Search

Detrusor pressure-volume relationship evaluation by urodynamics provides useful clinical information; however, it is invasive, and requires specific installations. An alternative technique proposed by our research group is the electrical bioimpedance (BI) which is an easily performed and non-invasive method. In this work, we assess the relationship between BI and detrusor bladder pressure in adults with neurogenic lower urinary tract dysfunction.A prospective observational study was conducted. 20 patients (11 females and 9 male) previously diagnosed with neurogenic bladder were included. All participants underwent simultaneously a urodynamic evaluation (UDS) and BI determination, and both examination signals were recorded and subjected to Shapiro-Wilks statistical test. A correlational statistical test was used to compare the pressure parameters (detrusor, vesical and abdominal) with their respective BI determinations. Subsequently, a linear regression test was performed to evaluate the concordance between BI and their respective pressure values.From the 20 correlations, between detrusor bladder pressure (PDET) and abdominal bioimpedance determinations (ZABD), obtained for all participants, 16 evidenced significant results over 90% (p 0.05).A significantly high correlation between abdominal bioimpedance determinations and the detrusor bladder pressures was evidenced. These results should be confirmed in a larger group of participants.

Epigenetic mechanisms such as histone acetylation and deacetylation participate in regulation of the genes involved in encystation of Entamoeba invadens. However, the histones and target residues involved, and whether the acetylation and deacetylation of the histones leads to the regulation of gene expression associated with the encystation of this parasite, remain unknown. In this study, we found that E. invadens histone H4 is acetylated in both stages of the parasite and is more highly acetylated during the trophozoite stage than in the cyst. Histone hyperacetylation induced by Trichostatin A negatively affects the encystation of E. invadens, and this inhibition is associated with the downregulation of the expression of genes implicated in the synthesis of chitin, polyamines, gamma-aminobutyric acid pathways and cyst wall proteins, all of which are important in the formation of cysts. Finally, in silico analysis and activity assays suggest that a class I histone deacetylase (EiHDAC3) could be involved in control of the expression of a subset of genes that are important in several pathways during encystation. Therefore, the identification of enzymes that acetylate and/or deacetylate histones that control encystation in E. invadens could be a promising therapeutic target for preventing transmission of other amoebic parasites such as E. histolytica, the causative agent of amoebiasis in humans.

JCR Web of Science; Year: 2020 in Categories: Public, Environmental & Occupational Health: Q1, Current Impact Factor: 3.390, 5-year Impact Factor: 3.789., Background: treating infectious diseases in elderly individuals is difficult; patient referral to emergency services often occurs, since the elderly tend to arrive at consultations with advanced, serious symptoms. Aim: it was hypothesized that anticipating an infectious disease diagnosis by a few days could significantly improve a patient?s well-being and reduce the burden on emergency health system services. Methods: vital signs from residents were taken daily and transferred to a database in the cloud. Classifiers were used to recognize patterns in the spatial domain process of the collected data. Doctors reported their diagnoses when any disease presented. A flexible microservice architecture provided access and functionality to the system. Results: combining two different domains, health and technology, is not easy, but the results are encouraging. The classifiers reported good results; the system has been well accepted by medical personnel and is proving to be cost-effective and a good solution to service disadvantaged areas. In this context, this research found the importance of certain clinical variables in the identification of infectious diseases. Conclusions: this work explores how to apply mobile communications, cloud services, and machine learning technology, in order to provide efficient tools for medical staff in nursing homes. The scalable architecture can be extended to big data applications that may extract valuable knowledge patterns for medical research., European Commission

The derelict Remance gold mine is a possible source of pollution with potentially toxic elements (PTEs). In the study area, diverse mine waste has been left behind and exposed to weather conditions, and poses risks for soil, plants and water bodies, and also for the health of local inhabitants. This study sought to perform an ecological and health risk assessment of derelict gold mining areas with incomplete remediation, including: (i) characterizing the geochemical distribution of PTEs, (ii) assessing ecological risk by estimating the pollution load index (PLI) and potential ecological risk index (RI), (iii) assessing soil health by dehydrogenase activity, and iv) establishing non-carcinogenic (HI) and carcinogenic risks (CR) for local inhabitants. Soil health seems to depend on not only PTE concentrations, but also on organic matter (OM). Both indexes (PLI and RI) ranged from high to extreme near mining and waste accumulation sites. As indicated by both the HI and CR results, the mining area poses a health risk for local inhabitants and particularly for children. For this reason, it will be necessary to set up environmental management programs in the areas that are most affected (tailings and surrounding areas) and accordingly establish the best remediation strategies to minimize risks for the local population.

