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Abstract Introduction Migraine is a common disabling primary headache disorder characterized by attacks of severe pain, sometimes accompanied by symptoms including nausea and photo-/phono-phobia. Real-world data of patients with migraine who sufficiently (responders) and insufficiently (insufficient responders) respond to acute treatment (AT) are limited in China. This analysis explored whether responders to AT differ from insufficient responders in terms of clinical characteristics, treatment patterns, and patient-reported outcomes in China. Methods Data were drawn from the Adelphi Migraine Disease Specific Programme™, a point-in-time survey of internists/neurologists and their consulting patients with migraine, conducted in a real-world setting in China, January–June 2014. Responders and insufficient responders to prescribed AT were patients who typically achieved headache pain freedom within 2 h of AT in ≥ 4 and ≤ 3 of five migraine attacks, respectively. Responders were compared with insufficient responders; logistic regression was used to identify factors associated with insufficient response. Results Of 777 patients currently receiving AT, 44.0% were insufficient responders. Significantly fewer responders than insufficient responders had migraine with aura (13.1 vs. 23.8%; p = 0.0001). Responders reported a significantly lower mean Migraine Disability Assessment (MIDAS) total score (5.5 vs. 6.6; p = 0.0325). Responders reported a lower mean impairment while working (50.0 vs. 63.9%; p

Abstract Background Osteoarthritis (OA) is typically associated with pain, but many patients are not treated. Methods This point in time study explored factors associated with treatment status, using logistic regression of data from the Adelphi OA Disease Specific Programme conducted in the United States. Patients’ treatment status was based on physician-reported, current: 1) prescription medication for OA vs. none; and 2) physician treatment (prescription medication and/or recommendation for specified nonpharmacologic treatment for OA [physical or occupational therapy, acupuncture, transcutaneous electrical nerve stimulation, or cognitive behavior therapy/psychotherapy]) vs. self-management (no prescription medication or specified nonpharmacologic treatment). Results The 841 patients (including 57.0% knee OA, 31.9% hip OA) reported mild (45.4%) or moderate or severe (54.6%) average pain intensity over the last week. The majority were prescribed medication and/or recommended specified nonpharmacologic treatment; 218 were not prescription-medicated and 122 were self-managed. Bivariate analyses showed less severe patient-reported pain intensity and physician-rated OA severity, fewer joints affected by OA, lower proportion of joints affected by knee OA, better health status, lower body mass index, and lower ratings for cardiovascular and gastrointestinal risks, for those not prescribed medication (vs. prescription-medicated). Multivariate analyses confirmed factors significantly (p

ABSTRACT Listeria monocytogenes is a Gram-positive, facultative intracellular foodborne pathogen capable of causing severe, invasive illness (listeriosis). Three serotypes, 1/2a, 1/2b, and 4b, are leading contributors to human listeriosis, with 4b including the major hypervirulent clones. The multiplex PCR scheme developed by Doumith and collaborators employs primers targeting specific lineages (e.g., lineage II-specific lmo0737, lineage I-specific LMOf2365_2059) or serotypes (e.g., serotype 4b-specific LMOf2365_1900). The Doumith scheme (DS) is extensively employed for molecular serotyping of L. monocytogenes due to its high accuracy, relative ease, and affordability. However, for certain strains, the DS serotype designations are in conflict with those relying on antibody-based schemes or whole-genome sequence (WGS) analysis. In the current study, all 27 tested serotype 4b strains with sequence type 782 (ST782) within the hypervirulent clonal complex 2 (CC2) were designated 1/2b/3b using the DS. These strains lacked the serotype 4b-specific gene LMOf2365_1900, while retaining LMOf2365_2059, which, together with prs, yields the DS 1/2b/3b profile. Furthermore, 15 serotype 1/2a strains of four STs, mostly from water, were designated 1/2b/3b using the DS. These strains lacked the lmo0737 cassette but harbored genomic islands with LMOf2365_2059, thus yielding the DS 1/2b/3b profile. Lastly, we investigated a novel, dual 1/2a-1/2b profile obtained using the DS with 21 serotype 1/2a strains of four STs harboring both the lmo0737 cassette and genomic islands with LMOf2365_2059. The findings suggest that for certain strains and clones of L. monocytogenes the DS designations should be viewed with caution and complemented with alternative tools, e.g., traditional serotyping or WGS analysis. IMPORTANCE Listeria monocytogenes is a foodborne pathogen responsible for severe illness (listeriosis), especially in pregnant women and their fetuses, immunocompromised individuals, and the elderly. Three serotypes, 1/2a, 1/2b, and 4b, account for most human listeriosis, with certain serotype 4b clonal complexes (CCs) overrepresented in human disease. Serotyping remains extensively employed in Listeria epidemiologic investigations, and a multiplex PCR-based serotyping scheme is widely used. However, the PCR gene targets can be lost or gained via horizontal gene transfer, leading to novel PCR profiles without known serotype designations or to incorrect serotype assignments. Thus, an entire serotype 4b clone of the hypervirulent CC2 would be misidentified as serotype 1/2b, and several strains of serotype 1/2a would be identified as serotype 1/2b. Such challenges are especially common in novel clones from underexplored habitats, e.g., wildlife and surface water. The findings suggest caution in application of molecular serotyping, while highlighting Listeria’s diversity and potential for horizontal gene transfer.

Objectives Social determinants of health (SDoH) contribute to health outcomes. We identified SDoH that were modified by critical illness, and the effect of such modifications on recovery from critical illness.Design In-depth semistructured interviews following hospital discharge. Interview transcripts were mapped against a pre-existing social policy framework: money and work; skills and education; housing, transport and neighbourhoods; and family, friends and social connections.Setting 14 hospital sites in the USA, UK and Australia.Participants Patients and caregivers, who had been admitted to critical care from three continents.Results 86 interviews were analysed (66 patients and 20 caregivers). SDoH, both financial and non-financial in nature, could be negatively influenced by exposure to critical illness, with a direct impact on health-related outcomes at an individual level. Financial modifications included changes to employment status due to critical illness-related disability, alongside changes to income and insurance status. Negative health impacts included the inability to access essential healthcare and an increase in mental health problems.Conclusions Critical illness appears to modify SDoH for survivors and their family members, potentially impacting recovery and health. Our findings suggest that increased attention to issues such as one’s social network, economic security and access to healthcare is required following discharge from critical care.

