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1.
Public Health ; 227: 54-62, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38118243

ABSTRACT

OBJECTIVES: Addressing migrant population's sexual health needs is essential, given the high vulnerability of this population, especially during migratory trajectories and when accessing health care in destination countries. The aim of this scoping review is to identify and describe the structural and intermediary determinants and their dimensions, which negatively influence sexual healthcare access in migrant population in the world in the last 20 years. STUDY DESIGN: Scoping review. METHODS: The search strategy was carried out in the databases PubMed/MEDLINE, Web of Science, EMBASE, and CINAHL. The inclusion criteria were primary studies published in English or Spanish from 2000 to 2022, describing determinants or barriers to access to sexual health for international migrants, refugees, and asylum seekers. The construction of the results was based on the social determinants of health framework. RESULTS: A total of 44 studies were included. Thirteen categories that negatively affect access to sexual health in migrants were identified-structural determinants: language and communication barriers, religious and cultural values, VIH stigma and discrimination, irregular migration status, financial constraints, racism and discrimination, gender inequalities, and lack of knowledge and awareness about sexuality and sexual health; and intermediary determinants: financial health coverage, privacy and confidentiality, health system navigation; health system and facilities, and psychosocial factors. CONCLUSION: The most relevant dimensions identified as barriers to access to health services were "culture and societal values" and "health system". Identifying the determinants that affect migrants' access to sexual health is relevant for the formulation of public policies with sociocultural relevance and an intersectional and human rights approach.


Subject(s)
Refugees , Transients and Migrants , Humans , Health Services Accessibility , Health Services , Sexual Behavior
2.
ISME J ; 14(7): 1743-1754, 2020 07.
Article in English | MEDLINE | ID: mdl-32269378

ABSTRACT

Rhizopus microsporus is an early-diverging fungal species with importance in ecology, agriculture, food production, and public health. Pathogenic strains of R. microsporus harbor an intracellular bacterial symbiont, Mycetohabitans (formerly named Burkholderia). This vertically transmitted bacterial symbiont is responsible for the production of toxins crucial to the pathogenicity of Rhizopus and remarkably also for fungal reproduction. Here we show that R. microsporus can live not only in symbiosis with bacteria but also with two viral members of the genus Narnavirus. Our experiments revealed that both viruses replicated similarly in the growth conditions we tested. Viral copies were affected by the developmental stage of the fungus, the substrate, and the presence or absence of Mycetohabitans. Absolute quantification of narnaviruses in isolated asexual sporangiospores and sexual zygospores indicates their vertical transmission. By curing R. microsporus of its viral and bacterial symbionts and reinfecting bacteria to reestablish symbiosis, we demonstrate that these viruses affect fungal biology. Narnaviruses decrease asexual reproduction, but together with Mycetohabitans, are required for sexual reproductive success. This fungal-bacterial-viral system represents an outstanding model to investigate three-way microbial symbioses and their evolution.


Subject(s)
Burkholderia , Symbiosis , Rhizopus , Spores, Fungal
3.
Trop Anim Health Prod ; 51(6): 1295-1305, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31134554

ABSTRACT

We reviewed information on dairy cattle production systems in the tropics, the factors involved, and their influence on milk composition. Genetic factors had greater influence on milk production; specialized breeds produced more milk, and there was an inverse relation between the content of fat, protein, total solids, and the amount of milk produced. Season was related to the availability of forage, and the type of grazing system. Greater pasture area increased individual production, while a greater supply of feed concentrate did not increase milk production. The number of calvings positively affected milk production through the fifth calving, with subsequent declines in production. Milk production increased to a maximum and then declined as lactation progressed. Specialized systems had higher production and better hygienic milk quality; milking and container equipment are critical for maintaining milk sanitary quality. Factor interaction is highly complex, preventing the generation of specific recommendations and general principles applicable to the specific conditions for each system.


