Partnering with carryouts: implementation of a food environment intervention targeting youth obesity.

Youth obesity is a major public health problem in the United States, especially among urban-based, minority youth. The B'More Healthy Communities for Kids (BHCK) trial worked at multiple levels of the food environment, including carryouts, to increase access to and demand for healthy, affordable foods. The objective of this article is to describe the development and implementation of BHCK's carryout intervention. Process evaluation was conducted to assess intervention reach (number of interactions with youth and adults either in person or on social media), dose delivered (number of food samples and promotional materials distributed, social media posts and meetings with owners) and fidelity (availability of promoted items). Overall, the carryout intervention showed moderate to optimal reach, moderate to optimal dose delivered and moderate to optimal fidelity. These findings demonstrate a successfully implemented carryout intervention in a low-income urban setting. Lessons learned about new methods for engaging the community and increasing demand for healthy food can be used to inform future studies and programs to improve the food environment.

Implementation of B'More Healthy Communities for Kids: process evaluation of a multi-level, multi-component obesity prevention intervention.

B'More Healthy Communities for Kids was a multi-level, multi-component obesity prevention intervention to improve access, demand and consumption of healthier foods and beverages in 28 low-income neighborhoods in Baltimore City, MD. Process evaluation assesses the implementation of an intervention and monitor progress. To the best of our knowledge, little detailed process data from multi-level obesity prevention trials have been published. Implementation of each intervention component (wholesaler, recreation center, carryout restaurant, corner store, policy and social media/text messaging) was classified as high, medium or low according to set standards. The wholesaler component achieved high implementation for reach, dose delivered and fidelity. Recreation center and carryout restaurant components achieved medium reach, dose delivered and fidelity. Corner stores achieved medium reach and dose delivered and high fidelity. The policy component achieved high reach and medium dose delivered and fidelity. Social media/text messaging achieved medium reach and high dose delivered and fidelity. Overall, study reach and dose delivered achieved a high implementation level, whereas fidelity achieved a medium level. Varying levels of implementation may have balanced the performance of an intervention component for each process evaluation construct. This detailed process evaluation of the B'More Healthy Communities for Kids allowed the assessment of implementation successes, failures and challenges of each intervention component.

Characterization of monocyte-derived dendritic cells from patients with active and treated paracoccidioidomycosis.

Cellular immune responses are a significant defence mechanism in human paracoccidioidomycosis (PCM), an endemic mycosis in Latin America; however, little is known about the role of dendritic cells (DCs) in human PCM. We investigated monocyte-derived DCs from patients with treated (TP) and active PCM (AP) compared with healthy non-PCM donors (CO). DCs from the TP group showed higher expression of HLA-DR, CD86 and DC-SIGN compared with CO, whereas AP showed similar expression to CO. Production of IL-10 was downregulated by TNF-α in all groups and lower levels were observed in untreated DCs from AP compared with CO. Conversely, IL-12p40 was significantly upregulated in the DCs of the TP group. TNF-α-activated DCs from the CO group produced significantly lower levels of IL-12p40 when differentiated from magnetic-sorted monocytes (MACS) compared with adhered monocyte-derived DCs. This comparison in the TP group revealed similar levels of IL-12p40, suggesting a T cell-independent increase in the production of IL-12p40. Higher expression of surface molecules with increased IL-12p40 may indicate a better activation of DCs after the treatment of PCM. Our findings suggest that DCs may be crucial in the protective response to Paracoccidioides brasiliensis and that in vitro-generated DCs might be useful in enhancing antifungal immunity, especially during active PCM.

Changes in Myocardial Metabolism Preceding Sudden Cardiac Death.

