AIM： To determine the prevalence of celiac disease in a group of volunteer blood donors at a blood bank in the city of Curitiba, Brazil through detection of the serum marker immunoglobulin A （IgA） antitransglutamin...AIM： To determine the prevalence of celiac disease in a group of volunteer blood donors at a blood bank in the city of Curitiba, Brazil through detection of the serum marker immunoglobulin A （IgA） antitransglutaminase antibody. METHODS： Blood samples collected from 2086 healthy subjects at the Paraná State Center for Hematology and Hemotherapy in Curitiba were submitted to ELISA testing for the IgA antitransglutaminase antibody. Positive samples received IgA antiendomysium antibody test through indirect immunofluorescence using human umbilical cord as substrate. Subsequently, patients who were positive on both tests underwent small bowel （distal duodenum） biopsy. RESULTS： Six subjects, four males and two females, tested positive for the two serum markers. Five of the six were submitted to intestinal biopsy （one declined the procedure）. Biopsy results revealed changes in the distal duodenum mucosa （three classified as Marsh mb lesions and two as Marsh Ⅱ lesions）. Most donors diagnosed having celiac disease presented multiple symptoms （gastrointestinal tract complaints）. One donor reported having a family history of celiac disease （in a niece）. CONCLUSION： Among apparently healthy blood donors,the prevalence of biopsy-confirmed celiac disease was approximately 1：417, similar to that seen in European countries.展开更多
Regulatory T cells （Tregs） are a specialized subpopulation of T cells that control the immune response and thereby maintain immune system homeostasis and tolerance to self-antigens. Many subsets of CD4＋ Tregs have ...Regulatory T cells （Tregs） are a specialized subpopulation of T cells that control the immune response and thereby maintain immune system homeostasis and tolerance to self-antigens. Many subsets of CD4＋ Tregs have been identified, including Foxp3~, Trl, Th3, and Foxp3neg iT（R）35 cells. In this study, we identified a new subset of CD4＋VEGFR1high Tregs that have immunosuppressive capacity. CD4＋VEGFRlhigh T cells, which constitute approximately 1.0% of CD4＋ T cells, are hyporesponsive to T-cell antigen receptor stimulation. Surface marker and FoxP3 expression analysis revealed that CD4＋VEGFR1high T cells are distinct from known Tregs. CD4＋VEGFR1high T cells suppressed the proliferation of CD4＋CD25- T cell as efficiently as CD4＋CD25high natural Tregs in a contact-independent manner. Furthermore, adoptive transfer of CD4＋VEGFR1＋ T cells from wild type to RAG-2-deficient C57BL/6 mice inhibited effector T-cell-mediated inflammatory bowel disease. Thus, we report CD4＋ VEGFR1high T cells as a novel subset of Tregs that regulate the inflammatory response in the intestinal tract.展开更多
Brazil is one of the highest endemic countries for Zoonotic Visceral Leishmaniasis:according to the Brazilian Ministry of Health,the annual number of new human cases and deaths due to this disease has been increasing ...Brazil is one of the highest endemic countries for Zoonotic Visceral Leishmaniasis:according to the Brazilian Ministry of Health,the annual number of new human cases and deaths due to this disease has been increasing for the last 20 years.In addition,regarding the Americas,the specific relationship between canine and human for Visceral Leishmaniasis dynamics is still not well understood.In this work we propose a new model for Zoonotic Visceral Leishmaniasis,based on the models previously published by Burattini et al.(1998)and Ribas et al.(2013).Herein,we modeled the disease dynamics using a modified set of differential equations from those two authors,considering the same assumptions(inclusion of human,dog and sandfly populations,all constants over time).From this set of equations we were able to calculate the basic reproduction number R 0 and to analyze the stability and sensitivity of the system to the parameters variability.As main result,when the stability of the system is reached,the normalized reporting human cases rate is estimated in 9.12E-08/day.This estimation is very close to the 2015 report from Araçatuba city,5.69E-08/day.We also observed from stability and sensitivity analysis that the activity of sandfly population is critical to introduction and maintenance of Zoonotic Visceral Leishmaniasis in the population.In addition,the importance of dog as source of infection concentrates on latent dog,since it does not show clinical symptoms and signs and,therefore,has a great contribution to disease dissemination.As conclusion,considering the presently ethical issues regarding to elimination of positive dog in Brazil and the highly sensitivity of disease dynamics on sandfly population,we recommend that the sandfly population control should be prioritized.展开更多
AIM: To simulate a hypothetical increase of 50% in the number of pancreas-kidney (PK) transplantations using less-than-ideal donors by a mathematical model. METHODS: We projected the size of the waiting list by taking...AIM: To simulate a hypothetical increase of 50% in the number of pancreas-kidney (PK) transplantations using less-than-ideal donors by a mathematical model. METHODS: We projected the size of the waiting list by taking into account the incidence of new patients per year, the number of PK transplantations carried out in the year and the number of patients who died on the waiting list or were removed from the list for other reasons. These variables were treated using a model developed elsewhere. RESULTS: We found that the waiting list demand will meet the number of PK transplantation by the year 2022. CONCLUSION: In future years, it is perfectly possible to minimize the waiting list time for pancreas transplantation through expansion of the donor pool using less-than-ideal donors.展开更多
