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BACKGROUND: Childhood obesity is a multifactorial disease. Most of these factors start to develop before birth and worsen throughout life. Therefore, prevention efforts should begin in the first 1000 days of life. This study aimed to quantify published studies on risk factors according to the Six-Cs model of childhood obesity (cell, child, clan, culture, community, and country) and determine which of them have been related to anthropometric indicators of overweight or obesity in children under 2 years of age in Mexico. METHODS: A systematic scoping review (PRISMA-ScR) was performed. PubMed, Scopus, and EBSCOhost databases were reviewed. RESULTS: We found that 88% of the studies were observational. The child and family spheres were the most studied, individually and as a whole. The least studied were community, culture, and country. The main risk factors related to obesity indicators were high birth weight, birth by cesarean section, and inadequate feeding practices, in addition to mothers with obesity and those who underestimate their child's weight, stressful parenting style, and food insecurity in the home, together with living in urban areas, family income, and beliefs about preference for ultra-processed products. CONCLUSION: In Mexico, the study of obesity in early childhood is emerging at the research level. However, further efforts are required to close the knowledge gap at the socioecological level to design evidence-based interventions and reduce early obesity.

INTRODUCCIÓN: La obesidad infantil es una enfermedad multifactorial en la que varios factores comienzan a desarrollarse antes del nacimiento y se agravan a lo largo de la vida. Por ello, los esfuerzos de prevención para evitar su desarrollo deben comenzar durante los primeros 1000 días de vida. Los objetivos de este estudio fueron cuantificar los estudios publicados sobre factores de riesgo según el modelo de obesidad infantil de las 6-Cs (célula, niño, familia, cultura, comunidad y país) y determinar cuáles de ellos se han relacionado con indicadores de sobrepeso u obesidad en niños menores de 2 años en México. MÉTODOS: Se realizó una revisión sistemática de alcance (PRISMA-ScR). Se revisaron las bases de datos de PubMed, Scopus y EBSCOhost. RESULTADOS: Se encontró que el 88% de los estudios fueron de tipo observacional. La esfera niño y familia fueron las más abordadas, tanto individual como en conjunto. Las menos estudiadas fueron comunidad, cultura y país. Los principales factores de riesgo relacionados con indicadores de obesidad fueron alto peso al nacer, nacer por vía cesárea y prácticas inadecuadas de alimentación; además, madres con obesidad y que subestiman el peso del hijo, estilo de crianza presionante e inseguridad alimentaria en el hogar, aunado el vivir en zonas urbanas, ingreso económico-familiar y creencias sobre la preferencia por productos ultraprocesados. CONCLUSIONES: En México, el estudio de obesidad durante los primeros 1000 días es emergente a nivel de investigación, pero se requiere continuar con el esfuerzo para cerrar la brecha de conocimiento a nivel socio-ecológico, diseñar intervenciones basadas en la evidencia y disminuir la obesidad temprana.

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Abstract Background: Childhood obesity is a multifactorial disease. Most of these factors start to develop before birth and worsen throughout life. Therefore, prevention efforts should begin in the first 1000 days of life. This study aimed to quantify published studies on risk factors according to the Six-Cs model of childhood obesity (cell, child, clan, culture, community, and country) and determine which of them have been related to anthropometric indicators of overweight or obesity in children under 2 years of age in Mexico. Methods: A systematic scoping review (PRISMA-ScR) was performed. PubMed, Scopus, and EBSCOhost databases were reviewed. Results: We found that 88% of the studies were observational. The child and family spheres were the most studied, individually and as a whole. The least studied were community, culture, and country. The main risk factors related to obesity indicators were high birth weight, birth by cesarean section, and inadequate feeding practices, in addition to mothers with obesity and those who underestimate their child's weight, stressful parenting style, and food insecurity in the home, together with living in urban areas, family income, and beliefs about preference for ultra-processed products. Conclusion: In Mexico, the study of obesity in early childhood is emerging at the research level. However, further efforts are required to close the knowledge gap at the socioecological level to design evidence-based interventions and reduce early obesity.