While stress has been implicated in functional dyspepsia (FD), the mechanisms by which stress results in symptoms are not well defined. The aim of the current study was to assess gastric myoelectric and autonomic changes in response to a physical stressor in youth with FD. In a group of healthy controls and pediatric FD subjects, we recorded ECG and EGG signals 30 min before and 60 min after, a cold pressor task (CPT). Gastric EGG and heart rate variability (HRV) parameters were calculated in pre- and post-CPT stages and in short intervals. The pre-CPT percent tachygastria was higher in FD subjects as compared to controls. However, CPT did not induce any EGG changes in either controls or FD subjects and the two groups did not differ from each other post-CPT. The CPT resulted in an increase in HRV and standard deviation of NN intervals in controls; there was no change in any HRV parameter in FD subjects. Acute physical stress does not appear to induce gastric electrical abnormalities in youth with FD. Youth with FD appear to lack the normal flexible autonomic response to a physical stressor.

Obesity and periodontitis are among the most common non-communicable diseases, and epidemiological studies report the influence of obesity in the onset and progression of periodontitis. Data indicate that increased body mass index, waist circumference, percentage of subcutaneous body fat, and serum lipid levels are associated with increased risk to develop periodontitis. The underlying biological mechanisms of this association involve adipose tissue-derived cytokines, such as tumour necrosis factor-α and interleukin-6, which affect whole-body metabolism and contribute to the development of a low-grade systemic inflammation. Multiple studies report a positive association between these two diseases across diverse populations. Obesity does not appear to impair the success of periodontal therapy. However, currently available evidence is variable and therefore inconclusive. Despite the limited evidence about recommendations on treatment planning, oral healthcare professionals need to be aware of the complexity of obesity to counsel their patients about the importance of maintaining healthy body weight and performing good oral hygiene procedures.

Pancreatic cancer is highly lethal and has a poor prognosis. The most common alteration during the formation of pancreatic tumors is the activation of KRAS (Kirsten rat sarcoma 2 viral oncogene homolog) oncogene. As a new therapeutic strategy, the C19 molecule ((2S)

A patient suffering from advanced chronic renal disease undergoes several dialysis sessions on different dates. Several clinical parameters are monitored during the different hours of any of these sessions. These parameters, together with the information provided by other parameters of analytical nature, can be very useful to determine the probability that a patient may suffer from hypotension during the session, which should be specially watched since it represents a proven factor of possible mortality. However, the analytical information is not always available to the healthcare personnel, or it is far in time, so the clinical parameters monitored during the session become key to the prevention of hypotension. This article presents an investigation to predict the appearance of hypotension during a dialysis session, using predictive models trained from a large dialysis database, which contains the clinical information of 98,015 sessions corresponding to 758 patients. The prediction model takes into account up to 22 clinical parameters measured five times during the session, as well as the gender and age of the patient. This model was trained by means of machine learning classifiers, providing a success in the prediction higher than 80%.

PurposeCOVID-19 pandemic has multifaceted presentations with rising evidence of immune-mediated mechanisms underplay. We sought to explore the outcomes of severe COVID-19 patients treated with a multi-mechanism approach (MMA) in addition to standard-of-care (SC) versus patients who only received SC treatment.Materials and methodsData were collected retrospectively for patients admitted to the intensive care unit (ICU). This observational cohort study was performed at five institutions, 3 in the United States and 2 in Honduras. Patients were stratified for MMA vs. SC treatment during ICU stay. MMA treatment consists of widely available medications started immediately upon hospitalization. These interventions target immunomodulation, anticoagulation, viral suppression, and oxygenation. Primary outcomes included in-hospital mortality and length of stay (LOS) for the index hospitalization and were measured using logistic regression.ResultsOf 86 patients admitted, 65 (76%) who had severe COVID-19 were included in the study; 30 (46%) patients were in SC group, compared with 35 (54%) patients treated with MMA group. Twelve (40%) patients in the SC group died, compared with 5 (14%) in the MMA group (p-value = 0.01, Chi squared test). After adjustment for gender, age, treatment group, Q-SOFA score, the MMA group had a mean length of stay 8.15 days, when compared with SC group with 13.55 days. ICU length of stay was reduced by a mean of 5.4 days (adjusted for a mean age of 54 years, p-value 0.03) and up to 9 days (unadjusted for mean age), with no significant reduction in overall adjusted mortality rate, where the strongest predictor of mortality was the use of mechanical ventilation.ConclusionThe finding that MMA decreases the average ICU length of stay by 5.4 days and up to 9 days in older patients suggests that implementation of this treatment protocol could allow a healthcare system to manage 60% more COVID-19 patients with the same number of ICU beds.