Generation of transcriptional data has dramatically increased in the past decade, driving the development of analytical algorithms that enable interrogation of the biology underpinning the profiled samples. However, these resources require users to have expertise in data wrangling and analytics, reducing opportunities for biological discovery by ‘wet-lab’ users with a limited programming skillset. Although commercial solutions exist, costs for software access can be prohibitive for academic research groups. To address these challenges, we have developed an open source and user-friendly data analysis platform for on-the-fly bioinformatic interrogation of transcriptional data derived from human or mouse tissue, called Molecular Subtyping Resource (MouSR). This internet-accessible analytical tool, https://mousr.qub.ac.uk/, enables users to easily interrogate their data using an intuitive ‘point-and-click’ interface, which includes a suite of molecular characterisation options including quality control, differential gene expression, gene set enrichment and microenvironmental cell population analyses from RNA sequencing. The MouSR online tool provides a unique freely available option for users to perform rapid transcriptomic analyses and comprehensive interrogation of the signalling underpinning transcriptional datasets, which alleviates a major bottleneck for biological discovery. This article has an associated First Person interview with the first author of the paper.

Background : : We explored the association of anemia severity in patients with chronic kidney disease (CKD) and anemia treatment with work productivity in China. Methods : : Cross-sectional survey data from Chinese physicians and their CKD patients were collected in 2015. Physicians recorded demographics, disease characteristics, and treatment. Patients completed the Work Productivity and Activity Impairment questionnaire. Data were stratified by dialysis-dependence, hemoglobin (Hb) level, and anemia treatment. Results : : Based on data from 1,052 patients (704 non-dialysis-dependent [NDD] and 348 dialysis-dependent [DD] patients), prescribed anemia treatment differed significantly across Hb levels (P < 0.001). In NDD patients, anemia treatment also differed significantly by on-treatment Hb level (P < 0.001). In treated NDD patients with Hb < 10 g/ dL, Hb 10 to 12 g/dL, and Hb > 12 g/dL, 31%, 59%, and 38% of patients, respectively, were prescribed oral iron, and 34%, 19%, and 0% of patients, respectively, were prescribed oral iron with erythropoiesis-stimulating agents (ESA). NDD patients were less likely to be prescribed any anemia treatment, and ESA specifically, than DD patients. When treated, 67% and 45% of NDD and DD patients, respectively, had Hb ≥ 10 g/dL (P < 0.001). Overall work and activity impairment differed significantly across Hb levels in NDD and DD patients, with the least impairment observed at the highest Hb level. Conclusion : : Approximately 40% of NDD patients and 60% of DD patients receiving anemia treatment had Hb < 10 g/dL. Compared with mild anemia patients, severe anemia patients were more likely to be treated for anemia and have impaired work productivity. Chinese CKD patients could benefit from improved anemia treatment.

Abstract Background Real-world data on sufficient/insufficient response, and predictors of insufficient response, to acute treatments for migraine are limited in Japan. This study aimed to identify factors associated with insufficient response to acute treatment of migraine by exploring significant differences between people with migraine who sufficiently/insufficiently respond to prescribed acute treatment in Japan. Methods This was a retrospective analysis of 2014 Adelphi Migraine Disease Specific Programme cross-sectional survey data collected from physicians and their consulting adult patients with migraine in Japan. Insufficient responders to prescribed acute treatment were patients who achieved headache pain freedom within 2 h of acute treatment in no more than three of their last five migraine attacks. Factors associated with insufficient response to prescribed acute migraine treatment were identified using backward logistic regression. Results Overall, 227/538 (42.2%) patients were classified as insufficient responders to prescribed acute migraine treatment. Significantly more insufficient responders than sufficient responders had consulted a neurologist or a migraine/headache specialist, and had chronic migraine or medication-overuse or tension-type headaches (p

Abstract Background Migraine has a severe impact on health-related quality of life (HRQoL) affecting physical, emotional, and social aspects of daily living of an individual. Preventive treatment has been demonstrated to improve HRQoL by reducing the frequency of migraine headache days. Methods The study used data from 2017 Adelphi Migraine Disease Specific Program, which is a cross-sectional survey of physicians and their consulting patients with migraine in the United States (US) and five European countries (EU [Germany, France, UK, Italy and Spain]). Objectives were to evaluate patient-reported outcome (PRO) measures in the following two subgroups and by region (US and EU): (i) patients who are eligible for migraine preventive treatment (≥4 migraine headache days/month), and (ii) patients who are non-eligible for preventive treatment (

Abstract Background Migraine is a chronic, disabling neurological disease characterized by moderate-to-severe headache pain with other symptoms, including nausea, vomiting, and photophobia. Triptans, while generally effective, are insufficiently efficacious in 30–40% of patients and poorly tolerated by or contraindicated in others. We assessed the impact of insufficient response to triptans on health-related quality of life (HRQoL) and work productivity in patients currently receiving any prescribed triptan formulation as their only acute migraine medication. Methods Data were from the 2017 Adelphi Migraine Disease Specific Programme, a cross-sectional survey of primary care physicians, neurologists, and headache specialists and their consulting patients with migraine in the USA, France, Germany, Italy, Spain, and UK. Triptan insufficient responders (TIRs) achieved freedom from headache pain within 2 h of acute treatment in ≤3/5 migraine attacks; triptan responders (TRs) achieved pain freedom within 2 h in ≥4/5 attacks. Multivariable general linear model examined differences between TIRs and TRs in HRQoL and work productivity. Logistic regression identified factors associated with insufficient response to triptans. Results The study included 1413 triptan-treated patients (TIRs: n = 483, 34.2%; TRs: n = 930, 65.8%). TIRs were more likely to be female (76% vs. 70% for TIRs vs TRs, respectively; p = 0.011), older (mean age 42.6 vs. 40.5 years; p = 0.003), and had more headache days/month (7.0 vs. 4.4; p

Abstract Background Reductions in health-related quality of life (HRQoL) in patients with chronic kidney disease (CKD) are thought to be exacerbated by the low hemoglobin (Hb) levels that define anemia, a common complication of CKD. The current analysis evaluated the impact of anemia on HRQoL and work productivity in patients with non-dialysis dependent and dialysis-dependent CKD using real-world data. Methods Data were collected in France, Germany, Italy, Spain, the UK, the USA and China in 2012–2018 in the Adelphi Real World Disease Specific Programme™ for CKD, a large, cross-sectional, survey of physicians and their patients. Patients completed three patient-reported outcomes (PRO) instruments: the EuroQol 5-Dimension 3-level (EQ-5D-3 L), the Kidney Disease Quality of Life (KDQOL-36) instrument and the Work Productivity and Activity Impairment questionnaire. PROs were assessed by CKD stage and Hb levels, and regression analyses were performed with CKD stage and Hb level as independent variables and PROs as outcome variables, while adjusting for age, sex, CKD stage, comorbidities and cardiovascular risk. Results Overall, 5276 patients participated in the survey, including 28% stage 4 and 36% dialysis patients. Patients with lower Hb levels more often reported problems/issues on all EQ-5D-3 L domains (p

