The Flavonoid Isoquercitrin Precludes Initiation of Zika Virus Infection in Human Cells.

The medical importance of Zika virus (ZIKV) was fully highlighted during the recent epidemics in South Pacific islands and Americas due to ZIKV association with severe damage to fetal brain development and neurological complications in adult patients. A worldwide research effort has been undertaken to identify effective compounds to prevent or treat ZIKV infection. Fruits and vegetables may be sources of compounds with medicinal properties. Flavonoids are one class of plant compounds that emerge as promising antiviral molecules against ZIKV. In the present study, we demonstrated that flavonoid isoquercitrin exerts antiviral activity against African historical and Asian epidemic strains of ZIKV in human hepatoma, epithelial, and neuroblastoma cell lines. Time-of-drug addition assays showed that isoquercitrin acts on ZIKV entry by preventing the internalisation of virus particles into the host cell. Our data also suggest that the glycosylated moiety of isoquercitrin might play a role in the antiviral effect of the flavonoid against ZIKV. Our results highlight the importance of isoquercitrin as a promising natural antiviral compound to prevent ZIKV infection.

Recombinant Zika NS1 Protein Secreted from Vero Cells Is Efficient for Inducing Production of Immune Serum Directed against NS1 Dimer.

Zika virus (ZIKV) is a mosquito-borne flavivirus that recently emerged in the South Pacific, Americas, and Caribbean islands, where the larger epidemics were documented. ZIKV infection in humans is responsible for neurological disorders and microcephaly. Flavivirus NS1 is a non-structural glycoprotein that is expressed on the cell surface and secreted as a hexameric lipoprotein particle. Intracellular NS1 exists as a dimer that is required for viral replication, whereas the secreted NS1 hexamer interacts with host factors, leading to pathophysiological conditions. In an effort to dispose of specific anti-ZIKV NS1 immune serum, Vero cells were transduced with a lentiviral vector containing the NS1 gene from an epidemic strain of ZIKV. We showed that stably transduced Vero/ZIKV NS1 cell clone was efficient in the secretion of recombinant NS1 oligomer. Immunization of adult rat with purified extracellular NS1 developed anti-ZIKV antibodies that specifically react with the NS1 dimer produced in human cells infected with African and Asian strains of ZIKV. The rat antibody against ZIKV NS1 dimer is a reliable biological tool that enables the immunological detection of secreted NS1 from host-cells infected with ZIKV.

Complement-dependent virion lysis mediated by dengue-Zika virus cross-reactive antibodies correlates with protection from severe dengue disease.

Primary infection with one of four dengue virus serotypes (DENV1-4) may generate antibodies that protect or enhance subsequent secondary heterotypic infections. However, the characteristics of heterotypic cross-reactive antibodies associated with protection from symptomatic infection and severe disease are not well-defined. We selected plasma samples collected before a secondary DENV heterotypic infection that was classified either as dengue fever (DF, n = 31) or dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS, n = 33) from our longstanding pediatric cohort in Nicaragua. We screened various antibody properties to determine the features correlated with protection from DHF/DSS. Protection was associated with high levels of binding of various antibody isotypes, IgG subclasses and effector functions, including antibody-dependent complement deposition, ADCD. Although the samples were derived from DENV-exposed, Zika virus (ZIKV)-naïve individuals, the protective ADCD association was stronger when assays were conducted with recombinant ZIKV antigens. Further, we showed that a complement-mediated virion lysis (virolysis) assay conducted with ZIKV virions was strongly associated with protection, a finding reproduced in an independent sample set collected prior to secondary heterotypic inapparent versus symptomatic DENV infection. Virolysis was the main antibody feature correlated with protection from DHF/DSS and severe symptoms, such as thrombocytopenia, hemorrhagic manifestations, and plasma leakage. Hence, anti-DENV antibodies that cross-react with ZIKV, target virion-associated epitopes, and mediate complement-dependent virolysis are correlated with protection from secondary symptomatic DENV infection and DHF/DSS. These findings may support the rational design and evaluation of dengue vaccines and development of therapeutics.