Background Meal-related symptoms are common in paediatric functional dyspepsia (FD). There are only a small number of paediatric studies assessing mechanisms for meal-related symptoms, and these have not utilized Rome IV criteria. The aim of the current study was to assess gastric myoelectric and autonomic nervous system (ANS) responses to both liquid and solid meals in youth with Rome IV-defined FD. Methods In healthy controls (N = 14) and youth with FD (N = 12), we recorded electrocardiograph (to assess heart rate variability; HRV) and electrogastrograph (EGG) signals before and after two test meals, one liquid and one solid. EGG parameters and HRV were assessed for the entire pre- and postprandial periods and in short time intervals. Additionally, liquid gastric emptying was assessed utilizing a 13 C-acetate breath test. Key results During the EGG, the dominant power increased with both meals in controls but not patients with FD. During HRV assessment, the low frequency to high frequency ratio was higher after the liquid meal in controls, despite being similar preprandial, as compared to patients with FD. In controls, both standard deviation of normal to normal waves (SDNN) and root mean square of successive ECG R peaks (R-R interval) differences (rMSSD) increased after the liquid meal (but not after the solid meal) in controls but not patients with FD. Conclusions and inferences Youth with Rome IV-defined FD lacks the normal postprandial EGG dominant power response or autonomic nervous system response following a liquid meal. The latter appears to indicate a lack of ANS flexibility.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most intractable and devastating malignant tumors. Epigenetic modifications such as DNA methylation and histone modification regulate tumor initiation and progression. However, the contribution of histone variants in PDAC is unknown. Here, we demonstrated that the histone variant H2A.Z is highly expressed in PDAC cell lines and PDAC patients and that its overexpression correlates with poor prognosis. Moreover, all three H2A.Z isoforms (H2A.Z.1, H2A.Z.2.1, and H2A.Z.2.2) are highly expressed in PDAC cell lines and PDAC patients. Knockdown of these H2A.Z isoforms in PDAC cell lines induces a senescent phenotype, cell cycle arrest in phase G2/M, increased expression of cyclin-dependent kinase inhibitor CDKN2A/p16, SA-β-galactosidase activity and interleukin 8 production. Transcriptome analysis of H2A.Z-depleted PDAC cells showed altered gene expression in fatty acid biosynthesis pathways and those that regulate cell cycle and DNA damage repair. Importantly, depletion of H2A.Z isoforms reduces the tumor size in a mouse xenograft model in vivo and sensitizes PDAC cells to gemcitabine. Overexpression of H2A.Z.1 and H2A.Z.2.1 more than H2A.Z.2.2 partially restores the oncogenic phenotype. Therefore, our data suggest that overexpression of H2A.Z isoforms enables cells to overcome the oncoprotective barrier associated with senescence, favoring PDAC tumor grow and chemoresistance. These results make H2A.Z a potential candidate as a diagnostic biomarker and therapeutic target for PDAC.

Actin is one of the most conserved, abundant, and ubiquitous proteins in all eukaryotes characterised to date. Posttranslation modifications of actin modify the organisation of the actin-rich cytoskeleton. In particular, chemical modifications of actin's amino-terminal region determine how filamentous actin is organised into scaffolds. After assuming that protein modifications account for the multiple functional activities exerted by the single actin in Entamoeba histolytica, we profiled posttranslational modifications of this protein. Acetylation (on 21 different amino acids) was the most abundant modification, followed by phosphorylation. Furthermore, the glycine residue at Position 2 in E. histolytica's actin (Gly2, not found in most other eukaryotic actins) was found to be acetylated. The impact of Gly2 on the amoeba's life cycle and pathogenicity was then assessed in mutagenesis experiments. We found that Gly2 was necessary for cell morphology and division, parasite-host cell adhesion, and host invasion in an in vitro model of amoebic human infection.

Background The GTPase KRas4B has been utilized as a principal target in the development of anticancer drugs. PDE6δ transports KRas4B to the plasma membrane, where it is released to activate various signaling pathways required for the initiation and maintenance of cancer. Therefore, identifying new small molecules that prevent activation of this GTPase by stabilizing the KRas4B-PDE6δ molecular complex is a practical strategy to fight against cancer. Methods The crystal structure of the KRas4B-PDE6δ heterodimer was employed to locate possible specific binding sites at the protein-protein interface region. Virtual screening of Enamine-database compounds was performed on the located potential binding sites to identify ligands able to simultaneously bind to the KRas4B-PDE6δ heterodimer. A molecular dynamics approach was used to estimate the binding free-energy of the complex. Cell viability and apoptosis were measured by flow cytometry. G-LISA was used to measure Ras inactivation. Western blot was used to measure AKT and ERK activation. MIA PaCa-2 cells implanted subcutaneously into nude mice were treated with D14 or C22 and tumor volumes were recorded. Results According to the binding affinity estimation, D14 and C22 stabilized the protein-protein interaction in the KRas4B-PDE6δ complex based on in vitro evaluation of the 38 compounds showing antineoplastic activity against pancreatic MIA PaCa-2 cancer cells. In this work, we further investigated the antineoplastic cellular properties of two of them, termed D14 and C22, which reduced the viability in the human pancreatic cancer cells lines MIA PaCa-2, PanC-1 and BxPC-3, but not in the normal pancreatic cell line hTERT-HPNE. Compounds D14 and C22 induced cellular death via apoptosis. D14 and C22 significantly decreased Ras-GTP activity by 33% in MIA PaCa-2 cells. Moreover, D14 decreased AKT phosphorylation by 70% and ERK phosphorylation by 51%, while compound C22 reduced AKT phosphorylation by 60% and ERK phosphorylation by 36%. In addition, compounds C22 and D14 significantly reduced tumor growth by 88.6 and 65.9%, respectively, in a mouse xenograft model. Conclusions We identified two promising compounds, D14 and C22, that might be useful as therapeutic drugs for pancreatic ductal adenocarcinoma treatment. Electronic supplementary material The online version of this article (10.1186/s12885-018-5142-7) contains supplementary material, which is available to authorized users.