Resumen Introducción: La obesidad infantil es una enfermedad multifactorial en la que varios factores comienzan a desarrollarse antes del nacimiento y se agravan a lo largo de la vida. Por ello, los esfuerzos de prevención para evitar su desarrollo deben comenzar durante los primeros 1000 días de vida. Los objetivos de este estudio fueron cuantificar los estudios publicados sobre factores de riesgo según el modelo de obesidad infantil de las 6-Cs (célula, niño, familia, cultura, comunidad y país) y determinar cuáles de ellos se han relacionado con indicadores de sobrepeso u obesidad en niños menores de 2 años en México. Métodos: Se realizó una revisión sistemática de alcance (PRISMA-ScR). Se revisaron las bases de datos de PubMed, Scopus y EBSCOhost. Resultados: Se encontró que el 88% de los estudios fueron de tipo observacional. La esfera niño y familia fueron las más abordadas, tanto individual como en conjunto. Las menos estudiadas fueron comunidad, cultura y país. Los principales factores de riesgo relacionados con indicadores de obesidad fueron alto peso al nacer, nacer por vía cesárea y prácticas inadecuadas de alimentación; además, madres con obesidad y que subestiman el peso del hijo, estilo de crianza presionante e inseguridad alimentaria en el hogar, aunado el vivir en zonas urbanas, ingreso económico-familiar y creencias sobre la preferencia por productos ultraprocesados. Conclusiones: En México, el estudio de obesidad durante los primeros 1000 días es emergente a nivel de investigación, pero se requiere continuar con el esfuerzo para cerrar la brecha de conocimiento a nivel socio-ecológico, diseñar intervenciones basadas en la evidencia y disminuir la obesidad temprana.

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Resumen Objetivo: México es uno de los países con mayor prevalencia de obesidad infantil a nivel mundial. Se requieren de instrumentos de valoración integrales válidos para el abordaje del problema. El Children Eating Behavior Questionnaire. (CEBQ) permite evaluar las conductas alimentarias de los niños relacionadas con el riesgo de obesidad, por lo que se planteó el siguiente objetivo evaluar las propiedades psicométricas de la versión original del CEBQ en niños mexicanos de 1 a 3 años. Material y Métodos: 201 madres residentes del noreste de México completaron el CEBQ en centros de salud comunitarios. Se realizó un análisis factorial confirmatorio (AFC) a través de componentes principales y fiabilidad (consistencia interna) con alfa de Cronbach (α). Resultados: Se identificó un modelo con siete factores y 24 ítems, los índices de bondad de ajuste del modelo propuesto fueron adecuados: índice de ajuste comparativo (CFI= 0.90), y error cuadrático medio de aproximación (RMSEA= 0.06). Los factores que integran el CEBQ tienen aceptable confiabilidad internaα > 0.70. Conclusión: El CEBQ en niños mexicanos de 1 a 3 años tiene propiedades psicométricas que lo hace una medida confiable y válida para evaluar comportamientos alimentarios relacionados con el riesgo de obesidad. Se recomienda contrastar este modelo en poblaciones similares.

Abstract Objective: Mexico is one of the countries with the highest prevalence of childhood obesity worldwide. Valid comprehensive assessment instruments are required to address the problem. The Child Eating Behavior Questionnaire(CEBQ) allows the assessment of children's eating behaviors related to obesity risk, so the following objective was to evaluate the psychometric properties of the original version of the CEBQ in Mexican children aged 1 to 3 years. Material and Methods: 201 mothers residing in northeastern Mexico completed the CEBQ in community health centers. A confirmatory factor analysis (CFA) was performed through principal components and reliability (internal consistency) with Cronbach's alpha (α). Results: A model with seven factors and 24 items was identified, the goodness-of-fit indices of the proposed model were adequate: comparative fit index (CFI=0.90), and root mean square error of approximation (RMSEA= 0.06). The factors that make up the CEBQ have acceptable internal reliability α > 0.70. Conclusion: The CEBQ in Mexican children aged 1 to 3 years has psychometric properties that make it a reliable and valid measure to assess eating behaviors related to obesity risk. It is recommended to contrast this model in similar populations.

