Designing and Evaluating Opioid Misuse Prevention Training for Rural Communities and Health Care Providers.

Through Substance Abuse and Mental Health Services Administration funding, Michigan State University (MSU) Extension partnered with MSU's Family Medicine and Health Department of Northwest Michigan to implement trainings for community members and health care providers to increase awareness and improve prevention efforts addressing opioid use disorder (OUD) in rural areas. We formed the Michigan Substance Use Prevention, Education and Recovery (MiSUPER) project to design and evaluate opioid misuse prevention trainings. A socio-ecological prevention model was an underlying conceptual framework for this project and drove strategies used in trainings, products created, and measurement.

Three Cooperative Extension initiatives funded to address Michigan's opioid crisis.

People living with opioid use disorder and those experiencing other types of substance misuse are part of a public health crisis in the United States. Rates of opioid misuse, overdose, and opioid-related deaths within different subpopulations show where prevention efforts must focus. Through concerted efforts, aligned with common goals, a statewide community-based educational organization (Michigan State University Extension) has demonstrated ability to acquire multi-year funding from varied sources of state and federal funds that has produced robust support for statewide projects and collaborations.

Circuits for integrating learned and innate valences in the insect brain.

Animal behavior is shaped both by evolution and by individual experience. Parallel brain pathways encode innate and learned valences of cues, but the way in which they are integrated during action-selection is not well understood. We used electron microscopy to comprehensively map with synaptic resolution all neurons downstream of all mushroom body (MB) output neurons (encoding learned valences) and characterized their patterns of interaction with lateral horn (LH) neurons (encoding innate valences) in larva.

Useful road maps: studying Drosophila larva's central nervous system with the help of connectomics.

The larva of Drosophila melanogaster is emerging as a powerful model system for comprehensive brain-wide understanding of the circuit implementation of neural computations. With an unprecedented amount of tools in hand, including synaptic-resolution connectomics, whole-brain imaging, and genetic tools for selective targeting of single neuron types, it is possible to dissect which circuits and computations are at work behind behaviors that have an interesting level of complexity. Here we present some of the recent advances regarding multisensory integration, learning, and action selection in Drosophila larva.

Recurrent architecture for adaptive regulation of learning in the insect brain.

Dopaminergic neurons (DANs) drive learning across the animal kingdom, but the upstream circuits that regulate their activity and thereby learning remain poorly understood. We provide a synaptic-resolution connectome of the circuitry upstream of all DANs in a learning center, the mushroom body of Drosophila larva. We discover afferent sensory pathways and a large population of neurons that provide feedback from mushroom body output neurons and link distinct memory systems (aversive and appetitive).

Severe symptoms and very low quality-of-life among outpatients newly diagnosed with advanced cancer: data from a multicenter cohort study.

Purpose: The aim of this study was to identify symptoms of severe intensity or very low scores for quality of life (QoL) domains in newly diagnosed outpatients with advanced cancer.

Methods: This multicenter cohort study from a state-wide palliative care network included adult outpatients with advanced cancer diagnosed within the preceding 8 weeks from four comprehensive cancer centers (DRKS00006162, registered on 19 May 2014). We used the Palliative Outcome Scale (POS), Hospital Anxiety and Depression Scale, and European Organization for Research and Treatment of Cancer QoL Questionnaire-C30.

Connecting Primary Care to Community-Based Education: Michigan Physicians' Familiarity With Extension Programs.

Clinical-community linkages enhance health care delivery and enable physician-patient partnerships to achieve better health. The Michigan State University (MSU) Model of Health Extension includes a strategy for forming these linkages by focusing on increasing primary care patient referrals and enrollment in health programs. This article shares the results of a survey of Michigan internal medicine and family medicine physicians ( = 323) to better understand attitudes toward and familiarity with community-based education (CBE) programs and to assess the logistical requirements to make CBE referrals efficient and sustainable.

Memory enhancement by ferulic acid ester across species.

Cognitive impairments can be devastating for quality of life, and thus, preventing or counteracting them is of great value. To this end, the present study exploits the potential of the plant and identifies the constituent ferulic acid eicosyl ester [icosyl-(2)-3-(4-hydroxy-3-methoxyphenyl)-prop-2-enoate (FAE-20)] as a memory enhancer. We show that food supplementation with dried root material from dose-dependently improves odor-taste reward associative memory scores in larval and prevents the age-related decline of this appetitive memory in adult flies.