Subject(s)
Cattle/physiology , Dairying , Milk/standards , Animals , Cattle/classification , Cattle/genetics , Dairying/methods , Female , Seasons , Tropical Climate
4.
J Food Sci Technol ; 56(4): 1909-1917, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30996426

ABSTRACT

The objective was to evaluate the effect of pretreatments of CaCl2 and osmotic dehydration (OD) on oil absorption in plantain and cassava chips. Plantain and cassava slices (1 mm thickness and 35 mm diameter) were prepared. Pretreatment with and without 5% CaCl2 solution before applying OD with sucrose solutions at 30 and 45%, and NaCl at 3 and 6% in a product/solution ratio of 1:25, at 40 °C were employed. OD kinetics and diffusivity were estimated by Page's model and Fick's law, respectively. Best OD treatments for plantain chips were 45% sucrose with CaCl2 and 6% NaCl without CaCl2. However, for cassava chips, the best OD treatments were 45% sucrose without CaCl2 and 3% NaCl with CaCl2. Page's model predicted the OD experimental results with an R2 = 0.94-0.97. Effective diffusivity of water (EDW) and effective diffusivity of solids (EDS) for osmo-dehydrated cassava samples, with and without CaCl2, decreased as the concentration of the osmotic solutions was increased. However, in general, the inverse effect was obtained for plantain samples for EDW and EDS. Use of CaCl2 when applying OD reduced EDW and EDS in plantain and cassava chips. In general, it was observed that when increasing the concentration of the osmotic solution, oil absorption capacity decreased. Treatments that showed the lowest oil absorption were 45% sucrose OD in plantain chips pretreated with CaCl2 (11.49%) and fresh cassava chips with 45% sucrose OD (10.72%). The results and effectiveness will depend on food, process conditions and type of osmotic agent.

5.
J Food Sci Technol ; 55(10): 4244-4255, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30228423

ABSTRACT

The aim of this study was to optimize and characterize an extruded snack made with taro flour and mango pulp. A central experimental design composed of the following three variables was used: mango pulp proportion (MPP = 0-10 g/100 g) in taro flour, feed moisture content (FMC = 16-30 g/100 g) and extrusion temperature (zone 4 of extruder) (T = 80-150 °C) using a single-screw extruder with a compression screw ratio of 3:1. Increasing FMC values decreased the torque, pressure, specific mechanical energy (SME), expansion index (EI), water solubility index and pH values and increased the residence time, bulk density (BD), hardness and total colour difference. Increasing T values led to a decrease in the torque, pressure, BD and hardness values, while increasing MPP values only caused a significant increase in the hardness values and ß-carotene content and a decrease in the pressure value. The optimal extrusion conditions were T = 135.81 °C, FMC = 18.84 g/100 g and MPP = 7.97 g/100 g, with a desirability value of 0.772, to obtain a snack with EI = 1.52, BD = 0.66 g/cm3, hardness = 24.48 N, ß-carotene content = 99.1 µg/g and SME = 428.54 J/g. The mango pulp is an available and economical source of ß-carotene for the enrichment of extruded expanded taro snacks.

6.
J Food Sci Technol ; 55(1): 157-163, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29358806

ABSTRACT

This work aimed to evaluate the effect of enzymatic pretreatment on the color and texture of plantain (Musa ssp., group AAB) dried by airflow reversal drying. Plantain slices 1.0 cm thick were used. Pretreatment with two commercial enzymes, Pectinex Ultra SPL (Aspergillus aculeatus) and Pectinex 3XL (Aspergillus niger), was performed. Drying kinetics were determined with and without pretreatment at temperatures of 50, 65 and 80 °C using a fixed bed convective dryer. An air speed of 6 m/s, a bed height of 5 cm and either unidirectional flow or airflow reversal (every 15 min) were used for drying. Color and texture were analyzed, and consumer acceptance of the results of the best treatments was determined. Pretreatment with the enzyme A. niger and airflow reversal gave the best drying kinetics and showed the greatest reduction in drying time (59.0%) at 80 °C. The best hardness results were found at 80 °C with A. niger enzymatic pretreatment with both types of air flow. Brightness and hue angle showed that samples pretreated with enzymes and dried at 65 °C had a lighter yellow color compared to non-pretreated samples. Plantain samples enzymatically pretreated and dried at 65 and 80 °C were the most accepted by consumers. This kind of enzymatic pretreatment on plantain could allow the conservation of some physical properties and reduction of drying times relative to the current methodology.