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Water homeostasis is essential for fetal growth, and it depends on the successful development of the placenta. Many aquaporins (AQPs) were identified from blastocyst stages to term placenta. In the last years, cytokines, hormones, second messengers, intracellular pH, and membrane proteins were found to regulate their expression and function in the human placenta and fetal membranes. Accumulated data suggest that these proteins may be involved not only in the maintenance of the amniotic fluid volume homeostasis but also in the development of the placenta and fetal organs. In this sense, dysregulation of placental AQPs is associated with gestational disorders. Thus, current evidence shows that AQPs may collaborate in cellular events including trophoblast migration and apoptosis. In addition, aquaglyceroporins are involved in energy metabolism as well as urea elimination across the placenta. In the last year, the presence of AQP9 in trophoblast mitochondria opened new hypotheses about its role in pregnancy. However, much further work is needed to understand the importance of these proteins in human pregnancies.

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INTRODUCTION: Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection is characterised by a viral phase and a severe pro-inflammatory phase. The inhibition of the JAK/STAT pathway limits the pro-inflammatory state in moderate to severe COVID-19. METHODOLOGY: We analysed the data obtained by an observational cohort of patients with SARS-CoV-2 pneumonia treated with ruxolitinib in 22 hospitals of Mexico. The applied dose was determined based on physician's criteria. The benefit of ruxolitinib was evaluated using the 8-points ordinal scale developed by the NIH in the ACTT1 trial. Duration of hospital stay, changes in pro-inflammatory laboratory values, mortality, and toxicity were also measured. RESULTS: A total of 287 patients were reported at 22 sites in Mexico from March to June 2020; 80.8% received ruxolitinib 5 mg BID and 19.16% received ruxolitinib 10 mg BID plus standard of care. At beginning of treatment, 223 patients were on oxygen support and 59 on invasive ventilation. The percentage of patients on invasive ventilation was 53% in the 10 mg and 13% in the 5 mg cohort. A statistically significant improvement measured as a reduction by 2 points on the 8-point ordinal scale was described (baseline 5.39 ± 0.93, final 3.67± 2.98, p = 0.0001). There were 74 deaths. Serious adverse events were presented in 6.9% of the patients. CONCLUSIONS: Ruxolitinib appears to be safe in COVID-19 patients, with clinical benefits observed in terms of decrease in the 8-point ordinal scale and pro-inflammatory state. Further studies must be done to ensure efficacy against mortality.

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We recently reported that an intact caveolar structure is necessary for adequate cell migration and tubulogenesis of the human extravillous trophoblast (EVT) cells. Emerging evidence supports that hyperosmolarity induces the internalization of caveolae into the cytoplasm and accelerates their turnover. Furthermore, signaling pathways associated with the regulation of trophoblast differentiation are localized in caveolae. We hypothesized that hyperosmolarity impairs EVT differentiation and caveolae/caveolin-1 (Cav-1) participates in this process. EVT cells (Swan 71 cell line) were cultured in complete Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 and exposed to hyperosmolar condition (generated by the addition of 100 mM sucrose). Hyperosmolarity altered the EVT cell migration and the formation of tube-like structures. In addition, cell invasion was decreased along with a reduction in the latent and active forms of matrix metalloproteinase-2 (MMP-2) secreted by these cells. With respect to Cav-1 protein abundance, we found that hyperosmolarity enhanced its degradation by the lysosomal pathway. Accordingly, in the hyperosmolar condition, we also observed a significant increase in the number of vacuoles and the internalization of the caveolae into the cytoplasm. Taken together, our findings suggest that hyperosmolarity may induce caveolae internalization and increase their turnover, compromising the normal differentiation of EVT cells.