Summary: Background: Gender differences in life expectancy and societal roles have implications for a country's capacity to support its older population. Specifically, the longevity risk associated with longer life expectancy of women, with greater risk of morbidity entails different needs between genders in older age. We aimed to quantify gender differences in the ageing experience of older people in Organization for Economic Cooperation and Development (OECD) countries as a first step in identifying policy gaps and differences in the allocation of resources and social support for older men and women. Methods: We constructed a multidimensional Ageing Index to account for gender differences in societal ageing, using mostly gender-disaggregated latest available data between 2015 and 2019, for 18 OECD countries. Our Ageing Index is a weighted sum of scores for five domains, which consisted of various measures, that are important for societal ageing: wellbeing, productivity and engagement, equity, security, and cohesion. The construction of the domains and their relative weighting was determined by the Research Network on an Ageing Society, an interdisciplinary group of academics. We computed the overall index and domain scores (from 0 to 100) for each gender and compared these scores between genders and countries. Findings: In every country, gender differences in key domains of societal ageing favour men. Countries in northern Europe (ie, Denmark, Sweden, Finland and Norway), the Netherlands, and Japan had high overall Index scores for both genders, whereas many eastern and southern European countries (eg, Hungary, Poland, and Slovenia) performed less well. Countries with the largest gender difference in Index scores include the Netherlands, Germany, and Italy, whereas Ireland, Spain, and Poland had the smallest difference. Gender differences were present for the domains of productivity and engagement, security, and cohesion. Gender differences favoured men for domain productivity and engagement (mean 10·2, 95% CI 7·8–12·6; p

Abstract Background In Japan, detailed information on the characteristics, disease burden, and treatment patterns of people living with migraine is limited. The aim of this study was to compare clinical characteristics, disease burden, and treatment patterns in people with episodic migraine (EM) or chronic migraine (CM) using real-world data from clinical practice in Japan. Methods This was an analysis of data collected in 2014 by the Adelphi Migraine Disease Specific Programme, a cross-sectional survey of physicians and their consulting adult patients in Japan, using physician and patient questionnaires. We report patient demographics, prescribed treatment, work productivity, and quality-of-life data for people with CM (≥15 headache days/month) or EM (not fulfilling CM criteria). In descriptive analyses, continuous and categorical measures were assessed using t-tests and Chi-squared tests, respectively. Results Physicians provided data for 977 patients (mean age 44.5 years; 77.2% female; 94.5% with EM, 5.5% with CM). A total of 634/977 (64.9%) invited patients (600 with EM; 34 with CM) also provided data. Acute therapy was currently being prescribed in 93.7% and 100% of patients with EM and CM, respectively (p = 0.069); corresponding percentages for current preventive therapy prescriptions were 40.5% and 68.5% (p

OBJECTIVE: To determine how osteoarthritis (OA) severity correlates with self-reported outcomes relevant from the patient’s perspective in the Italian clinical setting. METHODS: Data were drawn from the 2017-18 Adelphi OA Disease Specific ProgrammeTM (DSP). Data were collected in the Italian clinical practice settings by primary care physicians, rheumatologists, orthopedists, and their patients with OA, during their regular office visits. Physicians completed information about OA-related visits to healthcare professionals (HCPs), tests/scans conducted, emergency room (ER) visits, surgeries, and OA-related treatment. Physicians also rated patients’ functioning on a 0 to 10 scale (0 = fully functional; 10 = completely impaired). Outcomes included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, functional limitations, treatment needs, EuroQoL-5 Dimension (EQ-5D) visual analogue scale (VAS), the work productivity and activity impairment. Descriptive statistics (numbers and percent for categorical variables; means with standard deviations [SD] for continuous variables) were used to evaluate the different variables as appropriate. RESULTS: The study population comprised 900 patients from Italy with knee (40.9%), back (38.7%), hip (27.9%), and/or shoulder (20.3%) OA. Mean age was 66.6 years with a prevalence of female (63%) patients. Patients had mild (26%), moderate (54%), severe (20%) disease severity. Patients with severe disease reported higher functional limitations, greater use of treatments, reduced quality of life, and impaired work productivity and activity. The burdens were higher among elderly and obese patients and in patients with highest pain severity score. CONCLUSIONS: The results from this cross-sectional study show the impact of OA disease severity on all dimensions of health-related quality of life (HRQoL), as well as in OA-related health care resource use.

IntroductionMillions of Americans are admitted to the intensive care unit (ICU) per year. Many survivors of the ICU will experience posttraumatic stress disorder (PTSD); although volumetric hippocampal and amygdala studies have been conducted in other trauma survivors (i.e., veterans), the association between PTSD symptoms and hippocampal and amygdala volumes in ICU survivors has not been described. We hypothesize that the severity of posttraumatic stress symptoms in ICU survivors is associated with lower volumes of both the hippocampus and amygdala at 3 and 12 months.MethodsSecondary analysis of the VISIONS study, a prospective sub-study of the BRAIN-ICU cohort, which included survivors of critical illness. The PTSD Checklist Specific was used at 3 and 12 months to evaluate the ICU as a traumatic experience. A Philips Achieva 3T MRI scanner was used to scan patients at both discharge and 3 months. To compare median brain volumes at discharge and 3 months for those with and without PTSD symptomatology, we used a Kruskal–Wallis (KW) test.ResultsAt 3 month follow up, three patients had PTSD symptomatology and N = 1 at 12 month follow up. There was no difference between median brain volumes (hippocampus or amygdala) between individuals with PTSD symptomatology at either 3 or 12 months (p-values > 0.05).DiscussionAlthough our study did not reveal significant differences in brain volumes between PTSD patients and non-PTSD patients, sample size was a major limitation and larger scale studies should be undertaken to elucidate possible neurobiological markers of PTSD in ICU survivors.