7.
Leukemia ; 32(1): 83-91, 2018 01.
Article in English | MEDLINE | ID: mdl-28592889

ABSTRACT

In the phase 3 RESONATE study, ibrutinib demonstrated superior progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) compared with ofatumumab in relapsed/refractory CLL patients with high-risk prognostic factors. We report updated results from RESONATE in these traditionally chemotherapy resistant high-risk genomic subgroups at a median follow-up of 19 months. Mutations were detected by Foundation One Heme Panel. Baseline mutations in the ibrutinib arm included TP53 (51%), SF3B1 (31%), NOTCH1 (28%), ATM (19%) and BIRC3 (14%). Median PFS was not reached, with 74% of patients randomized to ibrutinib alive and progression-free at 24 months. The improved efficacy of ibrutinib vs ofatumumab continues in all prognostic subgroups including del17p and del11q. No significant difference within the ibrutinib arm was observed for PFS across most genomic subtypes, although a subset carrying both TP53 mutation and del17p had reduced PFS compared with patients with neither abnormality. Reduced PFS or OS was not evident in patients with only del17p. PFS was significantly better for ibrutinib-treated patients in second-line vs later lines of therapy. The robust clinical activity of ibrutinib continues to show ongoing efficacy and acceptable safety consistent with prior reports, independent of various known high-risk mutations.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Mutation/genetics , Adenine/analogs & derivatives , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/therapeutic use , Disease-Free Survival , Female , Follow-Up Studies , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Male , Middle Aged , Mutation/drug effects , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Piperidines , Prognosis , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Tumor Suppressor Protein p53/genetics
8.
Appl Radiat Isot ; 129: 28-34, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28802155

ABSTRACT

We present a methodology to obtain the energy distribution of the neutron flux of an experimental nuclear reactor, using multi-foil activation measurements and the Expectation Maximization unfolding algorithm, which is presented as an alternative to well known unfolding methods such as GRAVEL. Self-shielding flux corrections for energy bin groups were obtained using MCNP6 Monte Carlo simulations. We have made studies at the at the Dry Tube of RECH-1 obtaining fluxes of 1.5(4)×1013cm-2s-1 for the thermal neutron energy region, 1.9(5)×1012cm-2s-1 for the epithermal neutron energy region, and 4.3(11)×1011cm-2s-1 for the fast neutron energy region.

10.
Leukemia ; 31(6): 1348-1354, 2017 06.
Article in English | MEDLINE | ID: mdl-28115735

ABSTRACT

The clinical course of patients with recently diagnosed early stage chronic lymphocytic leukemia (CLL) is highly variable. We examined the relationship between CLL-cell birth rate and treatment-free survival (TFS) in 97 patients with recently diagnosed, Rai stage 0-II CLL in a blinded, prospective study, using in vivo 2H2O labeling. Birth rates ranged from 0.07 to 1.31% new cells per day. With median follow-up of 4.0 years, 33 subjects (34%) required treatment by NCI criteria. High-birth rate was observed in 44% of subjects and was significantly associated with shorter TFS, unmutated IGHV status and expression of ZAP70 and of CD38. In multivariable modeling considering age, gender, Rai stage, expression of ZAP70 or CD38, IGHV mutation status and FISH cytogenetics, only CLL-cell birth rate and IGHV mutation status met criteria for inclusion. Hazard ratios were 3.51 (P=0.002) for high-birth rate and 4.93 (P<0.001) for unmutated IGHV. The association between elevated birth rate and shorter TFS was observed in subjects with either mutated or unmutated IGHVs, and the use of both markers was a better predictor of TFS than either parameter alone. Thus, an increased CLL birth rate in early stage disease is a strong predictor of disease progression and earlier treatment.


Subject(s)
Biomarkers, Tumor/genetics , Cell Proliferation , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Mutation , Adult , Aged , Aged, 80 and over , Disease Progression , Female , Follow-Up Studies , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Male , Middle Aged , Neoplasm Staging , Prognosis , Prospective Studies , Survival Rate
11.
Acta Ortop Mex ; 30(2): 105-109, 2016.
Article in Spanish | MEDLINE | ID: mdl-27846360

ABSTRACT

BACKGROUND: Dislocation after total knee arthroplasty is a rare complication and a difficult problem to address. When the flexion gap is larger than the extension gap and the collateral ligaments are injured, instability and knee arthroplasty dislocation can occur. MATERIAL AND METHODS: We report the case of a patient presenting with a posterior dislocation of a posterior-stabilized prosthesis without trauma. Frank instability in varus stress test and a positive anterior drawer test with tibial internal rotation dismissed the conservative treatment. RESULTS: A constrained condylar prosthesis was used for the revision. He suffered a similar episode after a month, which demonstrated that the increase in the level of constraint was not enough to correct the severe asymmetric instability in flexion due to the damaged external structures. A rotating-hinge prosthesis was then implanted and the patient reported no additional episodes of instability. CONCLUSIONS: We made an exhaustive review of the literature, analyzed the possible causes that can lead to the tibiofemoral instability after a total knee arthroplasty and described some technical considerations.


