Impacts of fire and prospects for recovery in a tropical peat forest ecosystem.

Uncontrolled fires place considerable burdens on forest ecosystems, compromising our ability to meet conservation and restoration goals. A poor understanding of the impacts of fire on ecosystems and their biodiversity exacerbates this challenge, particularly in tropical regions where few studies have applied consistent analytical techniques to examine a broad range of ecological impacts over multiyear time frames. We compiled 16 y of data on ecosystem properties (17 variables) and biodiversity (21 variables) from a tropical peatland in Indonesia to assess fire impacts and infer the potential for recovery. Burned forest experienced altered structural and microclimatic conditions, resulting in a proliferation of nonforest vegetation and erosion of forest ecosystem properties and biodiversity. Compared to unburned forest, habitat structure, tree density, and canopy cover deteriorated by 58 to 98%, while declines in species diversity and abundance were most pronounced for trees, damselflies, and butterflies, particularly for forest specialist species. Tracking ecosystem property and biodiversity datasets over time revealed most to be sensitive to recurrent high-intensity fires within the wider landscape. These megafires immediately compromised water quality and tree reproductive phenology, crashing commercially valuable fish populations within 3 mo and driving a gradual decline in threatened vertebrates over 9 mo. Burned forest remained structurally compromised long after a burn event, but vegetation showed some signs of recovery over a 12-y period. Our findings demonstrate that, if left uncontrolled, fire may be a pervasive threat to the ecological functioning of tropical forests, underscoring the importance of fire prevention and long-term restoration efforts, as exemplified in Indonesia.

Arrestin-3 scaffolding of the JNK3 cascade suggests a mechanism for signal amplification.

Scaffold proteins tether and orient components of a signaling cascade to facilitate signaling. Although much is known about how scaffolds colocalize signaling proteins, it is unclear whether scaffolds promote signal amplification. Here, we used arrestin-3, a scaffold of the ASK1-MKK4/7-JNK3 cascade, as a model to understand signal amplification by a scaffold protein. We found that arrestin-3 exhibited >15-fold higher affinity for inactive JNK3 than for active JNK3, and this change involved a shift in the binding site following JNK3 activation. We used systems biochemistry modeling and Bayesian inference to evaluate how the activation of upstream kinases contributed to JNK3 phosphorylation. Our combined experimental and computational approach suggested that the catalytic phosphorylation rate of JNK3 at Thr-221 by MKK7 is two orders of magnitude faster than the corresponding phosphorylation of Tyr-223 by MKK4 with or without arrestin-3. Finally, we showed that the release of activated JNK3 was critical for signal amplification. Collectively, our data suggest a "conveyor belt" mechanism for signal amplification by scaffold proteins. This mechanism informs on a long-standing mystery for how few upstream kinase molecules activate numerous downstream kinases to amplify signaling.

Signal execution modes emerge in biochemical reaction networks calibrated to experimental data.

Mathematical models of biomolecular networks are commonly used to study cellular processes; however, their usefulness to explain and predict dynamic behaviors is often questioned due to the unclear relationship between parameter uncertainty and network dynamics. In this work, we introduce PyDyNo (Python dynamic analysis of biochemical networks), a non-equilibrium reaction-flux based analysis to identify dominant reaction paths within a biochemical reaction network calibrated to experimental data. We first show, in a simplified apoptosis execution model, that despite the thousands of parameter vectors with equally good fits to experimental data, our framework identifies the dynamic differences between these parameter sets and outputs three dominant execution modes, which exhibit varying sensitivity to perturbations. We then apply our methodology to JAK2/STAT5 network in colony-forming unit-erythroid (CFU-E) cells and provide previously unrecognized mechanistic explanation for the survival responses of CFU-E cell population that would have been impossible to deduce with traditional protein-concentration based analyses.

Neurodevelopment in preschool children exposed and unexposed to Zika virus in utero in Nicaragua: a prospective cohort study.