OBJECTIVES/GOALS: To explore the severity of posttraumatic stress disorder (PTSD) symptoms in association with hippocampal and amygdala volumes in ICU survivors. We hypothesize that the severity of posttraumatic stress symptoms in ICU survivors is associated with lower volumes of both the hippocampus and amygdala. METHODS/STUDY POPULATION: Secondary analysis of the VISIONS study, a prospective sub-study of the BRAIN-ICU cohort, which included survivors of critical illness. Patients were screened for preexisting PTSD before discharge. The PTSD Checklist Specific (PCL-S) was used at 3 and 12 months to evaluate the ICU as a traumatic experience. A score of >30, indicated significant symptoms of PTSD. A Philips Achieva 3T MRI scanner was used to scan patients at both discharge and 3-month follow-up. To compare median brain volumes at discharge and 3 months for those with and without significant PTSD symptomatology (PCL-S ≥30) at 3 and 12 months, we used a Kruskal-Wallis (KW) equality-of-populations rank test. RESULTS/ANTICIPATED RESULTS: The median age for our sample was 58.5 (52.6, 63.7). One-third of the sample was female, and 90% were Caucasian. Fifty-seven percent of individuals (N = 12) had at least one prior mental health diagnosis, with two having a prior history of PTSD. One third of individuals experienced delirium during their critical illness. At 3-month follow up, there were three patients with PTSD symptomatology and one at 12-month follow up. Median brain volumes (hippocampus or amygdala) did not differ between individuals with or without PTSD symptomatology at either 3 or 12 months (p-values for all tests >0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Although our study did not reveal significant differences in brain volumes between PTSD patients and non-PTSD patients, sample size is a major limitation and larger scale studies should be undertaken to elucidate possible neurobiological markers of PTSD in ICU survivors. CONFLICT OF INTEREST DESCRIPTION: Dr. Wilson would like to acknowledge salary support from the Vanderbilt Faculty Research Scholars Program (1KL2TR002245), HL111111 and GM120484. Drs. Ely and Jackson as well as Mrs. Kiehl all receive funding for their time working on this investigation from AG035117 and HL111111. Dr. Ely would additionally like to acknowledge salary support from the Tennessee Valley Healthcare System Geriatric Research Education and Clinical Center (GRECC). Dr. Ely will also disclose additional funding for his time from AG027472 and having received honoraria from Orion and Hospira for CME activity; he does not hold stock or consultant relationships with those companies. The authors would like to acknowledge the following: this work was conducted in part using the resources of the Center for Computational Imaging at Vanderbilt University Institute of Imaging Science and the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN, and study data were collected and managed using REDCap electronic data capture tools hosted at Vanderbilt University.

A sucessão de eventos após a revegetação de uma área, em geral, não é estudada. Com o passar do tempo, um consórcio vegetal que se apresentou favorável na fase inicial pode não ser adequado no futuro, deixando a área com o solo descoberto e suscetível à ação dos fatores intempéricos. O objetivo deste trabalho foi monitorar características associadas à contenção vegetativa e, em longo prazo, o surgimento de novas formas de cobertura ou exposição do solo em resposta à revegetação com gramíneas e leguminosas em talude rodoviário de declividade acentuada. Após quatro anos, foi observada, nas parcelas experimentais, a presença de novas formas de cobertura ou exposição do solo, denominadas tipologias, como: cobertura de braquiária, leguminosa, capim-gordura, espécies invasoras, biomanta, resíduos em decomposição, crostas microfíticas, crosta física, solo exposto, erosão e afloramento de rochas. Essas tipologias foram quantificadas em dois levantamentos: antes e após o período chuvoso. Foram confeccionados mapas de cobertura para cada parcela experimental e analisadas a dinâmica, distribuição espacial, frequência e competição entre as tipologias encontradas nos dois levantamentos. Das 11 tipologias encontradas, as espécies vegetais e as crostas microfíticas foram as mais importantes no estádio primário da sucessão ecológica, resultando em rápida estabilização e recuperação da superfície degradada e favorecendo o aparecimento de espécies invasoras. A variação sazonal entre os dois levantamentos levou à diminuição da erosão e ao solo exposto, pelo incremento da cobertura vegetal e das crostas microfíticas.

Rural producer development or integration programs in Brazil are partnerships between industries and farmers that have been practiced since the 70's in Brazil. These models emerged from the need for dependable supply of raw materials produced on family farms, principally tobacco growing and pig farming. In the forestry sector, most of these programs emerged in the 80's. To date, these partnerships have attracted a growing number of producers given the advantages offered, especially a guaranteed income. Thus, the object of this research was to investigate the principal programs of rural producer development and integration in Brazil and compare their benefits. The main programs are from industries of tobacco cultivation, pig farming, poultry raising and forestry. It was observed that these programs have benefited farmers, mainly improving the quality of their production because of technical specifications and requirements. It is concluded that beyond the technical expertise, these programs provide benefits to society, given that contracts increasingly require the achievement of legal requirements and other matters related to environmental and social concerns.

Fatty acid binding protein-4 (FABP4) and FABP5 are two closely related FA binding proteins expressed primarily in adipose tissue and/or macrophages. The small-molecule FABP4 inhibitor BMS309403 was previously reported to improve insulin sensitivity in leptin-deficient Lepob/Lepob (ob/ob) mice. However, this compound was not extensively characterized in the more physiologically relevant animal model of mice with diet-induced obesity (DIO). Here, we report the discovery and characterization of a novel series of FABP4/5 dual inhibitors represented by Compounds 1–3. Compared with BMS309403, the compounds had significant in vitro potency toward both FABP4 and FABP5. In cell-based assays, Compounds 2 and 3 were more potent than BMS309403 to inhibit lipolysis in 3T3-L1 adipocytes and in primary human adipocytes. They also inhibited MCP-1 release from THP-1 macrophages as well as from primary human macrophages. When chronically administered to DIO mice, BMS309403 and Compound 3 reduced plasma triglyceride and free FA levels. Compound 3 reduced plasma free FAs at a lower dose level than BMS309403. However, no significant change was observed in insulin, glucose, or glucose tolerance. Our results indicate that the FABP4/5 inhibitors ameliorate dyslipidemia but not insulin resistance in DIO mice.