Post‐translational modifications of histone H3 N‐terminal tails are key epigenetic regulators of virulence gene expression and sexual commitment in the human malaria parasite Plasmodium falciparum. Here, we identify proteolytic clipping of the N‐terminal tail of nucleosome‐associated histone H3 at amino acid position 21 as a new chromatin modification. A cathepsin C‐like proteolytic clipping activity is observed in nuclear parasite extracts. Notably, an ectopically expressed version of clipped histone H3, PfH3p‐HA, is targeted to the nucleus and integrates into mononucleosomes. Furthermore, chromatin immunoprecipitation and next‐generation sequencing analysis identified PfH3p‐HA as being highly enriched in the upstream region of six genes that play a key role in DNA replication and repair: In these genes, PfH3p‐HA demarcates a specific 1.5 kb chromatin island adjacent to the open reading frame. Our results indicate that, in P. falciparum, the process of histone clipping may precede chromatin integration hinting at preferential targeting of pre‐assembled PfH3p‐containing nucleosomes to specific genomic regions. The discovery of a protease‐directed mode of chromatin organization in P. falciparum opens up new avenues to develop new anti‐malarials.

The aim of this systematic review is to evaluate whether use of local or systemic antimicrobials would improve clinical results of non‐surgical periodontal therapy for smokers with chronic periodontitis (CP). Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, and The Cochrane Central Register of Controlled Trials were searched up to and including March 2016. Randomized clinical trials of duration of at least 6 months were included if they reported on treatment of smokers (≥10 cigarettes per day for minimum 12 months) with CP with non‐surgical periodontal therapy either alone or associated with local or systemic antimicrobials. Random‐effects meta‐analyses were undertaken to evaluate mean differences in probing depth (PD) and clinical attachment level (CAL). Of 108 potentially eligible articles, seven were included. Most individual studies (75%) testing locally delivered antibiotics reported that smokers benefited from this treatment approach. Pooled estimates found additional PD reduction of 0.81 mm (P = 0.01) and CAL gain of 0.91 mm (P = 0.01) at sites with baseline PD ≥5 mm. Conversely, meta‐analysis on systemic use of antimicrobials failed to detect significant differences in mean changes from baseline, and only one trial supported their use. In smokers with CP, adjunctive use of local antimicrobials improved efficacy of non‐surgical periodontal therapy in reducing PD and improving CAL at sites presenting PD ≥5 mm before treatment. Current evidence does not demonstrate similar gains when scaling and root planing plus systemic antimicrobial/antibiotics were associated with therapy.

In Latin America, public health systems that manage and warrant the health of the population lack mechanisms and technological capabilities that enable them to accept and adopt initiatives focused to guide, look after, and improve the quality of life of millions of patients with diabetes who need attention and special care. However, the proposal presented here for a holistic, interactive, and persuasive model to facilitate self-care of diabetes patients (hiPAPD) is the first proposal in Panama, Central America, and the Caribbean Region to develop and implement information communications technology (ICT) platforms for the care of patients with chronic diseases such as diabetes.The process of experimentation was initiated with an agreement with all the staff of the project to comply with the international biomedical studies stipulations, having as reference the Declaration of Helsinki of the World Medical Association (Recommendations to Guide to Doctors in Biomedical Research on People).After several months of evaluation and ongoing work the study obtained successful validation of the hiPAPD model. The project had the support of 107 patients with diabetes, their families, friends, doctors, nurses and nursing assistants, and social groups in rural communities. Finally, the project contributed to society with a highly innovative ICT environment that facilitates self-care of diabetes patients without financial resources and health.A timely health treatment at a decisive moment may be the difference in care for patients. Through the validation process conducted in this research initiative, it was demonstrated that the hiPAPD model, from the perspective of the patient with diabetes, relatives, friends, health workforce (nurses and nursing assistants), doctors, and societal contexts, allowed the improvement of the quality of life of patients with diabetes in poor rural zones of Panama.