BACKGROUND: Data on long-term neurodevelopmental outcomes of normocephalic children (born with normal head circumference) exposed to Zika virus in utero are scarce. We aimed to compare neurodevelopmental outcomes in normocephalic children up to age 48 months with and without Zika virus exposure in utero. METHODS: In this prospective cohort study, we included infants from two cohorts of normocephalic children born in León and Managua, Nicaragua during the 2016 Zika epidemic. In León, all women pregnant during the two enrolment periods were eligible. In Managua, mother-child pairs were included from three districts in the municipality of Managua: all women who became pregnant before June 15, 2016, and had a due date of Sept 15, 2016 or later were eligible. Infants were serologically classified as Zika virus-exposed or Zika virus-unexposed in utero and were followed up prospectively until age 48 months. At 36 months and 48 months of age, the Mullen Scales of Early Learning (MSEL) assessment was administered. Primary outcomes were MSEL early learning composite (ELC) scores at 30-48 months in León and 36-48 months in Managua. We used an inverse probability weighting generalised estimating equations model to assess the effect of Zika virus exposure on individual MSEL cognitive domain scores and ELC scores, adjusted for maternal education and age, poverty status, and infant sex. FINDINGS: The initial enrolment period for the León cohort was between Jan 31 and April 5, 2017 and the second was between Aug 30, 2017, and Feb 22, 2018. The enrolment period for the Managua cohort was between Oct 24, 2019, and May 5, 2020. 478 mothers (482 infants) from the León cohort and 615 mothers (609 infants) from the Managua cohort were enrolled, of whom 622 children (303 from the León cohort; 319 from the Managua cohort) were included in the final analysis; four children had microcephaly at birth and thus were excluded from analyses, two from each cohort. 33 (11%) of 303 children enrolled in León and 219 (69%) of 319 children enrolled in Managua were exposed to Zika virus in utero. In both cohorts, no significant differences were identified in adjusted mean ELC scores between Zika virus-exposed and unexposed infants at 36 months (between-group difference 1·2 points [95% CI -4·2 to 6·5] in the León cohort; 2·8 [-2·4 to 8·1] in the Managua cohort) or at 48 months (-0·9 [-10·8 to 8·8] in the León cohort; 0·1 [-5·1 to 5·2] in the Managua cohort). No differences in ELC scores between Zika virus-exposed and unexposed infants exceeded 6 points at any time between 30 months and 48 months in León or between 36 months and 48 months in Managua, which was considered clinically significant in other settings. INTERPRETATION: We found no significant differences in neurodevelopmental scores between normocephalic children with in-utero Zika virus exposure and Zika virus-unexposed children at age 36 months or 48 months. These findings are promising, supporting typical neurodevelopment in Zika virus-exposed normocephalic children, although additional follow-up and research is warranted. FUNDING: National Institute of Child Health and Development, National Institute of Allergy and Infectious Diseases, and Fogarty International Center. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Conventional Ameloblastoma. A Case Report with Microarray and Bioinformatic Analysis.

Ameloblastoma is a rare benign epithelial odontogenic neoplasm, but with great clinical implications, as despite its benignity and slow growth, most cases are locally aggressive with a significant recurrence rate. Histological, cellular, or molecular analyses of its pathogenesis have confirmed the complexity of this neoplasm. We present the case of a 20-year-old patient with a suggestive clinical and radiographic diagnosis of ameloblastoma. An incisional biopsy was obtained confirming the diagnosis of conventional ameloblastoma. Left hemimandibulectomy and plate reconstruction were performed. Histopathological analysis of the surgical specimen confirmed the conventional ameloblastoma with a plexiform pattern and significant areas of cystic degeneration and amyloid-like-like deposits. Additionally, a microarray was carried out with bioinformatic analysis for the enrichment, protein interaction, and determination of eight hub genes (CRP, BCHE, APP, AKT1, AGT, ACTC1, ADAM10, and APOA2) related to their pathogenesis.

Interactive Multiresolution Visualization of Cellular Network Processes.