Este estudo analisou os fatores que contribuem para a relação de confiança no Programa de Fomento Florestal de indústria de celulose e produtores rurais fomentados em Minas Gerais. Foram aplicados 141 questionários a produtores rurais fomentados, em 32 municípios de sete microrregiões mineiras. A amostragem foi aleatória estratificada, sendo os critérios: a) Produtor Fomentado com Contrato Finalizado (PFCF) composto por produtores que possuíam pelo menos um contrato encerrado com a indústria de celulose; e b) Produtor Fomentado com Contrato em Andamento (PFCA) composto por produtores que não haviam finalizado nenhum contrato de fomento com a indústria de celulose. Os produtores fomentados realizam contrato de fomento florestal para apenas a primeira rotação. Assim, legalmente possuem a obrigatoriedade de entrega de 97% da madeira do primeiro ciclo da floresta. Entretanto, referente ao segundo ciclo não contratado da floresta, 18% dos produtores fomentados disseram ter interesse na comercialização dessa madeira com a empresa, indiferente de variações em preços de produtos concorrentes, como o carvão vegetal. Acredita-se que, não havendo oscilações significativas nesses mercados concorrentes, 50% dos fomentados devem comercializar o segundo corte com a empresa fomentadora. Atualmente, em 98,4% dos contratos realizados com produtores rurais fomentados há cumprimento de ambas as partes nos acordos firmados. A confiança e confiabilidade no relacionamento entre indústria de celulose e fomentados foram confirmadas, mas existem alguns fatores que contribuem para a possível desconfiança no fomento florestal, como: o sistema de medida da madeira, o custo de transporte e a ausência de política de preços que favorecem o entendimento dos produtores fomentados.This study analyzed factors that contribute to relations of trust within a private woodlot producer program managed by a cellulose industry in Minas Gerais state. One hundred and forty one questionnaires were completed by interviewing small woodlot rural producers that participate in 32 municipalities within 7 of the state's microregions. The sampling was performed by random stratification according to the following criteria: a) Woodlot Producers with Completed Contract (PFCF) who have finished at least one contract with the cellulose firm and b) Woodlot Producers with Contract in Progress (PFCA) who have not yet completed a contract. In general, the program's woodlot producers will sign contracts only for the first forest cut. This means that they are obligated to deliver to the company 97% of the wood from the first cycle of production. However, for the second cycle, 18% of those interviewed showed interest in selling their wood to the cellulose firm regardless of whatever price variations might occur for competing forest markets such as for charcoal. If no significant fluctuations occur in these competing markets it is possible that as many as 50% of woodlot producers might sell their second cut to the cellulose firm. Once rural producers sign on to the program, 98.4% of them complete their contractual obligations. Trust and trustworthiness were confirmed as existing in relationships between the cellulose firm and woodlot producers. However, there are some factors in the woodlot program that contribute to mistrust, including the wood measurement system, transport costs and the absence of a pricing policy easily understood by woodlot producers.

O setor florestal tem exercido importante papel no desenvolvimento socioeconômico das regiões produtoras de madeira. Os benefícios são atribuídos à geração de renda (alternativa para pequenos e médios produtores rurais), impostos, divisas e incremento no PIB. As novas exigências do mercado, em termos de competitividade, levaram as empresas a criarem os programas de fomento florestal como forma de expandir a oferta de madeira e garantir sua base produtiva. Nesse contexto, surge a necessidade de se identificarem os fatores que determinam a realização de novos contratos de fomento florestal. A amostra estudada foi composta pelos produtores rurais da mesorregião do Vale do Rio Doce, Minas Gerais, que realizaram pelo menos um contrato de fomento entre os anos de 1995 e 2006. Os dados foram coletados por meio de questionários semiestruturados no ano de 2006. Para identificar os fatores, utilizou-se a Análise Estatística Multivariada, especificamente a técnica de análise de discriminante. Os resultados apontaram que o sistema de medição da madeira (SISMED), a área contratada (ACONTRAT) e o tamanho da propriedade (TAMPROP) foram, nessa ordem, os principais determinantes para a realização de novos contratos. Desse modo, sugere-se que as empresas florestais desenvolvam programas de acompanhamento técnico e formação dos produtores fomentados, no intuito de reduzir as desconfianças no SISMED e aumentar o volume de áreas plantadas por meio do fomento.The forestry sector has played an important role in the socio-economic development of wood-producing regions. Benefits include private income (an alternative for small and medium-sized rural producers), government tax income, balance of payment advantages, and increasing GNP. New market demands in terms of competitiveness have led cellulose companies to create private woodlot programs as a way to expand timber supplies and guarantee a productive basis. Within this context, arises the need to identify determinant factors for signing new private woodlot contracts. The sample studied is composed of rural producers who signed at least one contract in the Vale do Rio Doce meso region in Minas Gerais in 1995-2006.Data were collected in 2006 using a semi-structured questionnaire. Factors were identified using a multivariate statistical analysis, specifically applying a discriminate analysis technique. Results indicate that the system used by the company to measure timber (SISMED), contracted area size (ACONTRAT) and property size (TAMPROP) are, in this order, the principal determinants for assuming new contracts. Based on the study results, it is suggested that forestry companies further develop technical monitoring and training for woodlot producers. These programs could reduce the present lack of confidence indicated for the SISMED factor and help increase the amount of areas planted.