Serotype-Specific Epidemiological Patterns of Inapparent versus Symptomatic Primary Dengue Virus Infections: A 17-year cohort study in Nicaragua.

Dengue is the most prevalent mosquito-borne viral disease and a major public health problem worldwide. Most primary infections with the four dengue virus serotypes (DENV1-4) are inapparent; nonetheless, whether the distribution of symptomatic versus inapparent infections by serotype varies remains unknown. Here, we present (1) the evaluation of a multiplex DENV1-4 envelope domain III multiplex microsphere-based assay (EDIII-MMBA) to serotype inapparent primary infections and (2) its application leveraging 17 years of prospective sample collection from the Nicaraguan Pediatric Dengue Cohort Study (PDCS). First, we evaluated the performance of the EDIII-MMBA with samples characterized by RT-PCR or focus reduction neutralization test. Next, we analyzed 46% (N=574) of total inapparent primary DENV infections in the PDCS with the EDIII-MMBA to evaluate the epidemiology of inapparent infections. Remaining infections were inferred using stochastic imputation, taking year and neighborhood into account. Infection incidence and percentage of inapparent, symptomatic, and severe infections were analyzed by serotype. The EDIII-MMBA demonstrated excellent overall accuracy (100%, 95.8-100%) for serotyping symptomatic and inapparent primary DENV infections when evaluated against gold-standard serotyping methods. We found that a significant majority of primary infections were inapparent, with DENV3 exhibiting the highest likelihood of symptomatic and severe primary infections (Pooled OR compared to DENV1 = 2.13, 95% CI 1.28-3.56, and 6.75, 2.01-22.62, respectively), whereas DENV2 was similar to DENV1 in both analyses. Significant within- and between-year variation in serotype distribution between symptomatic and inapparent infections and circulation of serotypes undetected in symptomatic cases were observed in multiple years. Our study indicates that case surveillance skews the perceived epidemiological footprint of DENV. We reveal a more complex and intricate pattern of serotype distribution in inapparent infections. The significant differences in infection outcomes by serotype emphasizes the need for vaccines with balanced immunogenicity and efficacy across serotypes.

Protection against symptomatic dengue infection by neutralizing antibodies varies by infection history and infecting serotype.

Dengue viruses (DENV1-4) are the most prevalent arboviruses in humans and a major public health concern. Understanding immune mechanisms that modulate DENV infection outcome is critical for vaccine development. Neutralizing antibodies (nAbs) are an essential component of the protective immune response, yet their measurement often relies on a single cellular substrate and partially mature virions, which does not capture the full breadth of neutralizing activity and may lead to biased estimations of nAb potency. Here, we analyze 125 samples collected after one or more DENV infections but prior to subsequent symptomatic or inapparent DENV1, DENV2, or DENV3 infections from a long-standing pediatric cohort study in Nicaragua. By assessing nAb responses using Vero cells with or without DC-SIGN and with mature or partially mature virions, we find that nAb potency and the protective NT50 cutoff are greatly influenced by cell substrate and virion maturation state. Additionally, the correlation between nAb titer and protection from disease depends on prior infection history and infecting serotype. Finally, we uncover variations in nAb composition that contribute to protection from symptomatic infection differently after primary and secondary prior infection. These findings have important implications for identifying antibody correlates of protection for vaccines and natural infections.

Primary exposure to Zika virus is linked with increased risk of symptomatic dengue virus infection with serotypes 2, 3, and 4, but not 1.