Visualization plays a central role in the analysis of biochemical network models to identify patterns that arise from reaction dynamics and perform model exploratory analysis. To facilitate these analyses, we developed PyViPR, a visualization tool that generates static and dynamic representations of biochemical network processes within a Python-based environment. PyViPR embeds network visualizations within Jupyter notebooks, thus enabling integration with modeling, simulation, and analysis workflows. To present the capabilities of PyViPR, we explore execution mechanisms of extrinsic apoptosis in HeLa cells. We show that community-detection algorithms identify groups of molecular species that capture key biological functions and ease exploration of the apoptosis network. We then show how different kinetic parameter sets that fit the experimental data equally well exhibit significantly different signal-execution dynamics as the system progresses toward mitochondrial outer-membrane permeabilization. Therefore, PyViPR aids the conceptual understanding of dynamic network processes and accelerates hypothesis generation for further testing and validation.

Prevalence and seasonality of influenza-like illness in children, Nicaragua, 2005-2007.

Although information about seasonality and prevalence of influenza is crucial for development of effective prevention and control strategies, limited data exist on the epidemiology of influenza in tropical countries. To better understand influenza in Nicaragua, we performed a prospective 2-year cohort study of influenza-like illness (ILI) involving 4,276 children, 2-11 years of age, in Managua, during April 2005-April 2007. One peak of ILI activity occurred during 2005, in June-July; 2 peaks occurred during 2006, in June-July and November-December. The rate of ILI was 34.8/100 person-years. A household risk factor survey administered to a subset (61%) of participants identified the following risk factors: young age, asthma, and increasing person density in the household. Influenza virus circulation was confirmed during each ILI peak by laboratory testing of a subset of samples. Our findings demonstrate a high rate of ILI, with seasonal peaks, in children in Nicaragua.

The Nicaraguan pediatric dengue cohort study: study design, methods, use of information technology, and extension to other infectious diseases.

Dengue is a mosquito-borne viral disease that is a major public health problem worldwide. In 2004, the Pediatric Dengue Cohort Study was established in Managua, Nicaragua, to study the natural history and transmission of dengue in children. Here, the authors describe the study design, methods, and results from 2004 to 2008. Initially, 3,721 children 2-9 years of age were recruited through door-to-door visits. Each year, new children aged 2 years are enrolled in the study to maintain the age structure. Children are provided with medical care through the study, and data from each medical visit are recorded on systematic study forms. All participants presenting with suspected dengue or undifferentiated fever are tested for dengue by virologic, serologic, and molecular biologic assays. Yearly blood samples are collected to detect inapparent dengue virus infections. Numerous information and communications technologies are used to manage study data, track samples, and maintain quality control, including personal data assistants, barcodes, global information systems, and fingerprint scans. Close collaboration with the Nicaraguan Ministry of Health and use of almost entirely local staff are essential components for success. This study is providing critical data on the epidemiology and transmission of dengue in the Americas needed for future vaccine trials.

Quantitative assessment of the benefits of specific information technologies applied to clinical studies in developing countries.

Clinical studies and trials require accessibility of large amounts of high-quality information in a timely manner, often daily. The integrated application of information technologies can greatly improve quality control as well as facilitate compliance with established standards such as Good Clinical Practice (GCP) and Good Laboratory Practice (GLP). We have customized and implemented a number of information technologies, such as personal data assistants (PDAs), geographic information system (GIS), and barcode and fingerprint scanning, to streamline a pediatric dengue cohort study in Managua, Nicaragua. Quantitative data was obtained to assess the actual contribution of each technology in relation to processing time, accuracy, real-time access to data, savings in consumable materials, and time to proficiency in training sessions. In addition to specific advantages, these information technologies benefited not only the study itself but numerous routine clinical and laboratory processes in the health center and laboratories of the Nicaraguan Ministry of Health.

Fijadores externos para tratar fractura mandibular causada por herida de arma de fuego. Reporte de caso / External fxators as treatment for mandibular fracture caused by gunshot wound. Case report