Considerando que o Brasil e muitos outros países tropicais necessitam de aperfeiçoar métodos de recobrimento de taludes, tornam-se necessários estudos que aprimorem a utilização e a eficácia das diferentes alternativas do mercado. Este estudo teve como objetivo avaliar o desempenho das geomantas comerciais antierosivas MacMat®, Fibrax® e Tela Biotêxtil® na proteção do solo contra a erosão superficial hídrica. O experimento foi realizado em um talude em corte de estrada na cidade de Viçosa (MG), em meados de 2003, e foi avaliado entre dezembro e março de 2004. Para isso, realizou-se uma análise do escoamento superficial baseada em oito eventos chuvosos comparando-se as variáveis massa de sólidos e volume de suspensão de água + solo escoado em uma combinação de geomantas com ou sem vegetação (mistura de espécies de gramíneas e leguminosas). Os tratamentos testados foram: Tratamento 1 - testemunha (solo exposto); Tratamento 2 - Tela Biotêxtil® com plantas; Tratamento 3 - MacMat® sem plantas; Tratamento 4 - MacMat® com plantas; Tratamento 5 - Fibrax® sem plantas; e Tratamento 6 - Fibrax® com plantas. A análise estatística utilizada foi o teste de Tukey a 5 %. Embora não tenham sido encontradas diferenças significativas entre os tratamentos aplicados devido ao elevado coeficiente de variação, pode-se constatar que a utilização das mantas proporcionou a redução da perda de solos. O tratamento seis foi o mais eficiente para impedir a perda de solo. Entretanto, quando esta geomanta foi utilizada sem vegetação (Tratamento 5), permitiu o maior volume de suspensão escoada. Concluiu-se que as geomantas aumentaram a proteção do solo contra a erosão superficial hídrica e a incorporação de vegetação melhorou os resultados em todos os tratamentos.Considering that Brazil and many other countries with tropical ecosystems need to enhance methods of embankment cover, it is necessary to study the enhancement of available erosion control means. The study objective was to evaluate the efficiency of three commercial erosion mats: MacMat®, Fibrax® and Tela Biotêxtil® in rainfall surface erosion protection. The experiment was carried out between December 2003 and March 2004 on an embankment of a road section in Viçosa, Minas Gerais State, Brazil. Surface runoff from the experimental area was analyzed based on eight rainfall events and data of the following variables: solid mass and volume of suspended soil + water runoff. These data were compared in relation to geotextiles with or without vegetation (a mixture of grass and legume species). The treatments were: Treatment 1 - Control (exposed soil); Treatment 2 - Tela Biotêxtil® with plants; Treatment 3 - MacMat® without plants; Treatment 4 - MacMat® with plants; Treatment 5 - Fibrax® without plants and Treatment 6 - Fibrax® with plants. The Tukey test was used at 5% for the statistical analysis. Although no significant differences were found among treatments due to the high variation coefficient, it was obvious that erosion mats generally reduce soil loss. Treatment 6 was the most efficient. The volume of suspended soil + water runoff was however highest in Treatment 5 (mat without plants). The erosion mats enhanced soil protection against surface erosion by rainwater; vegetation planting along with the mats improved results for all treatments.

Este estudo teve como objetivo caracterizar o banco de sementes de um fragmento florestal na região de Viçosa, MG, bem como inferir se esse indicador pode garantir a sustentabilidade caso seja utilizado para recuperação de áreas degradadas e, ainda, comparar sua composição florística com aquelas descritas em outros estudos com bancos de sementes. Para isso, foram coletadas 20 amostras do banco de sementes em pontos escolhidos ao acaso, sendo cada amostra composta de quatro subamostras. Para a instalação do experimento no viveiro, foram utilizadas 20 caixas de madeira no formato de 50 x 50 x 15 cm. Após 90 dias, encontraram-se 508 indivíduos, dos quais foram identificadas 38 espécies, pertencentes a 34 gêneros e distribuídas em 22 famílias. O índice de diversidade (H') foi de 2,11; já a eqüabilidade (J) de 0,67 foi considerada alta quando comparada com as de outros bancos de sementes. Cecropia hololeuca (28,91%) e Solanum erianthum (18,67%) foram as espécies mais importantes e que podem atuar diretamente na dinâmica do processo de regeneração da mata. Verificou-se, portanto, que o banco de sementes estudado pode atuar na recomposição da vegetação de uma área degradada em condições semelhantes ao fragmento estudado, agilizando e garantindo a dinâmica do processo sucessional.Considering its potential use in degraded environments, this study characterized the composition of a seed bank obtained from an area of typical secondary succession on the Federal University of Viçosa campus. Inferences were made whether this indicator reflects future sustainability, given the seed bank's potential for revegetating degraded sites. Its floristic composition was compared with indices obtained in other similar seed bank studies. The specific site is located at the Mata da Garagem woods, a 40-year old forest fragment covering a low ridge parallel to a campus roadway. Twenty seed bank samples were collected from randomly selected points, each sample consisting of four subsamples. The experiment was installed on the campus nursery using 20 wooden boxes (50x50x15cm). After 90 days, 508 individual plants were counted, and 38 species were identified, as belonging to 34 genera distributed among 22 families. The diversity index (H') is 2.11; whereas the equability (J) value of 0.67 is considered high compared to other seed bank studies. Cecropia hololeuca (28.9%) and Solanum erianthum (18,7%) are indicated as the most important species within the forest regeneration process. Results suggest that the seed bank studied indeed has the potential for promoting and guaranteeing an ecological succession process dynamics on degraded lands of similar ecosystems.

Este estudo teve como objetivo avaliar o comportamento do enriquecimento no sistema solo orgânico-serapilheira, com sementes de espécies arbóreas nativas, para revegetação de áreas degradadas. O trabalho foi conduzido em casa de sombra e em bancadas a pleno sol, no Viveiro de Pesquisas do Departamento de Engenharia Florestal, situado no Campus da Universidade Federal de Viçosa (UFV). No levantamento do banco de sementes, foram encontrados 508 indivíduos, dos quais foram identificadas 38 espécies, pertencentes a 34 gêneros e distribuídas em 22 famílias. As avaliações da germinação das sementes introduzidas e do banco de sementes indicaram não haver diferença entre os ambientes testados (sombreado e a pleno sol). O crescimento das mudas, tanto das espécies provenientes dos propágulos contidos na serapilheira e no solo orgânico quanto das espécies utilizadas no enriquecimento, foi maior no ambiente sombreado. Os solos não adubados tiveram maior porcentual de sementes germinadas em relação aos solos adubados. A adubação dos substratos foi fundamental para o crescimento das mudas. Os resultados, portanto, demonstraram a eficiência do enriquecimento do banco de sementes e confirmaram o potencial dessa técnica para revegetação de áreas degradadas.This study evaluated the behavior of an organic soil-litter system seeded with native species with implications for revegetation of disturbed lands. The experiment was carried out in a greenhouse and on benches exposed to open sunlight at the Research Nursery of the Department of Forestry of the Universidade Federal de Vicosa (UFV). The inventory identified 508 individuals, out of which 38 species were identified, belonging to 34 genera and distributed among 22 families. Evaluation of both introduced seeds and seed bank did not show any differences in germination for the environmental regimes tested. Seedling growth for species originating from litter and topsoil propagules and for species inserted for enrichment was greater under shade. Unfertilized soils had a higher percentage of germinated seeds than fertilized soils. Fertilization was shown to be fundamental for seedling growth. Hence, results demonstrate improved efficiency by enriching a seed bank and confirm the potential of this technique for revegetation of disturbed lands.