Functional architecture of reward learning in mushroom body extrinsic neurons of larval Drosophila.

The brain adaptively integrates present sensory input, past experience, and options for future action. The insect mushroom body exemplifies how a central brain structure brings about such integration. Here we use a combination of systematic single-cell labeling, connectomics, transgenic silencing, and activation experiments to study the mushroom body at single-cell resolution, focusing on the behavioral architecture of its input and output neurons (MBINs and MBONs), and of the mushroom body intrinsic APL neuron.

A longitudinal communication approach in advanced lung cancer: A qualitative study of patients', relatives' and staff's perspectives.

Communication and the care of patients with advanced cancer are a dynamic, interactive and challenging process, often characterised in every day practice by discontinuity and lack of coordination. The objective of this study was to explore the patients' and family-caregivers' needs and preferences regarding communication, quality of life and care over the trajectory of disease. The second aim was to assess health professionals' views on a longitudinally structured, forward-thinking communication approach based on defined milestones.

The complete connectome of a learning and memory centre in an insect brain.

Associating stimuli with positive or negative reinforcement is essential for survival, but a complete wiring diagram of a higher-order circuit supporting associative memory has not been previously available. Here we reconstruct one such circuit at synaptic resolution, the Drosophila larval mushroom body. We find that most Kenyon cells integrate random combinations of inputs but that a subset receives stereotyped inputs from single projection neurons.

The Olmpiad: concordance of behavioural faculties of stage 1 and stage 3 larvae.

Mapping brain function to brain structure is a fundamental task for neuroscience. For such an endeavour, the larva is simple enough to be tractable, yet complex enough to be interesting. It features about 10,000 neurons and is capable of various taxes, kineses and Pavlovian conditioning.

[Pain Management in Palliative Care].

A consistent pain management together with treatment of dyspnoea belongs to the main issues in symptom control in particular in palliative thoracic oncology. Together with the medicamentous therapy the psychologic and social circumstances of the affected patients have to be considered as factors influencing the experience of pain. The therapeutic fundament according to the WHO guideline for cancer pain is the opiate based medicamentous adjustment combined with non-opioids.

Pavlovian Conditioning of Larval : An Illustrated, Multilingual, Hands-On Manual for Odor-Taste Associative Learning in Maggots.

Larval offer a study case for behavioral neurogenetics that is simple enough to be experimentally tractable, yet complex enough to be worth the effort. We provide a detailed, hands-on manual for Pavlovian odor-reward learning in these animals. Given the versatility of for genetic analyses, combined with the evolutionarily shared genetic heritage with humans, the paradigm has utility not only in behavioral neurogenetics and experimental psychology, but for translational biomedicine as well.

Cooperative Extension as a Framework for Health Extension: The Michigan State University Model.

Problem: The Affordable Care Act charged the Agency for Healthcare Research and Quality to create the Primary Care Extension Program, but did not fund this effort. The idea to work through health extension agents to support health care delivery systems was based on the nationally known Cooperative Extension System (CES). Instead of creating new infrastructure in health care, the CES is an ideal vehicle for increasing health-related research and primary care delivery.

Randomized, double-blind, phase II trial comparing gemcitabine-cisplatin plus the LTB4 antagonist LY293111 versus gemcitabine-cisplatin plus placebo in first-line non-small-cell lung cancer.

Introduction: In this phase II study, patients with stage IIIB/IV non-small-cell lung cancer were randomly assigned (1:1:1) to receive LY293111 (200 mg twice daily [200 LY293111] or 600 mg twice daily [600 LY293111]) or placebo for 7 days, followed by concurrent cisplatin (75 mg/m2; day 1) and gemcitabine (1250 mg/m2; days 1 and 8), every 21 days.The primary endpoint was progression-free survival, (PFS), with 75% power to detect 33% improvement compared with placebo (5 months).

Methods: Of 200 randomized patients, 195 were treated.

The validation of estrogen receptor 1 mRNA expression as a predictor of outcome in patients with metastatic non-small cell lung cancer.

The prognostic role of estrogen receptors in lung cancer is not validated. Results from patients with early stage non-small lung cancer patients indicate a prognostic role of estrogen receptor 1 (ESR1) mRNA expression in these patients. Automated RNA extraction from paraffin and RT-quantitative PCR was used for evaluation of tumoral ESR1 and progesterone receptor (PGR) mRNA expression.