Introducción: las heridas por proyectil de arma de fuego en la región craneofacial provocan daños funcionales devastadoras y deformidades estéticas, que se suman al trauma psicológico al momento del regreso a la vida cotidiana de un paciente. Por esta razón, la reconstrucción adecuada es esencial para una rehabilitación integral. La fijación externa es un método de reducción cerrada de fracturas que implica el uso de tornillos para manipular segmentos sueltos de hueso, que luego se fijan mediante conexiones externas. Es importante recalcar que las fracturas mandibulares causadas por proyectil de arma de fuego son un reto para este tipo de tratamiento. Objetivo: presentar el caso de un paciente con fractura mandibular por proyectil de arma de fuego tratado con fijadores externos y revisión de la literatura sobre este tipo de tratamiento. Caso clínico: paciente masculino de 19 años que presentó fractura de rama mandibular izquierda causado por proyectil de arma de fuego; la fractura se manejó mediante la colocación de fijación intermaxilar con arcos barra tipo Erich y fijación externa durante 3 meses. Como parte del resultado, el paciente presentó una correcta oclusión dentaria y mantiene sus movimientos mandibulares sin ninguna limitación. Esto demuestra que la reducción cerrada y fijación externa debe mantenerse en el arsenal terapéutico debido a sus adecuados resultados comprobados en la literatura y en este caso. Ahora bien, aunque la reducción abierta y fijación interna con material de osteosíntesis hace parte del manejo idóneo para todo tipo de fractura, todos los casos requieren ser individualizados.

Background: wounds from a frearm projectile in the craniofacial region cause devastating functional damage and aesthetic deformities, along with psychological trauma when returning to daily life. This is why proper reconstruction is essential for comprehensive rehabilitation. External fxation is a method of closed fracture reduction that involves the use of screws to manipulate loose segments of bone that are then fxed using external connections. Objective: to present the case of a patient with a mandibular fracture caused by a frearm projectile treated with external fixators and review the literature. Clinical case: a 19-year-old male patient who presented a fracture of the left mandibular ramus caused by a frearm projectile, the fracture was managed by placing intermaxillary fxation with Erich-type bar arches and external fixation for 3 months. The patient presented a correct dental occlusion and maintains his mandibular movements without any limitation. Conclusion: mandibular fractures caused by frearm projectiles are a challenge for treatment. Open reduction and internal fixation with osteosynthesis material is the ideal management for all types of fractures, however, all cases must be individualized, and it must be considered that closed reduction and external fxation must remain in our therapeutic arsenal due to their adequate results verifed in the literature and in our case.

[STAT3 activation by hypoxia in in vitro models of cervix cancer and endothelial cells].

INTRODUCTION: The biological behavior of cancer cells is influenced by the tumor microenvironment in which they develop. In this context, stressor stimuli such as hypoxia are considered critical for tumor development and therapeutic management. Cellular response to various stimuli is evidenced in the activation of intracellular signaling pathways such as JAK/STAT, which is one of the most important for its effects in differentiation and cell proliferation. OBJECTIVE: To evaluate the condition of the JAK/STAT pathway through the expression/activation of the STAT3 protein in cervix cancer cells (HeLa) and endothelial cells (EA.hy926) subjected to hypoxia. MATERIAL AND METHODS: Cell lines were subjected to physical (1% O2) or chemical (deferoxamine, DFO, 100 µM) hypoxia for 2, 6 and 24 hours. Changes in the expression and activation of STAT3, and its subcellular localization by indirect immunofluorescence, were determined by western blot. RESULTS: Hypoxia was evidenced by the activation and translocation to the nucleus of HIF-1. Neither physical nor chemical hypoxia altered STAT3 expression, but it did affect its activation, as seen in its phosphorylation and translocation to the nucleus in the two models under study. CONCLUSIONS: The present study highlights the importance of hypoxia as a stimulus that modifies the activation of the STAT3 protein in HeLa and EA.hy926 cells, which makes it an important factor in the design of therapeutic strategies against cancer.

Recomendaciones y consideraciones del Comité Vascular de la Asociación Colombiana de Neurología para el manejo del ataque cerebrovascular isquémico durante la pandemia por covid-19 / Considerations and recommendations from the Stroke Committee of the Colombian Neurological Association for the management of Acute Ischemic Stroke during the pandemic for COVID-19