Heart disease is widely recognized as a major cause of death worldwide and is the leading cause of mortality in the United States. Centuries of research have focused on defining mechanistic alterations that drive cardiac pathogenesis, yet sudden cardiac death (SCD) remains a common unpredictable event that claims lives in every age group. The heart supplies blood to all tissues while maintaining a constant electrical and hormonal feedback communication with other parts of the body. As such, recent research has focused on understanding how myocardial electrical and structural properties are altered by cardiac metabolism and the various signaling pathways associated with it. The importance of cardiac metabolism in maintaining myocardial function, or lack thereof, is exemplified by shifts in cardiac substrate preference during normal development and various pathological conditions. For instance, a shift from fatty acid (FA) oxidation to oxygen-sparing glycolytic energy production has been reported in many types of cardiac pathologies. Compounded by an uncoupling of glycolysis and glucose oxidation this leads to accumulation of undesirable levels of intermediate metabolites. The resulting accumulation of intermediary metabolites impacts cardiac mitochondrial function and dysregulates metabolic pathways through several mechanisms, which will be reviewed here. Importantly, reversal of metabolic maladaptation has been shown to elicit positive therapeutic effects, limiting cardiac remodeling and at least partially restoring contractile efficiency. Therein, the underlying metabolic adaptations in an array of pathological conditions as well as recently discovered downstream effects of various substrate utilization provide guidance for future therapeutic targeting. Here, we will review recent data on alterations in substrate utilization in the healthy and diseased heart, metabolic pathways governing cardiac pathogenesis, mitochondrial function in the diseased myocardium, and potential metabolism-based therapeutic interventions in disease.

yote Alkaloids: Identification in the Mexican ictus Pelecyphora aselliformis Ehrenberg.

Hordenine, anhalidine, pellotine, 3-demethyltrichocereine, mescaline, dimethoxy-beta-phenethylamine, and the N-monomethyl derivatives of mescaline d 3,4-dimethoxy-beta-phenethylamine have been isolated or identified, or both, in caloid extracts of a Mexican "peyote" cactus, Pelecyphora aselliformis tenberg. This is the first report of the occurrence of some of these alkaloids, including mescaline, in a North American cactus other than Lophophora.

Subsite substrate specificity of midgut insect chymotrypsins.

Insect chymotrypsins are distinctively sensitive to plant protein inhibitors, suggesting that they differ in subsite architecture and hence in substrate specificities. Purified digestive chymotrypsins from insects of three different orders were assayed with internally quenched fluorescent oligopeptides with three different amino acids at P1 (Tyr, Phe, and Leu) and 13 amino acid replacements in positions P1', P2, and P3. The binding energy (DeltaG(s), calculated from K(m) values) and the activation energy (DeltaG(T)++, determined from k(cat)/K(m) values) were calculated. The hydrophobicities of each subsite were calculated from the efficiency of hydrolysis of the different amino acid replacements at that subsite. The results showed that except for S1, the other subsites (S2, S3, and S1') vary among chymotrypsins. This result contrasts with insect trypsin data that revealed a trend along evolution, putatively associated with resistance to plant inhibitors. In spite of those differences, the data suggested that in lepidopteran chymotrypsins S2 and S1' bind the substrate ground state, whereas only S1' binds the transition state, supporting aspects of the present accepted mechanism of catalysis.

Effects of health at every size® interventions on health-related outcomes of people with overweight and obesity: a systematic review.

CONTEXT: The growing use of interventions based on the Health at Every Size® (HAES®) in obesity management. OBJECTIVE: This study aimed to summarize the health-related effects of HAES®-based interventions on people with overweight and obesity. DATA SOURCES: MEDLINE (via PubMed), EMBASE, Cochrane Library, LILACS, Google Scholar, OpenGrey and Grey Literature Report. STUDY SELECTION: A systematic review of studies published until January 2017 reporting on HAES®-based randomized and non-randomized controlled trials in people with overweight and/or obesity. DATA EXTRACTION: Fourteen papers met the inclusion criteria. The assessed studies included the following tests: blood profile, blood pressure, anthropometry, eating behaviour, energy intake, diet quality, psychological and qualitative evaluations. RESULTS: The HAES® interventions benefited both the psychological and physical activity outcomes, besides promoting behavioural and qualitative changes in eating habits. On the other hand, the results regarding cardiovascular responses, body-image perception and total energy intake were inconsistent. CONCLUSIONS: Despite improving the cardiovascular status, eating behaviours, quality of life and psychological well-being in participants, other large long-term clinical trials should be performed to establish the effectiveness of HAES®-based interventions in improving health for people with overweight and obesity. PROSPERO registration 2017: CRD42017054857.

Polymorphisms on IFNG, IL12B and IL12RB1 genes and paracoccidioidomycosis in the Brazilian population.