Prospective, multicenter, randomized, independent-group, open-label phase II study to investigate the efficacy and safety of three regimens with two doses of sagopilone as second-line therapy in patients with stage IIIB or IV non-small-cell lung cancer.

Introduction: Sagopilone is the first fully synthetic epothilone in clinical development and has proven preclinical activity in tumor models. This multicenter, randomized, open-label, phase II study examined the efficacy and safety of three regimens with two doses and two infusion durations of second-line sagopilone in pretreated patients with stage IIIB or IV non-small-cell lung cancer.

Methods: Eligibility criteria included: at least one measurable lesion by modified response evaluation criteria in solid tumors; World Health Organization performance status of 0 or 1; and failure of previous platinum-based chemotherapy.

A randomized phase II study of pemetrexed in combination with cisplatin or carboplatin as first-line therapy for patients with locally advanced or metastatic non-small-cell lung cancer.

Background: Pemetrexed plus cisplatin was approved for first-line treatment of non-small-cell lung cancer (NSCLC) in patients with nonsquamous histology after initiation of this study. This phase II study evaluated pemetrexed plus cisplatin and pemetrexed plus carboplatin as first-line treatments for stage IIIB/IV NSCLC.

Patients And Methods: The patients were randomized (1:1) to 2 parallel arms: pemetrexed (500 mg/m(2)) plus cisplatin (75 mg/m(2)) or pemetrexed (500 mg/m(2)) plus carboplatin (area under the curve 6) day 1 every 3 weeks (maximum, 6 cycles).

Topotecan/cisplatin compared with cisplatin/etoposide as first-line treatment for patients with extensive disease small-cell lung cancer: final results of a randomized phase III trial.

Introduction: This phase III study compared efficacy and safety of topotecan-cisplatin (TP) versus topotecan-etoposide (TE) versus cisplatin-etoposide (PE) in chemo-naïve extensive disease small-cell lung cancer patients.

Methods: Seven hundred and ninety-five previously untreated patients were randomly assigned to TP (topotecan 1mg/m IV, d1-5; cisplatin 75 mg/m IV, d5; n = 358), PE (cisplatin 75 mg/m IV, d1; etoposide 100 mg/m IV, d1-3; n = 345) or TE (topotecan 1mg/m IV, d1-5; etoposide 80 mg/m IV, d3-5; n = 92). Primary endpoint was superiority of TP compared with PE, with the possibility to switch to a noninferiority test.

Tasisulam sodium (LY573636 sodium) as third-line treatment in patients with unresectable, metastatic non-small-cell lung cancer: a phase-II study.

Introduction: Tasisulam sodium (hereafter referred to as tasisulam) is a novel anticancer compound that induces apoptosis and exhibits antiangiogenesis activity in a broad range of cancer models, including non-small-cell lung cancer (NSCLC).

Methods: Tasisulam was administered as a 2-hour infusion every 21 days as third-line treatment in patients with advanced (stage IIIB/IV) NSCLC.

Results: Thirty-two patients received a Cmax target dose of 420 µg/ml.

FoxO1 induces Ikaros splicing to promote immunoglobulin gene recombination.

Somatic rearrangement of immunoglobulin (Ig) genes is a key step during B cell development. Using pro-B cells lacking the phosphatase Pten (phosphatase and tensin homolog), which negatively regulates phosphoinositide-3-kinase (PI3K) signaling, we show that PI3K signaling inhibits Ig gene rearrangement by suppressing the expression of the transcription factor Ikaros. Further analysis revealed that the transcription factor FoxO1 is crucial for Ikaros expression and that PI3K-mediated down-regulation of FoxO1 suppresses Ikaros expression.

A phase II randomized study of cisplatin-pemetrexed plus either enzastaurin or placebo in chemonaive patients with advanced non-small cell lung cancer.

Objectives: Enzastaurin is a serine/threonine kinase inhibitor that targets protein kinase C and AKT pathways. Enzastaurin and pemetrexed demonstrated synergy in preclinical studies. This trial was designed to evaluate the safety and efficacy of first-line enzastaurin plus cisplatin-pemetrexed in advanced non-small cell lung cancer (NSCLC).

Associative learning between odorants and mechanosensory punishment in larval Drosophila.

We tested whether Drosophila larvae can associate odours with a mechanosensory disturbance as a punishment, using substrate vibration conveyed by a loudspeaker (buzz:). One odour (A) was presented with the buzz, while another odour (B) was presented without the buzz (A/B training). Then, animals were offered the choice between A and B.