AIM: To assess the distribution of proteins coded by genes reported as relevant for the molecular classification of hepatocellular carcinoma (HCC).METHODS: In this retrospective cross-sectional study, the following cl...AIM: To assess the distribution of proteins coded by genes reported as relevant for the molecular classification of hepatocellular carcinoma (HCC).METHODS: In this retrospective cross-sectional study, the following clinicopathological data were analyzed in 80 autopsied HCC patients: sex, age, ethnicity, alcohol intake, infection with hepatitis B and/or C virus, infection with human immunodeficiency virus, prior treatment, basic and immediate causes of death, liver weight, presence of cirrhosis, number and size of nodules, gross pattern, histological grade and variants, architectural pattern, invasion of large veins, and presence and location of extrahepatic metastases. The protein products of genes known to be involved in molecular pathogenesis of HCC, including epidermal growth factor receptor (EGFR), MET, keratin 19 (K19), vimentin, beta-catenin, mechanistic target of rapamycin (mTOR), extracellular signaling-related kinase (ERK)1, ERK2, Ki67, cyclin D1, caspase 3 and p53, were detected by immunohistochemistry on tissue microarrays. The expression levels were scored and statistically assessed for correlation with HCC parameters.RESULTS: Infection with hepatitis C virus was identified in 49% of the 80 autopsy patients, cirrhosis in 90%, advanced tumors in 95%, and extrahepatic metastases in 38%. Expression of K19, p53 and ERK1 correlated to high-grade lesions. Expression of ERK1, nuclear beta-catenin, cyclin D1 and ERK2 correlated to higher rates of cell proliferation as determined by Ki67. Expression of MET, EGFR (> 0) and caspase 3 correlated with lower histological grades. Expression of EGFR correlated to that of caspase 3, and overexpression of EGFR (≥ 200/300) was observed in low-grade tumors more frequently (grades 1 and 2: 67% vs grade 3: 27% and grade 4: 30%). Expression of ERK1 was associated with that of K19 and vimentin, whereas expression of ERK2 was associated with that of cyclin D1, MET and membrane beta-catenin. Expression of vimentin was strongly correlated with that of K19.CONCLU展开更多
Sirtuins(SIRTs) are NAD+-dependent histone deacetylases and play a role in virtually all cell biological processes. As SIRTs functions vary according to their subtypes, they can either activate or inhibit signaling pa...Sirtuins(SIRTs) are NAD+-dependent histone deacetylases and play a role in virtually all cell biological processes. As SIRTs functions vary according to their subtypes, they can either activate or inhibit signaling pathways upon different conditions or tissues. Recent studies have focused on metabolic effects performed by SIRTs in several cell types since specific metabolic pathways(e.g., aerobic glycolysis, oxidative phosphorylation, β-oxidation, glutaminolysis) are used to determine the cell fate. However, few efforts have been made to understand the role of SIRTs on B lymphocytes metabolism and function. These cells are associated with humoral immune responses by secreting larger amounts of antibodies after differentiating into antibody-secreting cells. Besides, both the SIRTs and B lymphocytes are potential targets to treat several immune-mediated disorders, including cancer. Here, we provide an outlook of recent studies regarding the role of SIRTs in general cellular metabolism and B lymphocytes functions, pointing out the future perspectives of this field.展开更多
A new method was denonstrated to determine stress in a single crystal for multicrystal material and this new method could be specially applied for any symmetric crystalline systems. The strain tensor e was determined ...A new method was denonstrated to determine stress in a single crystal for multicrystal material and this new method could be specially applied for any symmetric crystalline systems. The strain tensor e was determined by the change of the metric tensor G before the initial state and after the deformed state in the crystal reference system. Then stress tensor at grain scale was calculated by the HOOK's law. The stress evaluations were carried out in coarse grains of a thin galvanized coating on a steel substrate during tensile loading. This makes it possible to link the microstructure evolution to the elastic heterogeneity at grain scale or between the grains.展开更多
AIM To evaluate intra- and interobserver agreement in imaging features in inflammatory bowel disease and comparison with fecal calprotectin(FC) levels.METHODS Our institutional computed tomography enterography(CTE) da...AIM To evaluate intra- and interobserver agreement in imaging features in inflammatory bowel disease and comparison with fecal calprotectin(FC) levels.METHODS Our institutional computed tomography enterography(CTE) database was retrospectively queried to identify patients who underwent CTE from January 2014 to June 2015. Patient inclusion criteria were confirmed inflammatory bowel disease(IBD) and FC collected < 4 mo after CTE without any change in clinical treatment or surgical treatment during this interval. The exclusion criterion was poor image quality. Two blinded abdominal radiologists, with 12 and 3 years of experience analyzed the CTE regarding localization(small bowel, colonic, both, or no disease detected);type of IBD(inflammatory, stenosing, fistulizing, > 1 pattern, or normal); and signs of active disease(present or absent). In 42 of 44 patients evaluated, routine CTE reports were made by one of the readers who reevaluated the CTEs ≥ 6 mo later, to determine the intraobserver agreement. FC was considered a sign of disease activity when it