La luxación tras la artroplastía de rodilla es una complicación poco frecuente y de difícil manejo. Una brecha en flexión demasiado grande asociada a una laxitud de los ligamentos colaterales puede llevar a la inestabilidad y a la luxación en flexión.


Subject(s)
Arthroplasty, Replacement, Knee , Joint Instability , Knee Prosthesis , Prosthesis Design , Humans , Knee Joint , Male , Reoperation
12.
Acta ortop. mex ; 30(2): 105-109, mar.-abr. 2016. tab, graf
Article in Spanish | LILACS | ID: biblio-837766

ABSTRACT

Resumen: Antecedentes: La luxación tras la artroplastía de rodilla es una complicación poco frecuente y de difícil manejo. Una brecha en flexión demasiado grande asociada a una laxitud de los ligamentos colaterales puede llevar a la inestabilidad y a la luxación en flexión. Material y métodos: Informamos del caso de un paciente que tuvo una luxación posterior de su prótesis de rodilla posteroestabilizada sin antecedente traumático. La inestabilidad franca al forzar el varo en flexión y un cajón anterior positivo que aumentaba en rotación interna condujeron a la revisión quirúrgica sin plantear un tratamiento conservador. Resultados: Se implantó una prótesis condilar constreñida tras lo cual sufrió un nuevo episodio de las mismas características un mes después, que puso de manifiesto que el nivel de constricción no fue suficiente para la inestabilidad severa en flexión asimétrica por insuficiencia de las estructuras externas. Luego de implantarle una prótesis tipo bisagra rotatoria, no ha tenido nuevos episodios de inestabilidad. Conclusiones: A través de un repaso exhaustivo de la bibliografía, se describen los posibles factores que pueden conducir a la inestabilidad tibiofemoral tras la artroplastía total de rodilla, así como las consideraciones técnicas para su manejo.


Abstract: Background: Dislocation after total knee arthroplasty is a rare complication and a difficult problem to address. When the flexion gap is larger than the extension gap and the collateral ligaments are injured, instability and knee arthroplasty dislocation can occur. Material and methods: We report the case of a patient presenting with a posterior dislocation of a posterior-stabilized prosthesis without trauma. Frank instability in varus stress test and a positive anterior drawer test with tibial internal rotation dismissed the conservative treatment. Results: A constrained condylar prosthesis was used for the revision. He suffered a similar episode after a month, which demonstrated that the increase in the level of constraint was not enough to correct the severe asymmetric instability in flexion due to the damaged external structures. A rotating-hinge prosthesis was then implanted and the patient reported no additional episodes of instability. Conclusions: We made an exhaustive review of the literature, analyzed the possible causes that can lead to the tibiofemoral instability after a total knee arthroplasty and described some technical considerations.


Subject(s)
Humans , Male , Prosthesis Design , Arthroplasty, Replacement, Knee , Joint Instability , Knee Prosthesis , Reoperation , Knee Joint
13.
Leukemia ; 30(1): 74-85, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26220042

ABSTRACT

The degree of chronic lymphocytic leukemia (CLL) B-cell antigen receptor (BCR) binding to myosin-exposed apoptotic cells (MEACs) correlates with worse patient outcomes, suggesting a link to disease activity. Therefore, we studied MEAC formation and the effects of MEAC binding on CLL cells. In cell line studies, both intrinsic (spontaneous or camptothecin-induced) and extrinsic (FasL- or anti-Fas-induced) apoptosis created a high percent of MEACs over time in a process associated with caspase-3 activation, leading to cytoplasmic myosin cleavage and trafficking to cell membranes. The involvement of common apoptosis pathways suggests that most cells can produce MEACs and indeed CLL cells themselves form MEACs. Consistent with the idea that MEAC formation may be a signal to remove dying cells, we found that natural IgM antibodies bind to MEACs. Functionally, co-culture of MEACs with CLL cells, regardless of immunoglobulin heavy-chain variable region gene mutation status, improved leukemic cell viability. Based on inhibitor studies, this improved viability involved BCR signaling molecules. These results support the hypothesis that stimulation of CLL cells with antigen, such as those on MEACs, promotes CLL cell viability, which in turn could lead to progression to worse disease.