RESUMEN PROPÓSITO: En marzo 11 del 2020 la Organización Mundial de la Salud declara la pandemia por Covid-19. El clínico se va enfrentar a pacientes con ataque cerebrovascular (ACV) y sospecha o presencia de la infección. Miembros participantes del comité vascular de la Asociación Colombiana de Neurología basados en la experticia y la literatura amplían las primeras recomendaciones en el manejo de los pacientes con ACV isquémico agudo durante la actual pandemia. MÉTODOS: Mediante reuniones virtuales y por consenso de los participantes se escogieron tres ejes de trabajo: Tamización para Covid-19, Medidas de bioseguridad y Aspectos relevantes del ACV isquémico en época de pandemia por Covid-19. Se desarrollaron los ejes por grupos de trabajo mediante la modalidad de pregunta-respuesta pretendiendo generar en cada una de ellas recomendaciones sobre el tema. La versión final del documento conto con la revisión y el aval de todos los participantes. RESULTADOS: El documento cuenta con tres secciones correspondientes a los ejes de trabajo. En el primer eje se responden 3 preguntas y se dan recomendaciones sobre la tamización de la infección por Covid-19 en ACV agudo. En el segundo se responden 8 preguntas y se dan recomendaciones sobre las medidas de bioseguridad en la atención de pacientes con ACV durante la pandemia. En el tercero se tratan 13 aspectos relevantes del ACV durante la pandemia, según criterio de los participantes, y se dan recomendaciones pertinentes. CONCLUSIÓN: Las recomendaciones son basadas en la literatura y consenso de los participantes para el cuidado de pacientes con ACV isquémico agudo con sospecha o infección por Covid-19. No pretenden reemplazar las guías o protocolos establecidos sino ampliar las primeras recomendaciones del comité y apoyar al clínico en la atención de pacientes con ACV isquémico durante la pandemia.

SUMMARY PURPOSE: The World Health Organization declared the COVID-19 pandemic on March 11th 2020. Clinicians will face patients with stroke and confirmed or suspected infection. Members of the Stroke Committee of the Colombian Neurological Association based on their expertise and literature review extend on the first recommendations on acute ischemic stroke management during the pandemic. METHODS: Through virtual meetings and by consensus of participants three topics were selected: COVID-19 screening, biosafety measures and relevant aspects of acute ischemic stroke care during the pandemic. A question and answer format was used to develop recommendations for each topic. RESULTS: The manuscript is divided into three sections. The first includes three questions and recommendations on screening for COVID-19 in stroke patients. The second includes 8 questions and recommendations on biosafety measures on stroke patients during the pandemic. The last section includes 13 relevant stroke topics during COVID-19 pandemic, as deemed by the authors, and their recommendations. CONCLUSIONS: Recommendations on stroke care and COVID-19 are based on literature review and expert consensus. The aim of the manuscript is to extend on the first recommendations forwarded by the Committee, not to replace current guidelines, and to support the clinician caring for stroke patients during the pandemic.

Activación de STAT3 por hipoxia en modelos in vitro de cáncer de cuello uterino y en células endoteliales / STAT3 activation by hypoxia in in vitro models of cervix cancer and endothelial cells

resumen Introducción: El microambiente tumoral influye en el comportamiento de las células cancerosas. Especialmente, el estímulo de agentes estresantes, como la hipoxia, se convierte en un factor crítico para la evolución y el tratamiento del cáncer. La reacción celular frente a diversos estímulos se manifiesta en la activación de vías de señalización como la JAK/STAT, una de las más importantes por sus efectos en la diferenciación y proliferación celular. Objetivo: Evaluar el estado de la vía JAK/STAT mediante la expresión o activación de la proteína STAT3 en células de cáncer de cuello uterino (HeLa) y en células endoteliales (EA.hy926) sometidas a hipoxia. Materiales y métodos: Las líneas celulares se sometieron a condiciones de hipoxia física (1 % de O2) o química (100 μM de deferoxamina, DFO) durante dos, seis y 24 horas. Mediante Western blot se determinó el cambio en la expresión y activación de STAT3, y mediante inmunofluorescencia indirecta su localización subcelular. Resultados:. La hipoxia se evidenció por la activación y translocación al núcleo del HIF-1. Ni la hipoxia física ni la química alteraron la expresión de STAT3, pero sí la activación, según se comprobó por su fosforilación y su translocación al núcleo en los dos modelos bajo estudio. Conclusiones: Se evidenció la importancia de la hipoxia como un estímulo que modifica la activación de la proteína STAT3 en las células HeLa y EA.hy926, lo cual la convierte en un elemento importante en el diseño de estrategias terapéuticas contra el cáncer.