was higher than 250 μg/g.RESULTS Forty-four patients with IBD(38 with Crohn's disease and 6 with ulcerative colitis) were included. There was a moderate interobserver agreement regarding localization of IBD(k = 0.540), type of disease(k = 0.410) and the presence of active signs in CTE(k = 0.419). There was almost perfect intraobserver agreement regarding localization, type and signs of active disease in IBD. The k values were 0.902, 0.937 and 0.830, respectively. After a consensus between both radiologists regarding inflammatory activity in CTE, we found that 24(85.7%) of 28 patients who were classified with active disease had elevated FC, and six(37.5%) of 16 patients without inflammatory activity in CTE had elevated FC(P = 0.003). The correlation between elevated FC and the presence of active disease in CTE was significant(k = 0.495, P = 0.001).CONCLUSION We found almost perfect intraobserver and moderate interobserver agreement in the signs of active disease in展开更多
Routing in wireless sensor networks plays a crucial role in deploying and managing an efficient and adaptive network.Ensuring efficient routing entails an ever-increasing necessity for optimized energy consumption and...Routing in wireless sensor networks plays a crucial role in deploying and managing an efficient and adaptive network.Ensuring efficient routing entails an ever-increasing necessity for optimized energy consumption and reliable resource management of both the sensor nodes and the overall sensor network.An efficient routing solution is characterized by its ability to increase network lifetime,enhance efficiency,and ensure the appropriate quality of service.Therefore,the routing protocols need to be designed with an ultimate objective by considering and efficiently managing many characteristics and requirements,such as fault tolerance,scalability,production costs,and others.Unfortunately,many of the existing solutions lead to higher power consumption and communication control overheads,which not only increase network congestion but also decrease network lifetime.In addition,most of these protocols consider a limited number of criteria,in contrast to the complexity and the evolution of WSNs.This paper presents a new adaptive and dynamic multi-criteria routing protocol.Our protocol operates in multi-constraint environments,where most of the current solutions fail to monitor successive and continuous changes in network state and user preferences.This approach provides a routing mechanism,which creates a routing tree based on the evaluation of many criteria.These criteria can cover the topological metrics of neighboring nodes(the role of the nodes in intracommunications,connections between different parts of the network,etc.),the estimated power consumption to reach each direct neighbor,the path length(number of hops to the sink),the remaining energy of individual sensor nodes,and others.These criteria are controlled and supervised dynamically through a detection scheme.In addition,a dynamic selection mechanism,based on multi-attribute decision-making methods,is implemented to build and update the routing tree.In response to changes in the network state,user preferences,and application-defined goals,the election mechani展开更多
Celiac disease is an autoimmune disorder that affects the small intestine of genetically predisposed individuals.Ophthalmic manifestations are within the extra-intestinal manifestations,and can be divided into those o...Celiac disease is an autoimmune disorder that affects the small intestine of genetically predisposed individuals.Ophthalmic manifestations are within the extra-intestinal manifestations,and can be divided into those of autoimmune disorders or those due to absorptive disabilities.This article reviewed the ophthalmologic manifestation of celiac disease.Ophthalmic symptoms are rare,but should be investigated in patients with celiac disease and taken into consideration as the first systemic manifestation.展开更多
Cervical cancer is the second most common cancer in women living in developing countries that account high HPV incidence and mortality rates. Vaccinating girls between 9 and 14 years old is supposed to be the most cos...Cervical cancer is the second most common cancer in women living in developing countries that account high HPV incidence and mortality rates. Vaccinating girls between 9 and 14 years old is supposed to be the most cost-effective public health approach against cervical cancer. This systematic review aims to assess the application and coverage of the HPV vaccine in developing countries and identify the main challenges for the introduction of the vaccine in these settings. Eligible studies were selected according to the defined inclusion and exclusion criteria. To determine the quality of the studies was employed the STROBE checklist. This review included seven studies, encompassing the analysis of 19 countries and 112,116 girls aged from 9 to 18 years old. The coverage of HPV vaccination ranged from 13.8% to 107.4%, with most of the programs having more than 60% of coverage, which reflects a high percentage of vaccinated girls. The main challenges were lack of knowledge and worries about the vaccine, insufficient financial resources and staff workers, lack of community involvement and dissemination of important information about HPV. In developing countries that implemented the HPV vaccine, high coverage rates were achieved, despite sociocultural, economic and political challenges. In the future, studies that analyze the coverage rates after the elimination of the barriers and the repercussions on the mortality rates should be conducted, so that more developing countries have the opportunity to efficiently implement the vaccine.展开更多
