dementia screening and management in medical, nursing, pharmacy, and social work practitioners.

Effect of cytostatic proline rich polypeptide-1 on tumor suppressors of inflammation pathway signaling in chondrosarcoma.

Cytokines produced in the tumour microenvironment exert an important role in cancer pathogenesis and in the inhibition of disease progression. Cancer of the cartilage is termed metastatic chondrosarcoma; however, the signaling events resulting in mesenchymal cell transformation to sarcoma have yet to be fully elucidated. The present study aimed to characterize the cytokine expression profile in the human JJ012 chondrosarcoma cell line, as well as the effect of cytostatic proline-rich polypeptide-1 (PRP-1). Western blot experiments demonstrated that the levels of suppressor of cytokine signaling 3 (SOCS3) were upregulated in chondrocytes compared with chondrosarcoma cells. Addition of PRP-1 restored the expression of the tumor suppressors, SOCS3 and ten-eleven-translocation methylcytosine dioxygenase 1 and 2 (TET1/2), in a dose-responsive manner. It is known that methylation of histone H3K9 was eliminated from the promoters of the inflammation-associated genes. PRP-1 inhibited H3K9 demethylase activity with an IC50 (concentration required to give half-maximal inhibition) value of 3.72 µg/ml in the chondrosarcoma cell line. Data obtained from ELISA experiments indicated that the expression of interleukin-6 (IL-6) in chondrosarcoma cells was 86-fold lower compared with that in C28 chondrocytes. In the present study, a 53-fold downregulation of IL-6 expression in co-culture of chondrosarcoma cells and C28 chondrocytes was identified as well. Downregulation of IL-6 expression has been documented in numerous other tumor types, although the reasons for this have not been fully established. In chondrosarcoma, IL-6 manifests itself as an anti-inflammatory agent and, possibly, as an anti-tumorigenic factor. To explore protein-DNA interactions leading to such differences, a gel-shift chemiluminescent assay was performed. Gel shifts were observed for chondrosarcoma and chondrocytes in the lanes that contained nuclear cell extract and oligo-IL-6 DNA. Notably, the DNA-protein complexes in C28 chondrocytes were markedly larger compared with those in chondrosarcoma cells. The mechanisms that underpin such differences, and characterization of the interacting proteins, remain to be fully elucidated.

Further Manipulations in Response Effort or Magnitude of an Aversive Consequence to Increase Self-Feeding in Children with Feeding Disorders.

Although some children with feeding disorders may have the necessary skills to feed themselves, they may lack motivation to self-feed solids and liquids. Rivas, Piazza, Roane, Volkert, Stewart, Kadey, and Groff (Journal of Applied Behavior Analysis, 47, 1-14, 2014) and Vaz, Volkert, and Piazza (Journal of Applied Behavior Analysis, 44, 915-920, 2011) successfully increased self-feeding for children who lacked motivation to self-feed by manipulating either the quantity or the quantity and quality of bites that the therapist fed the child if he or she did not self-feed. In the current investigation, we present three case examples to illustrate some challenges we faced when using these procedures outlined in the aforementioned studies and how we addressed these challenges.

Erratum to: Further Manipulations in Response Effort or Magnitude of an Aversive Consequence to Increase Self-Feeding in Children with Feeding Disorders.

[This corrects the article DOI: 10.1007/s40617-016-0124-1.].

A Practice Improvement Education Program Using a Mentored Approach to Improve Nursing Facility Depression Care-Preliminary Data.

Depression is common in nursing facility residents. Depression data obtained using the Minimum Data Set (MDS) 3.0 offer opportunities for improving diagnostic accuracy and care quality. How best to integrate MDS 3.0 and other data into quality improvement (QI) activity is untested. The objective was to increase nursing home (NH) capability in using QI processes and to improve depression assessment and management through focused mentorship and team building. This was a 6-month intervention with five components: facilitated collection of MDS 3.0 nine-item Patient Health Questionnaire (PHQ-9) and medication data for diagnostic interpretation; education and modeling on QI approaches, team building, and nonpharmacological depression care; mentored team meetings; educational webinars; and technical assistance. PHQ-9 and medication data were collected at baseline and 6 and 9 months. Progress was measured using team participation measures, attitude and care process self-appraisal, mentor assessments, and resident depression outcomes. Five NHs established interprofessional teams that included nursing (44.1%), social work (20.6%), physicians (8.8%), and other disciplines (26.5%). Members participated in 61% of eight offered educational meetings (three onsite mentored team meetings and five webinars). Competency self-ratings improved on four depression care measures (P = .05 to <.001). Mentors observed improvement in team process and enthusiasm during team meetings. For 336 residents with PHQ-9 and medication data, depression scores did not change while medication use declined, from 37.2% of residents at baseline to 31.0% at 9 months (P < .001). This structured mentoring program improved care processes, achieved medication reductions, and was well received. Application to other NH-prevalent syndromes is possible.