Valproic acid (VPA) can autoinduce its own metabolism. Cases requiring VPA doses >4000 mg/day to obtain therapeutic plasma concentrations, such as these 3 cases, have never been published. Case 1 received VPA for seizures and schizophrenia and had >50 VPA concentrations in 4 years. A high dose of 5,250 mg/day of VPA concentrate was prescribed for years but this dose led to an intoxication when switched to the enterocoated divalproex sodium formulation, requiring a normal dose of 2000 mg/day. VPA metabolic capacity was significantly higher (t=-9.6; df = 6.3, p4 years with 137 VPA concentrations. To maintain VPA concentrations ≥50 μg/mL, VPA doses increased from 3,375 to 10,500 mg/day. In Cases 2 and 3, the duration of admission and the VPA dose were strongly correlated (r around 0.90; p

As atividades de extração de areia são de grande importância para o desenvolvimento social, mas igualmente responsáveis por impactos ambientais negativos, alguns inclusive irreversíveis. Nesse sentido, este trabalho teve como objetivo central avaliar qualitativamente os impactos ambientais decorrentes desse tipo de empreendimento. A identificação e caracterização qualitativa dos impactos ambientais foram feitas, utilizando-se o método do ";check-list";. Os resultados por meio do método do ";check-list"; possibilitaram identificar 49 impactos, sendo 36 negativos (73,47%) e 13 positivos (26,53%). A principal conclusão é a de que este estudo pode ser utilizado como referencial teórico para subsidiar o processo de licenciamento ambiental desse tipo de empreendimento.Sand extraction activities are of great importance for social development, however they are also responsible for negative and sometimes irreversible environmental impacts. In this context, this study aimed mainly at the qualitative evaluation of environmental impacts entailed by this kind of enterprise. The check-list method was used for the identification and qualitative characterization of environmental impacts. A number of 49 impacts were identified by the obtained results, 36 of which were negative (73,47%), and 13 positive (26,53%). The most important conclusion was that this study can serve as a theoretical reference to support the process of environmental licensing of projects in these types of enterprises.

A área do Retiro-Branco, de propriedade da Companhia Geral de Minas, subsidiária da ALCOA Alumínio S.A., foi minerada para a extração de bauxita de 1978 até 1981. Em 1982/1983, essa área teve seu processo de reabilitação implementado mediante a hidrossemeadura de gramíneas e leguminosas e o plantio puro de Mimosa scabrella Bentham. Em 1997 foi realizado o primeiro inventário da regeneração natural do Retiro-Branco, aravés da implantação de 19 parcelas permanentes para caracterização inicial do processo de sucessão natural. E em 2000 foi realizado o segundo inventário dessas parcelas para caracterizar o processo de dinâmica da regeneração, o objeto deste trabalho. O processo de dinâmica da regeneração natural foi caracterizado mediante análises quantitativas e qualitativas da distribuição diamétrica. Os estudos indicaram que o monitoramento mediante inventário florestal contínuo, com parcelas permanentes setorizadas, é uma ferramenta viável para avaliações da dinâmica da regeneração natural, rumo à compreensão dos caminhos da sucessão. Foi caracterizado o processo de estratificação da regeneração natural, em que as espécies pioneiras e clímax foram as principais componentes do estrato inferior e as secundárias, as principais componentes do estrato superior. O povoamento florestal do Retiro-Branco está sobre intensa atividade de estruturação, caracterizando o estágio inicial do processo de sucessão. As espécies secundárias são as de maior dominância nas maiores classes de altura e de diâmetro, sendo as principais responsáveis pela edificação do estrato superior. A prognose da distribuição diamétrica, realizada mediante o emprego da Cadeia de Markov, foi uma ferramenta de fácil implementação e que permitiu prever o caminho do processo de sucessão para o povoamento todo e para os grupos ecológicos de espécies, ampliando o entendimento dos mecanismos que regem o comportamento interno da sucessão.Retiro-Branco mine, a property of Companhia Geral de Minas, subsidiary of ALCOA Alumínio S.A., underwent bauxite extraction from 1978 to 1981. In 1982/1983 as part of its mine rehabilitation strategy, herbaceous species were hydroseeded and tree seedlings of Mimosa scabrella Bentham planted in the mining site. In 1997, 19 sample plots (50m²) were established in this area for the initial characterization of the natural regeneration process. In 2000, a second inventory was performed in the same plots to characterize natural regeneration dynamics. The process of natural regeneration dynamics was characterized through quantitative and qualitative analyses of diameter distribution. These studies demonstrated that using continuous forest inventory with a sample plot grid is a viable tool for evaluating natural regeneration dynamics. The stratification process for natural regeneration was characterized. Pioneer and climax species are the main components of the inferior stratum and the secondary ones the main component of the superior stratum. Retiro-Branco forest was found to be undergoing intense structuring activity, characterizing initial stage of succession. Secondary species are the most dominant in classes with greatest height and diameter, being the most responsible for the superior stratum construction. Diameter distribution prediction using Markov Matrix proved to be a simple way for foreseeing both the succession process of natural regeneration and future ecological groupings of species, increasing the understanding of mechanisms that rule internal succession behavior.