Ⅰ The following two theorems on monotone functions have been proved recently by Prof. Chuang. Theorem A. Suppose that a positive function f（x） is monotone non-decreasing in an interval x ≥ x0 with the property li...Ⅰ The following two theorems on monotone functions have been proved recently by Prof. Chuang. Theorem A. Suppose that a positive function f（x） is monotone non-decreasing in an interval x ≥ x0 with the property lim f（x） = ∞. Let α, β be two numbers satis-展开更多
This paper reports that an atomic scale study of [^-110] symmetrical tilt grain boundary （STGB） has been made with modified analytical embedded atom method （MAEAM） for 44 planes in three noble metals Au, Ag and Cu...This paper reports that an atomic scale study of [^-110] symmetrical tilt grain boundary （STGB） has been made with modified analytical embedded atom method （MAEAM） for 44 planes in three noble metals Au, Ag and Cu. For each metal, the energies of two crystals ideally joined together are unrealistically hlgh due to very short distance between atoms near the grain boundary （GB） plane. A relative slide between grains in the GB plane results in a significaut decrease in GB energy and a minimum value is obtained at specific translation distance. The minimum energy of Cu is much higher than that of Ag and Au, while the minimum energy of Ag is slightly higher than that of Au. For all the three metals, the three lowest energies correspond to identical （111）, （113） and （331） boundary successively for two translations considered; from minimization of GB energy, these boundaries should be preferable in [^-110] STGB for noble metals. This is consistent with the experimental results. In addition, the minimum energy increases with increasing reciprocal planar coincidence density ∑, but decreases with increasing relative interplanar distance d/a.展开更多
Animal models and clinical studies have shown that helminth infections exert immunomodulatory activity,altering intestinal permeability and providing a potential beneficial action on autoimmune and inflammatory disord...Animal models and clinical studies have shown that helminth infections exert immunomodulatory activity,altering intestinal permeability and providing a potential beneficial action on autoimmune and inflammatory disorders in human beings,such as inflammatory bowel disease(IBD) and celiac disease. This is consistent with the theory that intestinal microbiota is responsible for shaping human immunological responses. With the arrival of the immunobiologic era and the use of antibodies,we propose a distinctive pathway for treating patients with IBD and celiac disease. We have some evidence about the safety and tolerability of helminth use,but evidence about their impact on disease activity is lacking. Using worms to treat diseases could be a possible way to lower treatment costs,since the era of immunobiologic agents is responsible for a significant rise in expenses. Some questions remain to be investigated regarding the use of helminths in intestinal disease,such as the importance of the specific species of helminths used,appropriate dosing regimens,optimal timing of treatment,the role of host genetics,diet,environment,and the elucidation of the exact mechanisms of action. One promising approach is the use of helminth-derived anti-inflammatory molecules as drugs. Yet there are still many challenges with this method,especially with regard to safety. Studies on intestinal permeability point to Strongyloides stercoralis as a useful nematode for these purposes.展开更多
Aim: Shigella flexneri (S. flexneri) is a gram-negative enterobacterium responsible for severe intestinal end systemic infection in humans. The bacteria can reach the liver due to degeneration of the colonic epitheliu...Aim: Shigella flexneri (S. flexneri) is a gram-negative enterobacterium responsible for severe intestinal end systemic infection in humans. The bacteria can reach the liver due to degeneration of the colonic epithelium. Hypoxia is present in many human diseases and can induce the expression of the transcription factor HIF-1alpha that may have a cell protective role. The influence of hypoxia and HIF-1alpha on bacterial infection, studied in this work, is unclear. Hypoxia inducible factor-1alpha (HIF-1alpha) is a transcription factor that acts as a master regulator of gene expression induced by hypoxia. Methods: We compared the ability of S. flexneri to invade rat hepatocytes in primary culture both in normoxic and hypoxic conditions. We evaluated TNF-alpha released by hepatocytes, apoptosis rate and HIF-1alpha expression by confocal microscopy as well as real time PCR technique. Results: We showed that S. flexneri invaded less hepatocytes previously submitted to 24 h hypoxia (6.5% O2) than those cultivated in normoxia (21% O2). S. flexneri also induced HIF-1α expression in hepatocytes, TNF-α secretion and apoptosis. Conclusion: a) Hypoxia alone was not a stimulus to TNF-α secretion, but induced cell apoptosis and HIF-1α expression;b) S. flexneri was able to invade rat hepatocytes and hypoxia apparently influenced significantly bacterial cell invasiveness;c) HIF-1α was expressed in hypoxic conditions, and it was also stimulated by S. flexneri.展开更多
This paper is a continuation of the research carried out in [1]-[2], where the robustnessanalysis for stochastic approximation algorithms is given for two cases: 1. The regression functionand the Liapunov function are...This paper is a continuation of the research carried out in [1]-[2], where the robustnessanalysis for stochastic approximation algorithms is given for two cases: 1. The regression functionand the Liapunov function are not zero at the sought-for x^0, 2. lim supnot zero, here {ξ_i} are the measurement errors and {a_n} are the weighting coefficients in thealgorithm. Allowing these deviations from zero to occur simultaneously but to remain small, thispaper shows that the estimation error is still small even for a class fo measurement errors moregeneral than that considered in [2].展开更多