Subject(s)
Apoptosis , Caspase 3/metabolism , Cytoplasm/enzymology , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Myosins/physiology , Cell Survival , Cells, Cultured , Enzyme Activation , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/enzymology , Receptors, Antigen, B-Cell/physiology , Signal Transduction
14.
Oecologia ; 180(1): 193-203, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26376660

ABSTRACT

Predators have far-reaching effects on communities by triggering top-down trophic cascades that influence ecosystem functioning. Omnivory and intraguild interactions between predators give rise to reticulate food webs and may either strengthen or dampen trophic cascades depending on context. Disentangling the effects of multiple predator species is therefore crucial for predicting the influence of predators on community structure. We focused on ants as dominant generalist predators in arthropod communities and set up a differential ant exclusion from canopies to examine its effects on assemblage species composition and densities of five arthropod groups (psocopterans, aphids, spiders, heteropterans and beetles). We coupled a glue band with tubes allowing only the ant Lasius grandis to reach the canopies to isolate its effect from the rest of crawling predators (ants, earwigs) and compared it against a full exclusion and a control. L. grandis alone had widespread effects on assemblage species composition, with contrasting species-specific responses within groups, where some species affected by L. grandis presence were not further affected by the presence of the whole crawling predator assemblage, and vice versa. Overall, L. grandis caused two- to threefold decreases of generalist predators and a threefold increase of aphids. However, it lacked further top-down effects on primary consumers, which only emerged when all crawling predators were present. This differential exclusion demonstrates the distinctive and widespread intraguild effects on community structure of a single ant species that contrast with the top-down effects exerted by the whole crawling predator assemblage.


Subject(s)
Ants , Arthropods , Feeding Behavior , Food Chain , Plant Leaves , Predatory Behavior , Animals , Aphids , Biodiversity , Coleoptera , Population Dynamics , Spiders
15.
Neuroscience ; 280: 156-70, 2014 Nov 07.
Article in English | MEDLINE | ID: mdl-25241069

ABSTRACT

Experimental evidence has revealed the role of mitochondria in various aspects of neuronal physiology. Mitochondrial failure results in alterations that underlie the pathogeneses of many neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, Huntington's disease (HD) and amyotrophic lateral sclerosis. The mitochondrial toxin 3-nitropropionic acid (3-NP) has been used to model failure; for example, systemic administration of 3-NP imitates the striatal degeneration that is exhibited in the postmortem tissue of patients afflicted with HD. We have demonstrated that low, sub-chronic doses of 3-NP are sufficient to initiate the damage to striatal neurons that is associated with changes in neurotrophin expression levels. However, the mechanisms underlying the alterations in neuronal activity and neurotransmission due to 3-NP-induced mitochondrial dysfunction remain to be elucidated. In this paper, we focus on how corticostriatal transmission and its modulation by neurotrophins are altered in vivo after 5 days of mitochondrial inhibition with 3-NP. Recordings of population spikes and a paired pulse (PP) stimulation protocol were used to document changes in corticostriatal synapses in 3-NP-treated brain slices. The corticostriatal synapses were modulated by neurotrophins but displayed differential amplitude increases in the presence of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotrophin-4/5 (NT-4/5) under control conditions. Neurotrophin-mediated synaptic modulation was decreased in slices from 3-NP-treated mice. The protein and mRNA levels of neurotrophins and their receptors were also modified in the 3-NP-treated tissue. Neuronal structural evaluation demonstrated that synaptic length and density were reduced in the 3-NP-treated mice, which partially explained the changes in the amplitudes of the synaptic field responses. Our results demonstrate that corticostriatal synapses are differentially modulated by neurotrophins and that this modulation is altered by mitochondrial failure. Mitochondrial dysfunction also affects neurotransmitter release in corticostriatal synapses, neurotrophin availability, dendritic arborization and the lengths of the striatal medium spiny neurons (MSNs).