Paracoccidioidomycosis (PCM) is a systemic chronic mycosis, endemic in Latin America, especially Brazil, and is the eighth leading cause of death among chronic and recurrent infectious diseases. PCM infection is characterized by the presence of Th1 immune response; the acute form, by a mixed Th2/Th9, while the chronic form is characterized by Th17/Th22 profiles. The occurrence and severity of human PCM may also be associated with genetic factors such as single nucleotide polymorphisms (SNP) on cytokines encoding genes. We investigated the association between these polymorphisms and the different clinical forms of PCM. We included 156 patients with PCM (40 with the acute form, 99 with the chronic multifocal and 17 with the chronic unifocal form) and assayed their DNA samples for IFNG +874 T/A SNP by PCR-ARMS (Amplification Refractory Mutational System), IL12B +1188 A/C SNP on 3' UTR and IL12RB1 641 A/G SNP on exon 7 by PCR-RFLP (Restriction Fragment Length Polymorphism). We found similar genotypic and allelic frequencies of the investigated SNPs among the clinical forms of PCM. Considering male patients, the IL12RB1 641 AA genotype was more frequent in the chronic multifocal form while heterozygosis was in the chronic unifocal form of PCM (p=0.048). Although our data suggest that the AA genotype (IL12RB1) may be associated with the more disseminated chronic disease, more patients of the chronic unifocal PCM group need to be analyzed as well as the secretion patterns of IFN-γ combined with the IL-12Rß1 expression for a better comprehension of this association.

Prevention indicators for evaluating the progress of national AIDS programmes.

PIP: Major interventions to reduce HIV transmission involve increasing knowledge about preventing HIV transmission for sustained behavioral changes; and enhancing the control of sexually transmitted diseases (STD), which increase the probability of HIV transmission. Activities have also been developed to prevent the transmission of HIV by blood, donor selection, and more rational use of transfusions. Behavioral changes among injecting drug users have also been promoted. Recommendations are made for the evaluation of AIDS programs, focusing on prevention of sexual transmission of HIV, and outlining the approach developed by the Global Program on AIDS (GPA; Geneva, Switzerland) for use by national programs. Based on the feasibility, accuracy, reliability and validity of the quantitative assessment of programs, 10 indicators of progress and outcomes of prevention activities have been developed by GPA. These include indicators of population knowledge regarding preventive practices, reported sexual behavior and use of condoms in the general population, STD service evaluation, and indicators of program impact. The latter are measured through the reported STD incidence in the general male population, and syphilis and HIV prevalence in women. The four methods are proposed for measuring the 10 core prevention indicators (PI). Five PIs are measured during a population survey: reported knowledge of preventive practices (PI-1), condom availability at peripheral level (PI-3), reported frequency of nonregular sexual partners (PI-4), reported condom use during nonregular sexual encounters (PI-5), and reported STD incidence among men (PI-9). Condom availability at central level (PI-2) is assessed through key-informant interviews with major distributors. Structured health facility surveys allow assessment of the appropriateness of STD case management (PI-6 and PI-7). A serosurvey among antenatal clinic attenders aged 15-24 years allows the measurement of HIV and syphilis seroprevalence in that population (PI-8 and PI-10). GPA recommends that such surveys be repeated after a period of 1 to several years.^ieng

Differences in the inhibition of translation by cisplatin, transplatin, and certain related compounds.

The non-therapeutic cisplatin congeners transplatin and chloroethylenetriamine platinum (dien) inhibited translation to a similar extent as cisplatin did. The IC50 values were: cisplatin 23 microM, transplatin 54 microM, and dien 117 microM. Unlike certain heavy metal inhibitors of translation, the effect of neither cisplatin nor the congeners was reversed by 3':5'-cyclic adenosine monophosphate (cAMP). This suggests that the effect of these platinum compounds does not occur by the heavy metal mechanism. Polyribosomes and ribosomal subunits formed in transplatin-inhibited reactions differed from those in reactions inhibited by cisplatin. Specifically, large polyribosomes and complete 80S ribosomal subunits accumulated in the presence of transplatin. This indicates that while cisplatin slowed initiation of peptide synthesis, the trans-isomer slowed elongation. Substantive differences were not found between cisplatin and the monofunctional compound dien. This congener increased the non-peptidyl disintegrations per minute in the acid precipitates of assays containing [35S]methionine. The high background indicated that an interaction between the label and a precipitable component of the system was induced by dien. However, consumption of methionine by this interaction did not appear to be the cause of the inhibition. Although there may be differences in the mechanisms of the effects, the finding that the non-therapeutic congeners inhibit translation at similar concentrations as cisplatin suggests that this inhibition is not responsible for the anticancer effect. On the other hand, the possibility that decreased translation could play an important role in the toxicity of these compounds in certain quiescent cells cannot be ruled out.