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We assessed the diagnostic utility of uric acid for the prediction of preeclampsia. An observational prospective approach was carried out during 2014. Preeclamptic women were classified into 4 groups accordingly to the onset of preeclampsia and the presence of intrauterine growth restriction (IUGR). Serum uric acid levels, urea, and creatinine were measured. Receiver operating curves (ROC) of the uric acid levels ratio (UAr) between a dosage before and after the 20th week of gestation were performed. One thousand two hundred and ninety-third pregnant women were enrolled in this study. Eight hundred ten had non-complicated pregnancies, 40 preeclampsia, 33 gestational hypertension, and 20 IUGR without preeclampsia. Uric acid significantly raised after 20 weeks of gestation in women who develop preeclampsia before 34 weeks (Group A) or in those who develop preeclampsia after 37 weeks associated with IUGR (Group C). In women who develop preeclampsia after 34 weeks without IUGR (Groups B and D), uric acid increased after the 30th week of gestation. In all groups, UAr was greater than 1.5. In gestational hypertension, UAr was superior to 1.5 toward the end of gestation, while in IUGR without preeclampsia, the behavior of serum uric acid was similar to non-complicated pregnancies. In all cases, urea and creatinine showed normal values, confirming that patients had no renal compromise. ROC area was 0.918 [95% confidence interval (CI): 0.858-0.979) for the preeclampsia group and 0.955 (95% CI: 0.908-1.000) for Group A. UAr at a cut-off point ≥1.5 had a very low positive predictive value, but a high negative predictive value of 99.5% for preeclampsia and it reached 100% for Group A. Thus, a UAr less than 1.5 may be a helpful parameter with a strong exclusion value and high sensitivity for those women who are not expected to develop preeclampsia. Additionally, this low-cost test would allow for better use of resources in developing countries.

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Caveolae constitute membrane domains critical for the organization and synchronization of different signaling molecules related to numerous cell processes such as cell migration, invasion, and differentiation. Caveolin-1 (Cav-1) is the main integral membrane protein of these domains. Recently, it was found that a normal expression of aquaporin-3 (AQP3) is required for extravillous trophoblast (EVT) cell migration. Our aim was to investigate the role of caveolae in the migration, invasion, and endovascular differentiation of human EVT cells during placentation and its interaction with AQP3. EVT cells (Swan 71 cell line) were cultured in complete Dulbecco's modified Eagle's medium-nutrient mixture F12 and treated with 5 mM methyl-ß-cyclodextrin (MßCD) to disrupt caveolae. We found that after MßCD treatment, Cav-1 protein was undetectable. In this condition, the ability of the cells to migrate was significantly decreased compared with the control cells, while no differences were observed in the number of invading cells and the metalloproteinases activity between control and MßCD-treated cells. Surprisingly, the disruption of caveolae significantly enhanced EVT endovascular differentiation. On the contrary, the silencing of AQP3, negatively affected tube-like formation. The theoretical analysis of the primary sequence of AQP3 protein revealed a putative Cav-1-binding site. In addition, immunoprecipitation and double immunofluorescence assays showed that AQP3 colocalized with Cav-1. These results showed that during placentation an intact caveola in EVT cells may be necessary for AQP3 and Cav-1 interaction and any perturbations might result in serious pregnancy disorders.

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In different tissues hyperosmolarity induces cell differentiation. Nevertheless an exacerbated hyperosmolar stress alters the normal cellular development. The transient receptor potential vanilloid 1 (TRPV-1) is a non-selective cation channel that is activated by hyperosmolarity and participates in many cellular processes. TPRV-1 is expressed in human placenta at term. Here, we evaluated the expression of TRPV-1 in first trimester extravillous trophoblast cells and its participation in the survival of these cells exposed to hyperosmolar stress. Our results showed that hyperosmolar stress up-regulates the expression of TRPV-1 and induces the apoptosis in Swan 71 cells. In addition, the inhibition of TRPV-1 abrogates the apoptotic events.