Studies were carried out on several aspects of rare earth elements （REEs）, such as the theory and practice of their applications in agriculture, their geochemical behaviors in natural and agricultural ecosystems, th...Studies were carried out on several aspects of rare earth elements （REEs）, such as the theory and practice of their applications in agriculture, their geochemical behaviors in natural and agricultural ecosystems, the mechanisms for the increase of crop yield using REE fertilizer, and their toxicology. However, limited knowledge was available for the transfer processes and the features and mechanisms of distribution and fractionations of REEs inside plants. The characteristics of REE fractionations in plants can be used to ＂trace＂ the pathway of REE transportation from soils （solution） to plants. A better understanding of the mechanisms of REE fractionations was helpful to investigate the controlling factors, including both the internal and the external ones. The characteristics and mechanisms of REE fractionations in plants and their significance were reviewed. Furthermore, the prospect for these fields was discussed, in hope of providing a new way in studying the bioavailability of REEs and heavy metals.展开更多
文摘AIM： To determine the prevalence of celiac disease in a group of volunteer blood donors at a blood bank in the city of Curitiba, Brazil through detection of the serum marker immunoglobulin A （IgA） antitransglutaminase antibody. METHODS： Blood samples collected from 2086 healthy subjects at the Paraná State Center for Hematology and Hemotherapy in Curitiba were submitted to ELISA testing for the IgA antitransglutaminase antibody. Positive samples received IgA antiendomysium antibody test through indirect immunofluorescence using human umbilical cord as substrate. Subsequently, patients who were positive on both tests underwent small bowel （distal duodenum） biopsy. RESULTS： Six subjects, four males and two females, tested positive for the two serum markers. Five of the six were submitted to intestinal biopsy （one declined the procedure）. Biopsy results revealed changes in the distal duodenum mucosa （three classified as Marsh mb lesions and two as Marsh Ⅱ lesions）. Most donors diagnosed having celiac disease presented multiple symptoms （gastrointestinal tract complaints）. One donor reported having a family history of celiac disease （in a niece）. CONCLUSION： Among apparently healthy blood donors,the prevalence of biopsy-confirmed celiac disease was approximately 1：417, similar to that seen in European countries.
文摘Regulatory T cells （Tregs） are a specialized subpopulation of T cells that control the immune response and thereby maintain immune system homeostasis and tolerance to self-antigens. Many subsets of CD4＋ Tregs have been identified, including Foxp3~, Trl, Th3, and Foxp3neg iT（R）35 cells. In this study, we identified a new subset of CD4＋VEGFR1high Tregs that have immunosuppressive capacity. CD4＋VEGFRlhigh T cells, which constitute approximately 1.0% of CD4＋ T cells, are hyporesponsive to T-cell antigen receptor stimulation. Surface marker and FoxP3 expression analysis revealed that CD4＋VEGFR1high T cells are distinct from known Tregs. CD4＋VEGFR1high T cells suppressed the proliferation of CD4＋CD25- T cell as efficiently as CD4＋CD25high natural Tregs in a contact-independent manner. Furthermore, adoptive transfer of CD4＋VEGFR1＋ T cells from wild type to RAG-2-deficient C57BL/6 mice inhibited effector T-cell-mediated inflammatory bowel disease. Thus, we report CD4＋ VEGFR1high T cells as a novel subset of Tregs that regulate the inflammatory response in the intestinal tract.
基金Sao Paulo Research Foundation-FAPESP(grant 2011/02633-5 and 2013/13347-9)Mathematics of Information Technology and Complex Systems-Mitacs for partial financial support.
文摘Brazil is one of the highest endemic countries for Zoonotic Visceral Leishmaniasis:according to the Brazilian Ministry of Health,the annual number of new human cases and deaths due to this disease has been increasing for the last 20 years.In addition,regarding the Americas,the specific relationship between canine and human for Visceral Leishmaniasis dynamics is still not well understood.In this work we propose a new model for Zoonotic Visceral Leishmaniasis,based on the models previously published by Burattini et al.(1998)and Ribas et al.(2013).Herein,we modeled the disease dynamics using a modified set of differential equations from those two authors,considering the same assumptions(inclusion of human,dog and sandfly populations,all constants over time).From this set of equations we were able to calculate the basic reproduction number R 0 and to analyze the stability and sensitivity of the system to the parameters variability.As main result,when the stability of the system is reached,the normalized reporting human cases rate is estimated in 9.12E-08/day.This estimation is very close to the 2015 report from Araçatuba city,5.69E-08/day.We also observed from stability and sensitivity analysis that the activity of sandfly population is critical to introduction and maintenance of Zoonotic Visceral Leishmaniasis in the population.In addition,the importance of dog as source of infection concentrates on latent dog,since it does not show clinical symptoms and signs and,therefore,has a great contribution to disease dissemination.As conclusion,considering the presently ethical issues regarding to elimination of positive dog in Brazil and the highly sensitivity of disease dynamics on sandfly population,we recommend that the sandfly population control should be prioritized.