Como estratégia de reabilitação de área minerada foram realizados, no ano agrícola 1982/1983, hidrossemeadura de gramíneas e leguminosa e o plantio puro de Mimosa scabrella Bentham em Poços de Caldas, MG. Em 1997 foi implantado um conjunto de 19 parcelas permanentes de 50 m² nessa área, para caracterização inicial do processo de regeneração natural. Em 2000, foi realizado o segundo inventário nas parcelas, para caracterização do processo de dinâmica da regeneração natural, que é o objeto deste trabalho. O processo de dinâmica da regeneração natural foi caracterizado mediante análises quantitativas e qualitativas da composição florística e da estrutura horizontal e vertical. O povoamento florestal do Retiro-Branco está sobre intensa atividade de estruturação, caracterizando o estágio inicial do processo de sucessão. O declínio do povoamento puro de Mimosa escabrella está modificando a ordem anteriormente estabelecida para o processo de sucessão da área, provocando a diversificação de condições de sítio e, assim, selecionando a ocupação deste em função dos grupos ecológicos, sendo as espécies pioneiras as mais favorecidas. As espécies secundárias são as de maior dominância nas maiores classes de altura e de diâmetro, sendo as principais responsáveis pela edificação do estrato superior, em especial a espécie Miconia sellowiana. As espécies que apresentaram melhor desempenho na colonização e estruturação da regeneração natural do Retiro-Branco, nos dois inventários, foram Miconia sellowiana, Psychotria sessilis, Leandra melastomoides, Clethra scabra, Myrsine umbellata, Miconia pepericarpa, Tibouchina candolleana, Cordia superba, Cestrum amictum, Alchornea triplinervia, Casearia sylvestris, Blepharocalyx salicifolius, Myrcia rostrata e Schinus terebinthifolius, sendo indicadas como espécies para uso nos programas de reabilitação de áreas mineradas em condições semelhantes sobre a estratégia sucessional.As part of mine rehabilitation strategy, herbaceous species hydroseeding and Mimosa scabrella Bentham seedling planting was carried out in 1982/1983 the Retiro-Branco bauxite mine site. In 1997, 19 sample plots of 50m² were established for initial characterization of the natural regeneration process. In 2000, a second inventory was performed in those same sample plots, to characterize natural regeneration dynamics. This process was characterized by means of quantitative and qualitative analyses of floristic composition and horizontal and vertical structures. The forest succession at Retiro-Branco was found to be undergoing intense restructuring activity, characterizing initial stage of succession. The decline of Mimosa scabrella pure stands is modifying the successional order that previously occurred in this area, causing diversity in site conditions. Occupation of these sites occurs by ecological groups, pioneer species being favored in the process. Secondary species, especially Miconia sellowiana, dominate the classes with greatest height and diameter, and are the most responsible for construction of the superior stratum. Species which presented the best performance in colonization and structuring of natural regeneration at Retiro-Branco for both inventories were Miconia sellowiana, Psychotria sessilis, Leandra melastomoides, Clethra scabra, Myrsine umbellata, Miconia pepericarpa, Tibouchina candolleana, Cordia superba, Cestrum amictum, Alchornea triplinervia, Casearia sylvestris, Blepharocalyx salicifolius, Myrcia rostrata and Schinus terebinthifolius. These are indicated as promising species for rehabilitation programs of mined areas with similar conditions of sucessional strategy.

O presente estudo foi desenvolvido com o objetivo de contribuir para a compreensão do "ambientalismo empresarial" do setor florestal brasileiro, particularmente sua relação com os sistemas voluntários de certificação florestal, identificando-se estratégias que possam conduzir a melhorias efetivas de seu desempenho ambiental. Desenvolveu-se um modelo teórico, utilizando a estrutura de Sistemas Abertos e técnicas do pensamento sistêmico, identificando as variáveis que compõem as dinâmicas institucional e organizacional do setor. O modelo permitiu descrever, compreender e inferir sobre o comportamento futuro do sistema, além de estabelecer hipóteses para novos estudos. A partir do modelo, verificaram-se três diferentes estratégias empresariais na adoção dos padrões para certificação, sendo elas a "Adoção Simbólica", o "Mimetismo" e a "Adoção Efetiva". Concluiu-se que a opção por uma estratégia que conduza a mudanças efetivas no setor florestal requer o estabelecimento de uma visão compartilhada de sustentabilidade, que contribua para a consolidação de instituições e que oriente as respostas empresariais.

A opção por uma estratégia que conduza a mudanças efetivas no setor florestal requer o estabelecimento de uma visão compartilhada de sustentabilidade, que contribua para a consolidação de instituições e que oriente as respostas empresariais. Este estudo foi desenvolvido com o objetivo de identificar quais seriam os elementos que compõem a visão de sustentabilidade para o setor, a partir da opinião de diversos atores sociais que participam de seu campo organizacional. Aplicou-se a técnica de Mapeamento Conceitual, utilizando o programa CONCEPT SYSTEM versão 1.75 para processamento dos dados. As declarações geradas foram agrupadas em seis temas, que abrangeram elementos do manejo florestal ambientalmente adequado, socialmente justo e economicamente viável. Para compor a visão de sustentabilidade do setor florestal brasileiro, os participantes consideraram mais importantes os grupos de conceitos "Floresta e Sociedade" e "Conservação Ambiental". As respostas foram comparadas por segmento e considerou-se o nível de importância aplicado aos elementos da visão de sustentabilidade como um reflexo das regras, dos padrões e dos valores cognitivos dos representantes dos interesses econômicos, sociais e ambientais.

O objetivo deste trabalho foi avaliar qualitativamente os impactos ambientais provenientes do Pólo Moveleiro de Ubá. A identificação e descrição das atividades impactantes relacionadas ao referido pólo foram feitas com base em consulta a referências bibliográficas e no acompanhamento das atividades realizadas nas fábricas de móveis e de suas interferências nos meios físico, biótico e antrópico. O método de avaliação utilizado foi a Matriz de Interação, contendo as atividades impactantes em suas linhas e os fatores ambientais relevantes em suas colunas. Identificaram-se 28 atividades impactantes, divididas em quatro fases: pré-fabricação de móveis, fabricação de móveis, expedição e comercialização de móveis, e limpeza e conservação da fábrica. O meio antrópico foi o mais impactado, apresentando 79 relações de impacto, o que correspondeu a 49,07% do total. A principal conclusão é a de que tal método se mostrou eficiente para avaliação de impactos ambientais do empreendimento em questão, o que permite a este estudo ser um referencial no processo de licenciamento da indústria de móveis em Minas Gerais. Palavras-chave: impacto ambiental, indústria moveleira e pólo moveleiro de Ubá.

The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [(18)F]FEAU to monitor the long-term (up to 5 months) spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC) and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [(18)F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33-35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC-associated [(18)F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [(18)F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months) of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI.

Adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTLs) has been successfully used to treat patients with different types of cancer. However, the long-term spatial-temporal dynamics of the distribution of systemically infused CTLs remains largely unknown. Noninvasive imaging of adoptively transferred CTLs using molecular-genetic reporter imaging with positron emission tomography and computed tomography (PET-CT) represents an innovative approach to understanding the long-term migratory patterns and therapeutic potential of adoptively transferred T cells. Here we report the application of repetitive PET-CT imaging with [ 18 F]fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil ( 18 F-FEAU) in two nonhuman primates demonstrating that autologous polyclonal macaque T lymphocytes activated and transduced with a retroviral vector encoding for the sr39 mutant herpes simplex virus 1 thymidine kinase ( sr39HSV1-tk ) reporter gene can be detected after intravenous infusion in discrete lymphoid organs and in sites of inflammation. This study represents a proof of principle and supports the application of 18 F-FEAU PET-CT imaging for monitoring the distribution of intravenously administered sr39HSV1-tk gene-transduced CTLs in humans.