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Endocannabinoids are a group of endogenous lipid mediators that act as ligands of cannabinoid and vanilloid receptors, activating multiple signal transduction pathways. Together with enzymes responsible for their synthesis and degradation, these compounds constitute the endocannabinoid system (ECS), which is involved in different physiological processes in reproduction. The placenta, which is essential for the success of gestation and optimal fetal growth, undergoes constant tissue remodeling. ECS members are expressed in trophoblast cells, and current evidence suggests that this system is involved in placental development, apoptosis, and syncytialization. Impairment of endocannabinoid signaling has been associated with several pathological conditions such as intrauterine growth restriction and preeclampsia. Both clinical entities are characterized by dysregulation on vascular perfusion where nitrergic system performs a pivotal role. Nitric oxide (NO) is a potent local vasodepressor that exerts a critical role in the regulation of hemodynamic flow, contributing to the maintenance of low vascular resistance in the feto-placental circulation. NO production could be affected by different factors and growing evidence suggests that the endocannabinoid mediators may regulate nitrergic signaling. Herein, we review emerging knowledge supporting ECS-mediated regulation of NO production in normal placentation. Finally, we discuss how alterations in these systems could affect homoeostasis and contribute to the occurrence of placental-mediated pregnancy complications. Given the impact on women and perinatal heath, we will focus on current knowledge regarding the effects of ECS on nitrergic system in normal and pathological placentation.

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RESEARCH QUESTION: We recently reported that blocking of placental aquaporins (AQP) abrogates the apoptotic response of the trophoblast. As trophoblast apoptosis is exacerbated in pre-eclampsia, we hypothesized that changes in AQP in these placentae may trigger programmed cell death. We analysed AQP4 expression in pre-eclamptic placentae and its regulation by oxygen tension. DESIGN: AQP4 expression was studied in placentae from non-pathological and pre-eclamptic pregnancies by reverse transcription polymerase chain reaction (RT-PCR), Western blot, immunofluorescence and immunohistochemistry. Explants from non-pathological placentae were cultured in normoxia, hypoxia, hypoxia-reoxygenation and CoCl2. AQP4 expression was investigated by RT-PCR and Western blot. Hypoxia responsive elements sites on AQP4 promotor were investigated by in-silico analysis. AQP4 degradation was studied in the presence of proteosomal and lysosomal inhibitors. RESULTS: AQP4 protein expression was weakly detectable in pre-eclamptic placentae, but its mRNA was elevated compared with non-pathological placentae. In non-pathological explants cultured in hypoxia, AQP4 mRNA and protein were increased compared with placentae cultured in ambient oxygen but decreased after reoxygenation. Incubation with CoCl2, that stabilizes hypoxia inducible factor (HIF)-1α, also increased AQP4 levels. In-silico analysis showed three putative binding sites for HIF-1α in AQP4 promotor. CONCLUSIONS: Oxygen may regulate AQP4 expression in human placenta, possibly through HIF-1α. Therefore, the decrease in AQP4 throughout pregnancy, previously reported, is consistent with changes in HIF-1α, and suggests that AQP4 might have a crucial role during placentation. Therefore, the abnormal expression of AQP4 may be involved in the cause of pre-eclampsia, but it does not seem to take part in the apoptotic events.

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Accumulated evidence suggests that an abnormal placentation and an altered expression of a variety of trophoblast transporters are associated to preeclampsia. In this regard, an abnormal expression of AQP3 and AQP9 was reported in these placentas. Recent data suggests that placental AQPs are not only water channel proteins and that may participate in relevant processes required for a normal placental development, such as cell migration and apoptosis. Recently we reported that a normal expression of AQP3 is required for the migration of extravillous trophoblast (EVT) cells. Thus, alterations in this protein might lead to an insufficient transformation of the maternal spiral arteries resulting in fluctuations of oxygen tension, a potent stimulus for oxidative damage and trophoblast apoptosis. In this context, the increase of oxygen and nitrogen reactive species could nitrate AQP9, producing the accumulation of a non-functional protein affecting the survival of the villous trophoblast (VT). This may trigger the exacerbated release of apoptotic VT fragments into maternal circulation producing the systemic endothelial dysfunction underlying the maternal syndrome. Therefore, our hypothesis is that the alteration in the expression of placental AQPs observed at the end of gestation may take place during the trophoblast stem cell differentiation, disturbing both EVT and VT cells development, or during the VT differentiation and turnover. In both situations, VT is affected and at last the maternal vascular system is activated leading to the clinical manifestations of preeclampsia.