基金Supported by LIMs 01 and 37-HCFMUSP, CNPq and FAPESP
文摘AIM: To simulate a hypothetical increase of 50% in the number of pancreas-kidney (PK) transplantations using less-than-ideal donors by a mathematical model. METHODS: We projected the size of the waiting list by taking into account the incidence of new patients per year, the number of PK transplantations carried out in the year and the number of patients who died on the waiting list or were removed from the list for other reasons. These variables were treated using a model developed elsewhere. RESULTS: We found that the waiting list demand will meet the number of PK transplantation by the year 2022. CONCLUSION: In future years, it is perfectly possible to minimize the waiting list time for pancreas transplantation through expansion of the donor pool using less-than-ideal donors.
基金Supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo,No.08/58855-3 to Alves VAF
文摘AIM: To assess the distribution of proteins coded by genes reported as relevant for the molecular classification of hepatocellular carcinoma (HCC).METHODS: In this retrospective cross-sectional study, the following clinicopathological data were analyzed in 80 autopsied HCC patients: sex, age, ethnicity, alcohol intake, infection with hepatitis B and/or C virus, infection with human immunodeficiency virus, prior treatment, basic and immediate causes of death, liver weight, presence of cirrhosis, number and size of nodules, gross pattern, histological grade and variants, architectural pattern, invasion of large veins, and presence and location of extrahepatic metastases. The protein products of genes known to be involved in molecular pathogenesis of HCC, including epidermal growth factor receptor (EGFR), MET, keratin 19 (K19), vimentin, beta-catenin, mechanistic target of rapamycin (mTOR), extracellular signaling-related kinase (ERK)1, ERK2, Ki67, cyclin D1, caspase 3 and p53, were detected by immunohistochemistry on tissue microarrays. The expression levels were scored and statistically assessed for correlation with HCC parameters.RESULTS: Infection with hepatitis C virus was identified in 49% of the 80 autopsy patients, cirrhosis in 90%, advanced tumors in 95%, and extrahepatic metastases in 38%. Expression of K19, p53 and ERK1 correlated to high-grade lesions. Expression of ERK1, nuclear beta-catenin, cyclin D1 and ERK2 correlated to higher rates of cell proliferation as determined by Ki67. Expression of MET, EGFR (> 0) and caspase 3 correlated with lower histological grades. Expression of EGFR correlated to that of caspase 3, and overexpression of EGFR (≥ 200/300) was observed in low-grade tumors more frequently (grades 1 and 2: 67% vs grade 3: 27% and grade 4: 30%). Expression of ERK1 was associated with that of K19 and vimentin, whereas expression of ERK2 was associated with that of cyclin D1, MET and membrane beta-catenin. Expression of vimentin was strongly correlated with that of K19.CONCLU
基金Supported by Fundacao de AmparoàPesquisa de Sao Paulo(FAPESP)under Agreements,No.2015/26682-6,No.2017/03248-4and No.2017/05264-7financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nível Superior–Brasil(CAPES)–Finance Code 001
文摘Sirtuins(SIRTs) are NAD+-dependent histone deacetylases and play a role in virtually all cell biological processes. As SIRTs functions vary according to their subtypes, they can either activate or inhibit signaling pathways upon different conditions or tissues. Recent studies have focused on metabolic effects performed by SIRTs in several cell types since specific metabolic pathways(e.g., aerobic glycolysis, oxidative phosphorylation, β-oxidation, glutaminolysis) are used to determine the cell fate. However, few efforts have been made to understand the role of SIRTs on B lymphocytes metabolism and function. These cells are associated with humoral immune responses by secreting larger amounts of antibodies after differentiating into antibody-secreting cells. Besides, both the SIRTs and B lymphocytes are potential targets to treat several immune-mediated disorders, including cancer. Here, we provide an outlook of recent studies regarding the role of SIRTs in general cellular metabolism and B lymphocytes functions, pointing out the future perspectives of this field.
文摘A new method was denonstrated to determine stress in a single crystal for multicrystal material and this new method could be specially applied for any symmetric crystalline systems. The strain tensor e was determined by the change of the metric tensor G before the initial state and after the deformed state in the crystal reference system. Then stress tensor at grain scale was calculated by the HOOK's law. The stress evaluations were carried out in coarse grains of a thin galvanized coating on a steel substrate during tensile loading. This makes it possible to link the microstructure evolution to the elastic heterogeneity at grain scale or between the grains.