Infection with any of the four dengue virus serotypes (DENV1-4) can protect against or enhance subsequent dengue depending on preexisting antibodies and infecting serotype. Additionally, primary infection with the related flavivirus Zika virus (ZIKV) is associated with increased risk of DENV2 disease. Here, we measured how prior DENV and ZIKV immunity influenced risk of disease caused by DENV1-4 in a pediatric Nicaraguan cohort. Of 3412 participants in 2022, 10.6% experienced dengue cases caused by DENV1 (n = 139), DENV4 (n = 133), DENV3 (n = 54), DENV2 (n = 9), or an undetermined serotype (n = 39). Longitudinal clinical and serological data were used to define infection histories, and generalized linear and additive models adjusted for age, sex, time since last infection, and year, and repeat measurements were used to predict disease risk. Compared with flavivirus-naïve participants, primary ZIKV infection was associated with increased risk of disease caused by DENV4 (relative risk = 2.62, 95% confidence interval: 1.48 to 4.63) and DENV3 (2.90, 1.34 to 6.27), but not DENV1 infection. Primary DENV infection or DENV followed by ZIKV infection was also associated with increased risk of DENV4 disease. We reanalyzed 19 years of cohort data and demonstrated that prior flavivirus immunity and antibody titer had distinct associations with disease risk depending on incoming serotype. We thus find that prior ZIKV infection, like prior DENV infection, is associated with increased risk of disease with certain DENV serotypes. Cross-reactivity among flaviviruses should be considered when assessing vaccine safety and efficacy.

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.

Short forms of the postpartum depression screening scale: as accurate as the original form.

The aims of the present study were to develop three shorter forms of the Portuguese version of the Postpartum Depression Screening Scale (PDSS) as adapted and translated in Portugal, to analyse their psychometrics and to determine their cut-off points and associated conditional probabilities to screen for perinatal depression according to DSM-IV and ICD-10 criteria. In this study, 441 women in the third trimester of pregnancy and 453 in the third month of postpartum were interviewed for diagnostic purposes according to the Portuguese versions of the Diagnostic Interview for Genetic Studies and the Operational Criteria Checklist for Psychotic Illness. DSM-IV and ICD-10 classifications of depression were our gold standards for caseness. Three different shorter forms of the original Portuguese version of the PDSS were developed on the basis of reliability and factorial analysis. PDSS short versions, composed of seven and 21 (postpartum)/24 (pregnancy) items, presented significant reliability and validity and showed satisfactory combinations of sensitivity and specificity (≅80 %). The short forms of the original Portuguese version of the PDSS are valid alternatives to the 35-item version, given their equally precise screening performances, more concise structures and ease of completion.

The impact of physical activity on objective sleep of people with insomnia.

The aim of our study was to investigate if physical activity has a beneficial impact on insomnia. A systematic literature review was conducted in PubMed database using the terms "Physical activity" and "Insomnia" and 591 records were retrieved. The preferred reporting items for systematic reviews and meta-analyses guidelines were followed and fifteen articles were considered eligible for further analysis. Participants were mainly female, between 40 and 60 years; design studies were variable and most studies involved long-term interventions; insomnia definition was mainly based on diagnostic criteria or considered a specific cut-off point of well-known insomnia questionnaires; sleep was mostly assessed with polysomnography (PSG) or actigraphy; physical activity interventions included different methodologies (predominantly treadmill exercise). A beneficial effect of physical activity on insomnia was observed in most studies when sleep was evaluated with PSG or actigraphy. Sleep efficiency was the objective sleep parameter that mainly provided statistically significant results, as expected, followed by sleep onset latency, wake after sleep onset and, less frequently, total sleep time. Using objective methods to assess sleep in insomnia might be useful to support subjective insomnia complaints and to evaluate the efficacy of physical activity interventions in ameliorating sleep of people with insomnia.

Phylodynamics of dengue virus 2 in Nicaragua leading up to the 2019 epidemic reveals a role for lineage turnover.