The inverse relationship between early life and adult socioeconomic measures and mortality risk has been well established in developed countries, but remains practically unexplored in Latin American societies. The setting was Chile; the study included 11,600 adults living in the urban center of San Francisco de Mostazal. This was a prospective cohort study of a weighted random sample of 795 subjects followed up during 8 years.Education (elementary, high school and college), height (percentiles 50 and 75), and income (population quartiles) were assessed at baseline. Relative risks of all-cause mortality were computed in Cox regression models adjusting for age, gender, body mass index, smoking status, and joint effects of the socioeconomic measures.A graded inverse relationship with all-cause mortality was observed for education (risk: 1.0, 0.67, and 0.30, p for trend0.01) and height (risk: 1.0, 0.75, and 0.56, p for trend0.01), but not for income (p for trend = 0.94).These findings suggest a 'pauper rich' paradox in transitioning Latin American economies. Income level does not seem sufficient to improve survival in cohorts exposed to adverse early life influences reflected by education and height.

In Entamoeba histolytica little is known about the microfilament rearrangements formed by actin and ABPs. Fibronectin regulates many aspects of cell behavior involving the actin cytoskeleton and members of the Rho family of small GTPases. Using trophozoites interacted with fibronectin and glass, we present evidence related with the formation and regulation of different microfilament rearrangements and their cellular distribution, the effect of actin affecting drugs on these arrangements, and on trophozoites adhesion; we also demonstrate that actin isoforms are induced after adhesion, and also the selective participation of specific actin binding proteins such as ABP-120 and phospho-paxillin, regarding their location in the different actin structures. In addition, we show results that confirm the participation of EhRho, ROCK-2, and GAP activities. We propose that fibronectin induced signaling in E. histolytica trophozoites have important consequences in the actin cytoskeleton that may affect its behavior during the invasive process in the host.

RhoGDI proteins have been implicated in several human cancers; changes in their expression levels have shown pro- or anti-tumorigenic effects. Pancreatic Ductal Adenocarcinoma (PDAC) is a complex pathology, with poor prognosis, and most patients die shortly after diagnosis. Efforts have been focused on understanding the role of RhoGDI's in PDAC, specially, RhoGDI1 and RhoGDI2. However, the role of RhoGDI3 has not been studied in relation to cancer or to PDAC. Here, we characterized the expression and functionality of RhoGDI3 and its target GTPases, RhoG and RhoB in pancreatic cell lines from both normal pancreatic tissue and tissue in late stages of PDAC, and compared them to human biopsies. Through immunofluorescences, pulldown assays and subcellular fractionation, we found a reduction in RhoGDI3 expression in the late stages of PDAC, and this reduction correlates with tumor progression and aggressiveness. Despite the reduction in the expression of RhoGDI3 in PDAC, we found that RhoB was underexpressed while RhoG was overexpressed, suggesting that cancerous cells preserve their capacity to activate this pathway, thus these cells may be more eager to response to the stimuli needed to proliferate and become invasive unlike normal cells. Surprisingly, we found nuclear localization of RhoGDI3 in non-cancerous pancreatic cell line and normal pancreatic tissue biopsies, which could open the possibility of novel nuclear functions for this protein, impacting gene expression regulation and cellular homeostasis.

Background In human hosts, Entamoeba histolytica cysts can develop into trophozoites, suggesting that the life cycle of this parasite are regulated by changes in gene expression. To date, some evidence has suggested that epigenetic mechanisms such as DNA methylation and histone modification are involved in the regulation of gene expression in Entamoeba. Some post–translational modifications (PTMs) at the N-terminus of E. histolytica’s histones have been reported experimentally, including tri-methylation in the lysine 4 of histone H3 (H3K4me3) and dimethylation in the lysine 27 of histone H3 (H3K27me2), dimethylation of arginine 3 (H4R3me2) and the indirect acetylation of histone H4 in the N-terminal region. However, it is not known which residues of histone H4 are subject to acetylation and/or methylation or where in the nucleus these epigenetic marks are located. Methods Histones from trophozoites of E. histolytica were obtained and analyzed by LC-MS/MS. WB assays were performed using antibodies against epigenetic marks (acetylated lysines and methylated arginines). Immunofluorescence assays (IFA) were carried out to determine the distribution of PTMs and the localization of DNA methylation as a heterochromatin marker. Nuclear bodies such as the nucleolus were identified by using antibodies against fibrillarin and nucleolin and speckles by using anti-PRP6 antibody. Results Some new PTMs in histone H4 of E. histolytica, such as the acetylation of lysines 5, 8, 12 and 16 and the monomethylation of arginine 3, were identified by WB. IFA demonstrated that some marks are associated with transcriptional activity (such as acetylation and/or methylation) and that these marks are distributed throughout the E. histolytica nucleus. Staining with antibodies against anti-pan-acetylated lysine H4 histone and 5-methyl cytosine showed that the activation and transcriptional repression marks converge. Additionally, two nuclear bodies, the nucleolus and speckles, were identified in this parasite. Conclusions This study provides the first evidence that the nucleus of E. histolytica is not compartmentalized and contains two nuclear bodies, the nucleolus and speckles, the latter of which was not identified previously. The challenge is now to understand how these epigenetic marks and nuclear bodies work together to regulate gene expression in E. histolytica. Electronic supplementary material The online version of this article (doi:10.1186/s13071-016-1298-7) contains supplementary material, which is available to authorized users.