Ascorbic acid: an endogenous inhibitor of isolated Na+,K+-ATPase.

During attempts to isolate and identify an endogenous ligand for the glycoside binding sites on Na+,K+-ATPase, bovine adrenal glands were found to contain a potent inhibitor of isolated Na+,K+-ATPase. The inhibitory principle was extracted from adrenal cortex, following homogenization in NaHCO3 solution and separation on a Sephadex G-10 column. The active principle was recovered from a fraction which eluted from the column after the 3H2O peak. The extract inhibited isolated Na+,K+-ATPase and the specific [3H]ouabain binding reaction. Sensitivity of the enzyme to the inhibitory action of the extract was species and tissue dependent; however, the pattern and the magnitude of the sensitivity were different from those of the digitalis glycosides. Moreover, the inhibitory principle failed to inhibit sodium pump activity, estimated from ouabain inhibitable 86Rb+ uptake by guinea pig brain slices. The activity of the extract to inhibit isolated Na+,K+-ATPase was stable under acidic condition but was lost rapidly at neutral pH, and could be eliminated by EDTA. In an acidic medium, the inhibitory principle had an absorption maximum at 244 nm which shifted to 264 nm and decayed rapidly at neutral pH. By using mass spectrometry, the principle was identified to be ascorbic acid, which has been shown previously to inhibit isolated Na+,K+-ATPase under appropriate conditions. Because ascorbic acid was incapable of inhibiting the sodium pump in intact cells, this inhibitor of the isolated enzyme does not appear to be the endogenous ligand which regulates sodium pump activity in vivo.

Hypnosis effect on carbon dioxide chemosensitivity.

Hypnosis is an induced state of heightened suggestibility during which certain physiologic variables can be altered. To investigate if carbon dioxide (CO2) chemosensitivity could be blunted during this suggestible state, we measured hypercapnic ventilatory response (HCVR, delta VE/delta PaCO2), oxygen consumption (VO2), breathing pattern (VT and f), inspiratory flow rate (VT/Ti), and inspiratory timing (Ti/Ttot) in 20 healthy subjects. Mouth occlusion pressures (P0.1) were measured in the last nine subjects. Resting oxygen consumption and minute ventilation were measured during awake and hypnotic control states. The HCVR was measured spontaneously and with the suggestion to maintain normal ventilation during both awake and hypnotic conditions. It was found that without a change in metabolism, ventilatory responses to CO2 could be blunted both voluntarily, and to a greater degree, with hypnotic suggestion. These findings may have important implications in clinical settings in which patients suffer from marked dyspnea secondary to increased ventilatory chemosensitivity.

Bronchiolitis obliterans caused by Legionella pneumophila.

A diabetic patient presented with symptoms and laboratory findings compatible with atypical pneumonia. Despite appropriate antibiotic therapy, his dyspnea, arterial oxygenation, and chest roentgenographic findings worsened. Because the patient had a history of homosexual contact, an open lung biopsy was obtained to morphologically define the tissue reaction and to search for a specific etiology. Histologic examination showed bronchiolitis obliterans but did not demonstrate a cause. Legionnaires' disease was subsequently diagnosed on the basis of a fourfold rise in indirect fluorescent antibody titer. This case report demonstrates that Legionella pneumophila may induce lung injury with bronchiolitis obliterans. Such patients may benefit from corticosteroid treatment.

The global HIV pandemic.

The paper reviews the distribution, transmission patterns, and likely impacts of the HIV pandemic at the beginning of 1993. As of early 1993, a cumulative total of 611,589 cases of AIDS were reported to the World Health Organization (WHO); however, because of less than complete diagnosis and reporting, the WHO estimates that a total of 2.5 million cases of AIDS had actually occurred. As of early 1993, the WHO estimates that there have been approximately 13 million infections, of which about 1 million have been in children. By the year 2000 the WHO predicts that there will be 30-40 million cumulative infections in the world, of which 90% will be in developing countries and almost half will be among women. The epidemic of HIV infection in the decade of the 1980s will result in an epidemic of AIDS in the 1990s, which will place great social and economic strains on many countries, particularly those in many areas of the developing world.