Abstract Introduction: The biological behavior of cancer cells is influenced by the tumor microenvironment in which they develop. In this context, stressor stimuli such as hypoxia are considered critical for tumor development and therapeutic management. Cellular response to various stimuli is evidenced in the activation of intracellular signaling pathways such as JAK/STAT, which is one of the most important for its effects in differentiation and cell proliferation. Objective: To evaluate the condition of the JAK/STAT pathway through the expression/activation of the STAT3 protein in cervix cancer cells (HeLa) and endothelial cells (EA.hy926) subjected to ypoxia. Material and methods: Cell lines were subjected to physical (1% O2) or chemical (deferoxamine, DFO, 100 μM) hypoxia for 2, 6 and 24 hours. Changes in the expression and activation of STAT3, and its subcellular localization by indirect immunofluorescence, were determined by western blot. Results: Hypoxia was evidenced by the activation and translocation to the nucleus of HIF-1. Neither physical nor chemical hypoxia altered STAT3 expression, but it did affect its activation, as seen in its phosphorylation and translocation to the nucleus in the two models under study. Conclusions: The present study highlights the importance of hypoxia as a stimulus that modifies the activation of the STAT3 protein in HeLa and EA.hy926 cells, which makes it an important factor in the design of therapeutic strategies against cancer.

Early clinical features of dengue virus infection in nicaraguan children: a longitudinal analysis.

BACKGROUND: Tens of millions of dengue cases and approximately 500,000 life-threatening complications occur annually. New tools are needed to distinguish dengue from other febrile illnesses. In addition, the natural history of pediatric dengue early in illness in a community-based setting has not been well-defined. METHODS: Data from the multi-year, ongoing Pediatric Dengue Cohort Study of approximately 3,800 children aged 2-14 years in Managua, Nicaragua, were used to examine the frequency of clinical signs and symptoms by day of illness and to generate models for the association of signs and symptoms during the early phase of illness and over the entire course of illness with testing dengue-positive. Odds ratios (ORs) and 95% confidence intervals were calculated using generalized estimating equations (GEE) for repeated measures, adjusting for age and gender. RESULTS: One-fourth of children who tested dengue-positive did not meet the WHO case definition for suspected dengue. The frequency of signs and symptoms varied by day of illness, dengue status, and disease severity. Multivariable GEE models showed increased odds of testing dengue-positive associated with fever, headache, retro-orbital pain, myalgia, arthralgia, rash, petechiae, positive tourniquet test, vomiting, leukopenia, platelets ≤150,000 cells/mL, poor capillary refill, cold extremities and hypotension. Estimated ORs tended to be higher for signs and symptoms over the course of illness compared to the early phase of illness. CONCLUSIONS: Day-by-day analysis of clinical signs and symptoms together with longitudinal statistical analysis showed significant associations with testing dengue-positive and important differences during the early phase of illness compared to the entire course of illness. These findings stress the importance of considering day of illness when developing prediction algorithms for real-time clinical management.

Unusual dengue virus 3 epidemic in Nicaragua, 2009.