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Obesity is a metabolic disorder that predisposes to numerous diseases and has become a major global public health concern. Cafeteria diet (CAF) is the animal model used for the study of obesity that more closely reflects Western diet habits. Previously, we described that CAF administration for 60 days induces obesity in female rats and their fetuses develop macrosomia. Given that, in our model, rats are not genetically modified and that obese mothers were fed standard chow during pregnancy, the aim of the current study was to test the hypothesis that obesity alters the intrauterine environment prior to pregnancy, and this may explain the exacerbated fetal weight gain. We found that uteri from obese rats during the estrous phase developed insulin resistance through mechanisms that involve the induction of uterine hypoxia and the down-regulation of the insulin receptor gene. Moreover, uterine cell proliferation was induced by obesity concomitantly with the reduction in the uterine contractile response to a ß2 AR agonist, salbutamol, and this may be consequence of the down-regulation in the uterine ß2 AR expression. We conclude that CAF-induced obesity alters the uterine environment in rats during the estrous phase and may cause the fetal macrosomia previously described by us in obese animals. The lower sensitivity of the uterus to a relaxation stimulus (salbutamol) is not a minor fact given that for implantation to occur the uterus must be relaxed for embryo nidation. Thus, the alteration in the uterine quiescence may impair implantation and, consequently, the foregoing pregnancy.

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BACKGROUND: Web-based cognitive-behavioral interventions to reduce substance use can be a useful low-cost treatment for a large number of people, and an attractive option in countries where a greater availability of treatment is needed. OBJECTIVE: To evaluate the feasibility and initial effectiveness of a web-based cognitive-behavioral intervention for the reduction of substance use and depression compared with treatment as usual, with and without a printed self-help manual. METHOD: Individuals seeking outpatient treatment for substance use were randomly assigned to one of the following: (1) the web-based Help Program for Drug Abuse and Depression (n = 23); (2) an in-person session with an addiction therapist and use of the Alcohol, Smoking, and Substance Involvement Screening Test Self-Help Strategies guide, followed by treatment as usual (n = 25), or (3) treatment ordinarily offered in the participating treatment centers (n = 26). The study took place in 2013-2014 (trial registration: ISRCTN25429892), and participants completed baseline, posttreatment, and 1-month follow-up evaluation interviews. RESULTS: Treatment retention and data availability were comparable in all three conditions. A reduction was observed from baseline to follow-up in average days of use [F(1,28) = 29.70, p < 0.001], severity of use [F(2,28) = 143.66, p < 0.001], and depressive symptomatology [F = (4)16.40, p < 0.001], independent of the type of treatment provided. CONCLUSIONS: The findings suggest that the web-based intervention to reduce substance abuse is feasible, although it is not more effective than other intervention modalities; its effectiveness must be evaluated in a larger sample. Attrition was a main limitation; future studies must improve retention and assess cost-effectiveness.

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Preeclampsia is associated with histological alterations in the placenta. These alterations can be described by means of histological techniques. More specifically, immunohistochemistry could be used to detect proteins, and these in turn may be used to identify a specific cell type, to differentiate it from other cell types and to detect the expression of some markers deregulated in preeclampsia.This chapter focuses on the detection of specific cellular and molecular markers that evidence the alterations in the human placenta in preeclampsia.