Small GTPases are signalling molecules that regulate important cellular processes. GTPases are deactivated by GTPase-activating proteins (GAPs). While human GAPs have been intensively studied, no GAP has yet been characterized in Entamoeba histolytica. In this study, we identified and characterized a novel nucleocytoplasmic RhoGAP in E. histolytica termed EhRhoGAPnc. In silico analyses of the domain structure revealed a previously undescribed peptide region within the carboxy-terminal region of EhRhoGAPnc capable of interacting with phosphatidic acid and phosphatidylinositol 3,5-bisphosphate. The full structural GAP domain showed increase GAP activity compared with the minimum region able to display GAP activity, as analysed both by experimental assays and molecular dynamics simulations. Furthermore, we identified amino acid residues that promote interactions between EhRhoGAPnc and its target GTPases EhRacC and EhRacD. Immunofluorescence studies revealed that EhRhoGAPnc colocalized with EhRacC and EhRacD during uroid formation but not during erythrophagocytosis. Interestingly, during erythrophagocytosis of red blood cells, EhRhoGAPnc colocalized with phosphatidic acid and phosphatidylinositol 3,5-bisphosphate. Overexpression of EhRhoGAPnc in E. histolytica led to inhibition of actin adhesion plate formation, migration, adhesion of E. histolytica to MDCK cells and consequently to an impairment of the cytopathic activity.

Although Plasmodium vivax is increasingly recognized as an important cause of morbidity in pregnancy in low malaria-transmission areas of Asia, little is know about the epidemiologic and clinical profiles of P. vivax in pregnant women in Latin America. We describe the clinical features and pregnancy outcomes in a series of 12 cases of P. vivax malaria in pregnant women complicated in some by miscarriage or preterm deliveries and in others with significant degrees of anemia and thrombocytopenia in a population where P. vivax is endemic in northeastern Venezuela.

Health indicators express remarkable gaps between health systems at a world-wide level. Countries of the entire world are overflowed by the need of new strategies, methodologies and technologies to better serve the millions of patients, who demand better medical attention. The present archaic and ephemerally systematized systems widen the gap even more than the quality of medical services that should be provided for the millions of diabetic patients. It is therefore necessary to develop highly familiar environments with diabetic patients and their care needs. A Holistic, Interactive and Persuasive ICT model to facilitate self care of patients with diabetes (hIPAPD), is proposed as an innovative technological development in Panama to health optimized treatment for diabetic patients. Three health centers located in the District of Aguadulce, Province of Cocle, located on Panama's Pacific Coast, were selected to validate the model; the area presents extremely poor population, mostly with one daily meal, without any health insurance and with a high illiteracy rate. A series of experiences in the application and validation process are presented and analyzed in order to confirm the application, value and contribution of ICTs in health care in poor regions of Central America.

Telomeres have the capacity to recruit proteins that facilitate the spreading of heterochromatin into subtelomeric DNA regions. In the human protozoan pathogen Plasmodium falciparum, the telomere-associated protein Sir2 has been shown to control the silencing of members of virulence genes at some, but not all, chromosome-end loci, indicating that additional proteins are involved in telomere position effect. Here, we identified, in P. falciparum, a novel telomere-associated protein that displays homology with the origin-of-recognition-complex 1 protein Orc1. Antibodies raised against this P. falciparum protein localized to telomeric clusters in the nuclear periphery and the nucleolus. It was found that, prior to DNA replication, P. falciparum Orc1 and Sir2 undergo drastic subcellular reorganization, such as dissociation from the telomere cluster and spreading into the nucleus and parasite cytoplasm. Relocation of Orc1 and Sir2 was also linked to the partial dissociation of telomere clusters. Super gel-shift and chromatin-immunoprecipitation experiments showed the physical association of Orc1 with telomere repeats but revealed a differential association with adjacent non-coding repeat DNA elements. Our data suggest that Plasmodium telomeres might fold back and that Orc1 cooperates with Sir2 in telomeric silencing.