Preparing the workforce for healthy aging programs: the Skills for Healthy Aging Resources and Programs (SHARP) model.

Current public health and aging service agency personnel have little training in gerontology, and virtually no training in evidence-based health promotion and disease management programs for older adults. These programs are rapidly becoming the future of our community-based long-term care support system. The purpose of this project was to develop and test a model community college career technical education program, Skills for Healthy Aging Resources and Programs (SHARP), for undergraduate college students, current personnel in aging service and community organizations, and others interested in retraining. A multidisciplinary cross-sector team from disciplines of public health, sociology, gerontology and nursing developed four competency-based courses that focus on healthy aging, behavior change strategies, program management, an internship, and an option for leader training in the Chronic Disease Self-Management Program. To enhance implementation and fidelity, intensive faculty development training was provided to all instructors and community agency partners. Baseline and postprogram evaluation of competencies for faculty and students was conducted. Process evaluation for both groups focused on satisfaction with the curricula and suggestions for program improvement. SHARP has been piloted five times at two community colleges. Trainees (n = 113) were primarily community college students (n = 108) and current aging service personnel (n = 5). Statistically significant improvements in all competencies were found for both faculty and students. Process evaluation outcomes identified the needed logical and component adaptations to enhance the feasibility of program implementation, dissemination, and student satisfaction. The SHARP program provides a well-tested, evidence-based effective model for addressing workforce preparation in support of healthy aging service program expansion and delivery.

The Israel Diabetes and Cognitive Decline (IDCD) study: Design and baseline characteristics.

BACKGROUND: Type 2 diabetes (T2D) is associated with increased risk of dementia. The prospective longitudinal Israel Diabetes and Cognitive Decline study aims at identifying T2D-related characteristics associated with cognitive decline. METHODS: Subjects are population-based T2D 65+, initially cognitively intact. Medical conditions, blood examinations, and medication use data are since 1998; cognitive, functional, demographic, psychiatric, DNA, and inflammatory marker study assessments were conducted every 18 months. Because the duration of T2D reflects its chronicity and implications, we compared short (0-4.99 years), moderate (5-9.99), and long (10+) duration for the first 897 subjects. RESULTS: The long duration group used more T2D medications, had higher glucose, lower glomerular filtration rate, slower walking speed, and poorer cognitive functioning. Duration was not associated with most medical, blood, urine, and vital characteristics. CONCLUSIONS: Tracking cognition, with face-to-face evaluations, exploiting 15 years of historical detailed computerized, easily accessible, and validated T2D-related characteristics may provide novel insights into T2D-related dementia.

The interactive effects of PTSD, emotion regulation, and anger management strategies on female-perpetrated IPV.

Research supports a relationship between posttraumatic stress disorder (PTSD) symptoms and intimate partner violence (IPV) perpetration, and theory implicates emotion regulation and anger management skills as probable moderators to that relationship (Chemtob, Novaco, Hamada, Gross, & Smith, 1997). However, no study has investigated these interactive relationships with female-perpetrated physical IPV. Therefore, this study examined the interactive effects of PTSD symptoms, emotion regulation, and anger management skills on female-perpetrated physical IPV. Female community members (N = 254) completed measures of PTSD symptoms, emotion regulation strategies, anger management skills during partner conflict, and IPV perpetration. Results indicated two-way interaction effects between emotion regulation and both PTSD symptoms and negative partner attributions. In addition, PTSD symptoms, emotion regulation, and escalating strategies marginally interacted to predict female-perpetrated IPV. Implications of these results for future research and interventions are discussed.