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Pregnancy is a physiologically stressful condition that generates a series of functional adaptations by the cardiovascular system. The impact of pregnancy on this system persists from conception beyond birth. Recent evidence suggests that vascular changes associated with pregnancy complications, such as preeclampsia, affect the function of the maternal and offspring vascular systems, after delivery and into adult life. Since the vascular system contributes to systemic homeostasis, defective development or function of blood vessels predisposes both mother and infant to future risk for chronic disease. These alterations in later life range from fertility problems to alterations in the central nervous system or immune system, among others. It is important to note that rates of morbi-mortality due to pregnancy complications including preeclampsia, as well as cardiovascular diseases, have a higher incidence in Latin-American countries than in more developed countries. Nonetheless, there is a lack both in the amount and impact of research conducted in Latin America. An impact, although smaller, can be seen when research in vascular disorders related to problems during pregnancy is analyzed. Therefore, in this review, information about preeclampsia and endothelial dysfunction generated from research groups based in Latin-American countries will be highlighted. We relate the need, as present in many other countries in the world, for increased effective regional and international collaboration to generate new data specific to our region on this topic.

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Water homeostasis during fetal development is of crucial physiologic importance. The successful formation and development of the placenta is critical to maintain normal fetal growth and homeostasis. The expression of several aquaporins (AQPs ) was found from blastocyst stages to term placenta and fetal membranes. Therefore, AQPs are proposed to play important roles in normal pregnancy, fetal growth, and homeostasis of amniotic fluid volume, and water handling in other organs. However, the functional importance of AQPs in fetal development remains to be elucidated.

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BACKGROUND: Plasmodium vivax 48/45 protein is expressed on the surface of gametocytes/gametes and plays a key role in gamete fusion during fertilization. This protein was recently expressed in Escherichia coli host as a recombinant product that was highly immunogenic in mice and monkeys and induced antibodies with high transmission-blocking activity, suggesting its potential as a P. vivax transmission-blocking vaccine candidate. To determine sequence polymorphism of natural parasite isolates and its potential influence on the protein structure, all pvs48/45 sequences reported in databases from around the world as well as those from low-transmission settings of Latin America were compared. METHODS: Plasmodium vivax parasite isolates from malaria-endemic regions of Colombia, Brazil and Honduras (n = 60) were used to sequence the Pvs48/45 gene, and compared to those previously reported to GenBank and PlasmoDB (n = 222). Pvs48/45 gene haplotypes were analysed to determine the functional significance of genetic variation in protein structure and vaccine potential. RESULTS: Nine non-synonymous substitutions (E35K, Y196H, H211N, K250N, D335Y, E353Q, A376T, K390T, K418R) and three synonymous substitutions (I73, T149, C156) that define seven different haplotypes were found among the 282 isolates from nine countries when compared with the Sal I reference sequence. Nucleotide diversity (π) was 0.00173 for worldwide samples (range 0.00033-0.00216), resulting in relatively high diversity in Myanmar and Colombia, and low diversity in Mexico, Peru and South Korea. The two most frequent substitutions (E353Q: 41.9 %, K250N: 39.5 %) were predicted to be located in antigenic regions without affecting putative B cell epitopes or the tertiary protein structure. CONCLUSIONS: There is limited sequence polymorphism in pvs48/45 with noted geographical clustering among Asian and American isolates. The low genetic diversity of the protein does not influence the predicted antigenicity or protein structure and, therefore, supports its further development as transmission-blocking vaccine candidate.

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HDV infection may occur within a primary HBV infection (co-infection) or by sub sequent acquisition ofthe virus in patients with chronic hepatitis B (superinfection). Acute HDV infection is rarely diagnosed. Since cero conversion usually takes place about six weeks after viral infection, early diagnosis requires the use of direct diagnostic techniques, such as antigen HD V (HDAg) detection, or genomic amplification by means of molecular biology methods (RT-PCR). Here were port the case of a patient with chronic HBV infection that develops a severe acute hepatitis due to VHD superinfec- tion only detected by molecular biology.

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