We have cultured under monoxenic conditions and characterized an Entamoeba histolytica clone, MAV-I CINVESTAV (MAV-I), obtained from feces from an asymptomatic carrier. The clone shows the non-pathogenic E. histolytica zymodeme type I, which did not change through the process of monoxenization. Clone MAV-I was non-pathogenic in both in vivo and in vitro tests, and it did not have a functional 112-kDa adhesin. As far as we know, this is the first non-pathogenic monoxenic strain reported. Clone A (strain HM1:IMSS), a highly virulent clone with pathogenic zymodeme type II, and which has the 112-kDa adhesin, was used as a control. Protein patterns from both clones were almost identical in one-dimensional gels. In two-dimensional gels, differences in high-molecular-weight proteins were detected. Clone MAV-I adhered and phagocytosed only 12% of the red blood cells adhered and phagocytosed by clone A. MAV-I trophozoites did not destroy cell culture monolayers and did not produce hepatic abscesses in hamsters. They also showed deficiency in protease activity. The absence of virulence in clone MAV-I correlated directly with the absence of a functional 112-kDa adhesion, supporting the role that this protein plays in virulence.

It has been recently reported that the standard threefold conversion from haematocrit to haemoglobin underestimates the prevalence of anaemia and low levels of haemoglobin in children living in areas endemic for Plasmodium falciparum malaria. The data presented herein describes the experience in a malaria-endemic zone in northeastern Venezuela (state of Sucre), where a similar bias between haematocrit and haemoglobin in patients with Plasmodium vivax infection was found. In summary, the relationship between haematocrit and haemoglobin needs to be specifically evaluated according to each particular region or epidemiological setting.

Prevention of malaria in pregnant women is an utmost priority because the disease can cause serious maternal and neonatal complications. Maternal complications include marked anemia, increased risk of severe disease, and mortality, while the fetus or neonate is at risk of prematurity, anemia, and low birthweight. Pregnant women living in malaria endemic areas may be semiimmune to a particular Plasmodium spp. but when traveling to other regions, sometimes within their same country, where malaria epidemiology is different, may develop severe malaria complications. Here, we describe our experience in northeastern Venezuela associated with unfavorable outcomes of imported malaria cases among pregnant women who traveled to other Venezuelan regions with different malaria epidemiology. Travel medicine practitioners should be aware and educate their pregnant patients regarding the risk of malaria even when living in malaria endemic areas and traveling to other endemic areas such as occurs in Venezuela.

Dbl proteins are a family of factors that exchange the guanine nucleotide which promote the activation of Rho small GTPases. This paper reports the molecular, structural, biochemical and functional characterization of EhGEF2, a new member of the Dbl family. EhGEF2 is the second GEF studied in parasites and in the protozoan Entamoeba histolytica, and it is also the first member of the Dbl family that was found to have Arm repeats. The catalytic domain (DH) of EhGEF2 has the conserved residues T421, N590 and E591, which are important for the activation of the GTPases. Biochemical studies on EhGEF2 showed that it could activate in vitro the amoebic GTPases EhRacA, EhRacB, EhRacC, EhRacD, EhRacG, EhRacH and EhCdc42, being EhRacG its main target. It was found that the DH domain binds specifically phosphatidic acid (PA); docking and lipid dot blot studies indicated that this binding does not interfere with the contact surface of EhRacG. Functional studies showed that both the Arm repeats and the catalytic domain of EhGEF2 participate in its localization at the amoebic membrane. Expression of a negative dominant version of EhGEF2 protein in E. histolytica provoked a 30% decrease in its ability to phagocyte human erythrocytes as well as severe effects on both the proliferation and the cellular chemotaxis which suggest that EhGEF2 participates in these cellular processes.

The complete amino acid sequence of the Entamoeba histolytica unconventional myosin IB (Eh-myosin IB) is reported. Sequencing of overlapping cDNA fragments reveals a single open reading frame which predicts a 130 kDa protein of 1049 aa. Eh-myosin IB presents the three characteristic domains of myosins I subclass 1. This protein presents homology with myosins IB from other amoebae, but striking homologies with vertebrate unconventional myosins were also observed. The predicted actin and ATP-binding sites are located in the head domain. The heavy chain phosphorylation region is homologous to metazoan myosins I with an acidic residue present at the phosphorylation site. In the neck domain, an IQ motif indicates potential binding of calmodulin to the myosin I heavy chain. In the tail of Eh-myosin IB the three characteristic regions of myosin I are found. A putative membrane binding domain, a very short domain rich in alanine and proline we demonstrate to be functional for actin binding, and the src-homology 3 domain. The Entamoeba histolytica myosin IB is the first unconventional myosin so far described in a lower eukaryote.