文摘AIM To evaluate intra- and interobserver agreement in imaging features in inflammatory bowel disease and comparison with fecal calprotectin(FC) levels.METHODS Our institutional computed tomography enterography(CTE) database was retrospectively queried to identify patients who underwent CTE from January 2014 to June 2015. Patient inclusion criteria were confirmed inflammatory bowel disease(IBD) and FC collected < 4 mo after CTE without any change in clinical treatment or surgical treatment during this interval. The exclusion criterion was poor image quality. Two blinded abdominal radiologists, with 12 and 3 years of experience analyzed the CTE regarding localization(small bowel, colonic, both, or no disease detected);type of IBD(inflammatory, stenosing, fistulizing, > 1 pattern, or normal); and signs of active disease(present or absent). In 42 of 44 patients evaluated, routine CTE reports were made by one of the readers who reevaluated the CTEs ≥ 6 mo later, to determine the intraobserver agreement. FC was considered a sign of disease activity when it was higher than 250 μg/g.RESULTS Forty-four patients with IBD(38 with Crohn's disease and 6 with ulcerative colitis) were included. There was a moderate interobserver agreement regarding localization of IBD(k = 0.540), type of disease(k = 0.410) and the presence of active signs in CTE(k = 0.419). There was almost perfect intraobserver agreement regarding localization, type and signs of active disease in IBD. The k values were 0.902, 0.937 and 0.830, respectively. After a consensus between both radiologists regarding inflammatory activity in CTE, we found that 24(85.7%) of 28 patients who were classified with active disease had elevated FC, and six(37.5%) of 16 patients without inflammatory activity in CTE had elevated FC(P = 0.003). The correlation between elevated FC and the presence of active disease in CTE was significant(k = 0.495, P = 0.001).CONCLUSION We found almost perfect intraobserver and moderate interobserver agreement in the signs of active disease in
文摘Routing in wireless sensor networks plays a crucial role in deploying and managing an efficient and adaptive network.Ensuring efficient routing entails an ever-increasing necessity for optimized energy consumption and reliable resource management of both the sensor nodes and the overall sensor network.An efficient routing solution is characterized by its ability to increase network lifetime,enhance efficiency,and ensure the appropriate quality of service.Therefore,the routing protocols need to be designed with an ultimate objective by considering and efficiently managing many characteristics and requirements,such as fault tolerance,scalability,production costs,and others.Unfortunately,many of the existing solutions lead to higher power consumption and communication control overheads,which not only increase network congestion but also decrease network lifetime.In addition,most of these protocols consider a limited number of criteria,in contrast to the complexity and the evolution of WSNs.This paper presents a new adaptive and dynamic multi-criteria routing protocol.Our protocol operates in multi-constraint environments,where most of the current solutions fail to monitor successive and continuous changes in network state and user preferences.This approach provides a routing mechanism,which creates a routing tree based on the evaluation of many criteria.These criteria can cover the topological metrics of neighboring nodes(the role of the nodes in intracommunications,connections between different parts of the network,etc.),the estimated power consumption to reach each direct neighbor,the path length(number of hops to the sink),the remaining energy of individual sensor nodes,and others.These criteria are controlled and supervised dynamically through a detection scheme.In addition,a dynamic selection mechanism,based on multi-attribute decision-making methods,is implemented to build and update the routing tree.In response to changes in the network state,user preferences,and application-defined goals,the election mechani
文摘Celiac disease is an autoimmune disorder that affects the small intestine of genetically predisposed individuals.Ophthalmic manifestations are within the extra-intestinal manifestations,and can be divided into those of autoimmune disorders or those due to absorptive disabilities.This article reviewed the ophthalmologic manifestation of celiac disease.Ophthalmic symptoms are rare,but should be investigated in patients with celiac disease and taken into consideration as the first systemic manifestation.
文摘Cervical cancer is the second most common cancer in women living in developing countries that account high HPV incidence and mortality rates. Vaccinating girls between 9 and 14 years old is supposed to be the most cost-effective public health approach against cervical cancer. This systematic review aims to assess the application and coverage of the HPV vaccine in developing countries and identify the main challenges for the introduction of the vaccine in these settings. Eligible studies were selected according to the defined inclusion and exclusion criteria. To determine the quality of the studies was employed the STROBE checklist. This review included seven studies, encompassing the analysis of 19 countries and 112,116 girls aged from 9 to 18 years old. The coverage of HPV vaccination ranged from 13.8% to 107.4%, with most of the programs having more than 60% of coverage, which reflects a high percentage of vaccinated girls. The main challenges were lack of knowledge and worries about the vaccine, insufficient financial resources and staff workers, lack of community involvement and dissemination of important information about HPV. In developing countries that implemented the HPV vaccine, high coverage rates were achieved, despite sociocultural, economic and political challenges. In the future, studies that analyze the coverage rates after the elimination of the barriers and the repercussions on the mortality rates should be conducted, so that more developing countries have the opportunity to efficiently implement the vaccine.
文摘Ⅰ The following two theorems on monotone functions have been proved recently by Prof. Chuang. Theorem A. Suppose that a positive function f（x） is monotone non-decreasing in an interval x ≥ x0 with the property lim f（x） = ∞. Let α, β be two numbers satis-
基金Project supported by the State Key Development for Basic Research of China （Grant No 2004CB619302） and the National Natural Science Foundation of China （Grant No 50271038）.