Subject(s)
Cerebral Cortex/physiology , Corpus Striatum/physiology , Mitochondria/physiology , Nerve Growth Factors/metabolism , Synapses/physiology , Synaptic Transmission/physiology , Animals , Brain-Derived Neurotrophic Factor/metabolism , Cerebral Cortex/drug effects , Cerebral Cortex/pathology , Corpus Striatum/drug effects , Corpus Striatum/pathology , Glutamic Acid/metabolism , Male , Mice, Inbred C57BL , Mitochondria/drug effects , Mitochondrial Diseases , Neural Pathways/drug effects , Neural Pathways/pathology , Neural Pathways/physiology , Neurotrophin 3/metabolism , Nitro Compounds/toxicity , Propionates/toxicity , Random Allocation , Receptors, Nerve Growth Factor/metabolism , Synapses/drug effects , Synapses/pathology , Tissue Culture Techniques
16.
Oecologia ; 173(1): 239-48, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23361153

ABSTRACT

Ants and spiders are ubiquitous generalist predators that exert top-down control on herbivore populations. Research shows that intraguild interactions between ants and spiders can negatively affect spider populations, but there is a lack of long-term research documenting the strength of such interactions and the potentially different effects of ants on the diverse array of species in a spider assemblage. Similarly, the suitability of family-level surrogates for finding patterns revealed by species-level data (taxonomic sufficiency) has almost never been tested in spider assemblages. We present a long-term study in which we tested the impact of ants on the spider assemblage of a Mediterranean citrus grove by performing sequential 1-year experimental exclusions on tree canopies for 8 years. We found that ants had a widespread influence on the spider assemblage, although the effect was only evident in the last 5 years of the study. During those years, ants negatively affected many spiders, and effects were especially strong for sedentary spiders. Analyses at the family level also detected assemblage differences between treatments, but they concealed the different responses to ant exclusion shown by some related spider species. Our findings show that the effects of experimental manipulations in ecology can vary greatly over time and highlight the need for long-term studies to document species interactions.


Subject(s)
Ants/physiology , Citrus , Spiders/physiology , Animals , Food Chain , Mediterranean Region , Population Density , Population Dynamics , Predatory Behavior , Spiders/classification , Time Factors
17.
Math Comput Model Dyn Syst ; 17(2): 183-203, 2011 Jan 12.
Article in English | MEDLINE | ID: mdl-21673826

ABSTRACT

We present a dynamical model incorporating both physiological and psychological factors that predicts changes in body mass and composition during the course of a behavioral intervention for weight loss. The model consists of a three-compartment energy balance integrated with a mechanistic psychological model inspired by the Theory of Planned Behavior (TPB). The latter describes how important variables in a behavioural intervention can influence healthy eating habits and increased physical activity over time. The novelty of the approach lies in representing the behavioural intervention as a dynamical system, and the integration of the psychological and energy balance models. Two simulation scenarios are presented that illustrate how the model can improve the understanding of how changes in intervention components and participant differences affect outcomes. Consequently, the model can be used to inform behavioural scientists in the design of optimised interventions for weight loss and body composition change.

19.
Leukemia ; 22(9): 1755-66, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18596745

ABSTRACT

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although some patients can be cured by current therapies, novel agents are needed to further improve outcomes. We hypothesized that Src tyrosine kinase inhibition by dasatinib may have antilymphoma effects. Here, we demonstrate that dasatinib inhibits cell growth through G(1)-S blockage in five of seven DLBCL cell lines at clinically achievable concentrations. Compared to resting B cells, DLBCL has increased tyrosine phosphorylation activities. As expected, dasatinib inhibits phosphorylation of several Src family kinase members. However, this inhibition occurs in all cell lines regardless of their proliferative response to the drug. In contrast, the activity of two downstream signaling molecules, Syk and phospholipase Cgamma2 (PLCgamma2), are well correlated with cell line sensitivity to dasatinib, suggesting that these molecules are crucial in mediating the proliferation of activated lymphoma cells. Furthermore, dasatinib inhibits B-cell receptor signaling in primary lymphoma cells. Together, our findings not only show dasatinib as a potentially useful therapy for DLBCL but also provide insights into the pathogenesis of the lymphoma. The results further suggest the possibility of using Syk and PLCgamma2 as biomarkers to predict dasatinib therapeutic response in prospective clinical trials.


Subject(s)
Cell Proliferation/drug effects , Drug Resistance, Neoplasm , Lymphoma, Large B-Cell, Diffuse/drug therapy , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyrimidines/pharmacology , Thiazoles/pharmacology , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Dasatinib , Humans , Interphase/drug effects , Intracellular Signaling Peptides and Proteins/metabolism , Phospholipase C gamma/metabolism , Protein Kinase Inhibitors/pharmacology , Protein-Tyrosine Kinases/metabolism , Receptors, Antigen, B-Cell/metabolism , Syk Kinase , src-Family Kinases/antagonists & inhibitors
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