Angiodysplasia of the colon as a cause of lower intestinal bleeding is diagnosed frequently in the elderly, with defined clinical characteristics. In the pediatric population there is little experience; only six cases have been reported. The present study evaluates the clinical, radiological, and surgical aspects of nine children with angiodysplasia of the colon who were treated at the National Institute of Pediatrics in Mexico City between 1970 and 1993. The mean age of clinical onset was 2.3 years. In six patients, symptoms appeared before the first year of life. Lower intestinal bleeding and severe anemia were present in all cases. The diagnosis and localization of the lesions were established by selective visceral angiography. Six patients were treated by operative resection of the affected colonic segments. For four patients with lesions in the rectum and sigmoid, a Swenson pullthrough was performed. In one patient the lesion was recurrent because of incomplete resection. Follow-up ranges from 8 months to 4 years; all patients have had normal hemoglobin levels and negative stool results. Unlike in the elderly and the cases reported in the literature, the left hemicolon was the most frequently involved area.

From 1985 to 1991, esophageal replacement was performed in seven patients with esophageal atresia without fistula. In four, the operation was performed in the neonatal period; three of these patients are alive. The other three patients were operated on between 2 and 3 months of age; two of them are alive. Six of the patients had colonic interposition, and the other had gastric interposition. Of the two patients who died, one had multiple associated malformations; the other one had a massive barium bronchoaspiration before the esophageal replacement.

Eight children with arteriovenous malformations of the gastrointestinal tract were studied during a two year period (1989-1993). The main localization of the arteriovenous malformations were: ascending colon (five cases), descending colon (five cases), terminal ileum (three cases), rectum and sigmoid (three cases). Diagnosis approach was made with colonoscopy and arteriography. Surgical resection of the affected segments was the therapeutical procedure in seven of the eight cases.

Fourteen children were treated for complications of severe colonic amebiasis. Seven had colon perforation; seven had toxic amoebic colitis. Those with perforation underwent colon resection limited to the perforation and adjacent abnormal colon. Those having toxic amoebic colitis without perforation were managed by temporary ileostomy. Vigorous general supportive treatment for endotoxic shock and amebiasis was given pre and postoperatively. Careful barium enema examinations proved safe and effective in diagnosis and follow-up. Ten patients survived (72%), five from each group.

A review of 30 children who had perforations of the bowel or gallbladder during a typhoid fever epidemic in Mexico City indicates that an excellent prognosis can be expected in children. The early diagnosis and aggressive management of hypovolemia is perhaps the most important factor. Bowel perforations were treated by a simple suture closure or resection in appropriate cases. There were innumerable postoperative complications, the most common being intraperitoneal abscess. In spite of the seriousness of the illness of these children and the frequency of postperforation complications, there was no operative mortality. The overall mortality was 3%.

Background All-trans retinoic acid (ATRA) is currently being used in clinical trials for cancer treatment. The use of ATRA is limited because some cancers, such as lung cancer, show resistance to treatment. However, little is known about the molecular mechanisms that regulate resistance to ATRA treatment. Akt is a kinase that plays a key role in cell survival and cell invasion. Akt is often activated in lung cancer, suggesting its participation in resistance to chemotherapy. In this study, we explored the hypothesis that activation of the Akt pathway promotes resistance to ATRA treatment at the inhibition of cell survival and invasion in lung cancer. We aimed to provide guidelines for the proper use of ATRA in clinical trials and to elucidate basic biological mechanisms of resistance. Results We performed experiments using the A549 human lung adenocarcinoma cell line. We found that ATRA treatment promotes PI3k-Akt pathway activation through transcription-independent mechanisms. Interestingly, ATRA treatment induces the translocation of RARα to the plasma membrane, where it colocalizes with Akt. Immunoprecipitation assays showed that ATRA promotes Akt activation mediated by RARα-Akt interaction. Activation of the PI3k-Akt pathway by ATRA promotes invasion through Rac-GTPase, whereas pretreatment with 15e (PI3k inhibitor) or over-expression of the inactive form of Akt blocks ATRA-induced invasion. We also found that treatment with ATRA induces cell survival, which is inhibited by 15e or over-expression of an inactive form of Akt, through a subsequent increase in the levels of the active form of caspase-3. Finally, we showed that over-expression of the active form of Akt significantly decreases expression levels of the tumor suppressors RARβ2 and p53. In contrast, over-expression of the inactive form of Akt restores RARβ2 expression in cells treated with ATRA, indicating that activation of the PI3k-Akt pathway inhibits the expression of ATRA target genes. Conclusion Our results demonstrate that rapid activation of Akt blocks transcription-dependent mechanism of ATRA, promotes invasion and cell survival and confers resistance to retinoic acid treatment in lung cancer cells. These findings provide an incentive for the design and clinical testing of treatment regimens that combine ATRA and PI3k inhibitors for lung cancer treatment.