文摘This paper reports that an atomic scale study of [^-110] symmetrical tilt grain boundary （STGB） has been made with modified analytical embedded atom method （MAEAM） for 44 planes in three noble metals Au, Ag and Cu. For each metal, the energies of two crystals ideally joined together are unrealistically hlgh due to very short distance between atoms near the grain boundary （GB） plane. A relative slide between grains in the GB plane results in a significaut decrease in GB energy and a minimum value is obtained at specific translation distance. The minimum energy of Cu is much higher than that of Ag and Au, while the minimum energy of Ag is slightly higher than that of Au. For all the three metals, the three lowest energies correspond to identical （111）, （113） and （331） boundary successively for two translations considered; from minimization of GB energy, these boundaries should be preferable in [^-110] STGB for noble metals. This is consistent with the experimental results. In addition, the minimum energy increases with increasing reciprocal planar coincidence density ∑, but decreases with increasing relative interplanar distance d/a.
文摘Animal models and clinical studies have shown that helminth infections exert immunomodulatory activity,altering intestinal permeability and providing a potential beneficial action on autoimmune and inflammatory disorders in human beings,such as inflammatory bowel disease(IBD) and celiac disease. This is consistent with the theory that intestinal microbiota is responsible for shaping human immunological responses. With the arrival of the immunobiologic era and the use of antibodies,we propose a distinctive pathway for treating patients with IBD and celiac disease. We have some evidence about the safety and tolerability of helminth use,but evidence about their impact on disease activity is lacking. Using worms to treat diseases could be a possible way to lower treatment costs,since the era of immunobiologic agents is responsible for a significant rise in expenses. Some questions remain to be investigated regarding the use of helminths in intestinal disease,such as the importance of the specific species of helminths used,appropriate dosing regimens,optimal timing of treatment,the role of host genetics,diet,environment,and the elucidation of the exact mechanisms of action. One promising approach is the use of helminth-derived anti-inflammatory molecules as drugs. Yet there are still many challenges with this method,especially with regard to safety. Studies on intestinal permeability point to Strongyloides stercoralis as a useful nematode for these purposes.
文摘Aim: Shigella flexneri (S. flexneri) is a gram-negative enterobacterium responsible for severe intestinal end systemic infection in humans. The bacteria can reach the liver due to degeneration of the colonic epithelium. Hypoxia is present in many human diseases and can induce the expression of the transcription factor HIF-1alpha that may have a cell protective role. The influence of hypoxia and HIF-1alpha on bacterial infection, studied in this work, is unclear. Hypoxia inducible factor-1alpha (HIF-1alpha) is a transcription factor that acts as a master regulator of gene expression induced by hypoxia. Methods: We compared the ability of S. flexneri to invade rat hepatocytes in primary culture both in normoxic and hypoxic conditions. We evaluated TNF-alpha released by hepatocytes, apoptosis rate and HIF-1alpha expression by confocal microscopy as well as real time PCR technique. Results: We showed that S. flexneri invaded less hepatocytes previously submitted to 24 h hypoxia (6.5% O2) than those cultivated in normoxia (21% O2). S. flexneri also induced HIF-1α expression in hepatocytes, TNF-α secretion and apoptosis. Conclusion: a) Hypoxia alone was not a stimulus to TNF-α secretion, but induced cell apoptosis and HIF-1α expression;b) S. flexneri was able to invade rat hepatocytes and hypoxia apparently influenced significantly bacterial cell invasiveness;c) HIF-1α was expressed in hypoxic conditions, and it was also stimulated by S. flexneri.
基金This project is supported by the National Natural Science Foundation of China
文摘This paper is a continuation of the research carried out in [1]-[2], where the robustnessanalysis for stochastic approximation algorithms is given for two cases: 1. The regression functionand the Liapunov function are not zero at the sought-for x^0, 2. lim supnot zero, here {ξ_i} are the measurement errors and {a_n} are the weighting coefficients in thealgorithm. Allowing these deviations from zero to occur simultaneously but to remain small, thispaper shows that the estimation error is still small even for a class fo measurement errors moregeneral than that considered in [2].
基金Project supported by the National Natural Science Foundation of China (40571146)
文摘Studies were carried out on several aspects of rare earth elements （REEs）, such as the theory and practice of their applications in agriculture, their geochemical behaviors in natural and agricultural ecosystems, the mechanisms for the increase of crop yield using REE fertilizer, and their toxicology. However, limited knowledge was available for the transfer processes and the features and mechanisms of distribution and fractionations of REEs inside plants. The characteristics of REE fractionations in plants can be used to ＂trace＂ the pathway of REE transportation from soils （solution） to plants. A better understanding of the mechanisms of REE fractionations was helpful to investigate the controlling factors, including both the internal and the external ones. The characteristics and mechanisms of REE fractionations in plants and their significance were reviewed. Furthermore, the prospect for these fields was discussed, in hope of providing a new way in studying the bioavailability of REEs and heavy metals.