The four dengue virus serotypes (DENV1-4) cause the most prevalent mosquito-borne viral disease affecting humans worldwide. In 2009, Nicaragua experienced the largest dengue epidemic in over a decade, marked by unusual clinical presentation, as observed in two prospective studies of pediatric dengue in Managua. From August 2009-January 2010, 212 dengue cases were confirmed among 396 study participants at the National Pediatric Reference Hospital. In our parallel community-based cohort study, 170 dengue cases were recorded in 2009-10, compared to 13-65 cases in 2004-9. In both studies, significantly more patients experienced "compensated shock" (poor capillary refill plus cold extremities, tachycardia, tachypnea, and/or weak pulse) in 2009-10 than in previous years (42.5% [90/212] vs. 24.7% [82/332] in the hospital study (p<0.001) and 17% [29/170] vs. 2.2% [4/181] in the cohort study (p<0.001). Signs of poor peripheral perfusion presented significantly earlier (1-2 days) in 2009-10 than in previous years according to Kaplan-Meier survival analysis. In the hospital study, 19.8% of subjects were transferred to intensive care, compared to 7.1% in previous years - similar to the cohort study. DENV-3 predominated in 2008-9, 2009-10, and 2010-11, and full-length sequencing revealed no major genetic changes from 2008-9 to 2010-11. In 2008-9 and 2010-11, typical dengue was observed; only in 2009-10 was unusual presentation noted. Multivariate analysis revealed only "2009-10" as a significant risk factor for Dengue Fever with Compensated Shock. Interestingly, circulation of pandemic influenza A-H1N1 2009 in Managua was shifted such that it overlapped with the dengue epidemic. We hypothesize that prior influenza A H1N1 2009 infection may have modulated subsequent DENV infection, and initial results of an ongoing study suggest increased risk of shock among children with anti-H1N1-2009 antibodies. This study demonstrates that parameters other than serotype, viral genomic sequence, immune status, and sequence of serotypes can play a role in modulating dengue disease outcome.

Severe coinfections of dengue and pandemic influenza A H1N1 viruses.

Here we report on 4 hospitalized patients with dengue-influenza virus coinfections. All patients were RT-PCR positive for dengue virus and pandemic influenza A H1N1. Clinical findings at presentation ranged from influenza-like illness to severe dengue. Clinical progression of the infections varied, but all developed dengue symptoms and had interstitial infiltrates. Three cases required intensive care management and 1 case was fatal.

Index cluster study of dengue virus infection in Nicaragua.

Traditional study designs do not identify acute asymptomatic or pre-symptomatic dengue virus (DENV) infections, thus limiting our understanding of immunologic and viral factors that modulate infection outcome. In the 2006 and 2007 dengue seasons, we conducted a pilot index cluster study in Managua, Nicaragua, in which 442 persons living within 50 meters of 22 index cases identified through an ongoing pediatric cohort study were evaluated for DENV infection. Post-enrollment and pre-enrollment DENV infections were confirmed in 12 (2.7%) and 19 (4.3%) contacts, respectively. Five (42%) post-enrollment infections were asymptomatic, and DENV-2 was identified in 9 (75%) infections. Phylogenetic analysis with full-length DENV genomic sequence from contacts, index cases, and cohort dengue cases indicated focal transmission and infection outside the local area. We demonstrate the feasibility of identification of acute asymptomatic and pre-symptomatic cases in urban Latin America, the first report of such a study in the Americas, and identify age and concomitant immunity to DENV of contacts as a key factor in index cluster study design.

Molecular and physiological adaptation to prolonged drought stress in the leaves of two Andean potato genotypes.

Responses to prolonged drought and recovery from drought of two South American potato (Solanum tuberosum L. ssp. andigena (Juz & Buk) Hawkes) landraces, Sullu and Ccompis were compared under field conditions. Physiological and biomass measurements, yield analysis, the results of hybridisation to a potato microarray platform (44 000 probes) and metabolite profiling were used to characterise responses to water deficit. Drought affected shoot and root biomass negatively in Ccompis but not in Sullu, whereas both genotypes maintained tuber yield under water stress. Ccompis showed stronger reduction in maximum quantum yield under stress than Sullu, and less decrease in stomatal resistance. Genes associated with PSII functions were activated during recovery in Sullu only. Evidence for sucrose accumulation in Sullu only during maximum stress and recovery was observed, in addition to increases in cell wall biosynthesis. A depression in the abundance of plastid superoxide dismutase transcripts was observed under maximum stress in Ccompis. Both sucrose and the regulatory molecule trehalose accumulated in the leaves of Sullu only. In contrast, in Ccompis, the raffinose oligosaccharide family pathway was activated, whereas low levels of sucrose and minor stress-mediated changes in trehalose were observed. Proline, and expression of the associated genes, rose in both genotypes under drought, with a 3-fold higher increase in Sullu than in Ccompis. The results demonstrate the presence of distinct molecular and biochemical drought responses in the two potato landraces leading to yield maintenance but differential biomass accumulation in vegetative tissues.