BACKGROUND: Dengue is a mosquito-borne viral disease posing a significant threat to public health. Dengue virus (DENV) evolution is often characterized by lineage turnover, which, along with ecological and immunological factors, has been linked to changes in dengue phenotype affecting epidemic dynamics. Utilizing epidemiologic and virologic data from long-term population-based studies (the Nicaraguan Pediatric Dengue Cohort Study and Nicaraguan Dengue Hospital-based Study), we describe a lineage turnover of DENV serotype 2 (DENV-2) prior to a large dengue epidemic in 2019. Prior to this epidemic, Nicaragua had experienced relatively low levels of DENV transmission from 2014 to 2019, a period dominated by chikungunya in 2014/15 and Zika in 2016. RESULTS: Our phylogenetic analyses confirmed that all Nicaraguan DENV-2 isolates from 2018 to 2019 formed their own clade within the Nicaraguan lineage of the Asian/American genotype. The emergence of the new DENV-2 lineage reflects a replacement of the formerly dominant clade presiding from 2005 to 2009, a lineage turnover marked by several shared derived amino acid substitutions throughout the genome. To elucidate evolutionary drivers of lineage turnover, we performed selection pressure analysis and reconstructed the demographic history of DENV-2. We found evidence of adaptive evolution by natural selection at the codon level as well as in branch formation. CONCLUSIONS: The timing of its emergence, along with a statistical signal of adaptive evolution and distinctive amino acid substitutions, the latest in the NS5 gene, suggest that this lineage may have increased fitness relative to the prior dominant DENV-2 strains. This may have contributed to the intensity of the 2019 DENV-2 epidemic, in addition to previously identified immunological factors associated with pre-existing Zika virus immunity.

The association of neutralizing antibodies with protection against symptomatic dengue virus infection varies by serotype, prior infection history, and assay condition.

The four dengue virus serotypes (DENV1-4) are the most prevalent arboviruses in humans and a major public health concern worldwide. Understanding immune mechanisms that modulate DENV infection outcome is critical for epidemic preparedness and development of a safe and effective vaccine. Neutralizing antibodies (nAbs) are an essential component of the protective response, yet their measurement often relies on a single cellular substrate and partially mature virions, which do not capture the full breadth of neutralizing activity and may lead to biased estimations of nAb potency. Here, we investigated the characteristics of nAbs associated with protection against dengue cases using samples collected after one or more DENV infections but prior to subsequent symptomatic or inapparent DENV1, DENV2, or DENV3 infections from a long- standing pediatric cohort study in Nicaragua. By assessing nAb responses using Vero cells with or without the attachment factor DC-SIGN and with mature or partially mature virions, we found that nAb potency and the protective NT 50 cutoff were greatly influenced by cell substrate and virion maturation state. Additionally, the correlation between nAb titer and protection from disease depended on an individual's prior infection history and the subsequent infecting DENV serotype. Finally, we uncovered variations in nAbs composition that contributed to protection from symptomatic DENV infection differently after primary and secondary prior infection. These findings have important implications for identifying antibody correlates of protection in the context of vaccines and natural infections.

Primary exposure to Zika virus increases risk of symptomatic dengue virus infection with serotypes 2, 3, and 4 but not serotype 1.

Infection with any of the four dengue virus serotypes (DENV1-4) can protect against or enhance subsequent dengue depending on pre-existing antibodies and the subsequent infecting serotype. Additionally, primary infection with the related flavivirus Zika virus (ZIKV) has been shown to increase DENV2 disease. Here, we measured how prior DENV and ZIKV immunity influenced risk of disease caused by all four serotypes in a pediatric Nicaraguan cohort. Of 3,412 participants in 2022, 10.6% experienced symptomatic DENV infections caused by DENV1 (n=139), DENV4 (n=133), DENV3 (n=54), DENV2 (n=9), or an undetermined serotype (n=39). Longitudinal clinical and serological data were used to define infection histories, and generalized linear and additive models adjusted for age, sex, time since the last infection, cohort year, and repeat measurements were used to predict disease risk. Compared to flavivirus-naïve participants, primary ZIKV infection increased disease risk of DENV4 (relative risk = 2.62, 95% confidence interval: 1.48-4.63) and DENV3 (2.90, 1.34-6.27) but not DENV1 (1.20, 0.72-1.99). Primary DENV infection or a DENV followed by ZIKV infection also increased DENV4 risk. We re-analyzed 19 years of cohort data and demonstrated that prior flavivirus-immunity and pre-existing antibody titer differentially affected disease risk for incoming serotypes, increasing risk of DENV2 and DENV4, protecting against DENV1, and protecting at high titers but enhancing at low titers against DENV3. We thus find that prior ZIKV infection, like prior DENV infection, increases risk of certain DENV serotypes. Cross-reactivity among flaviviruses should be carefully considered when assessing vaccine safety and efficacy.

The role of perfectionism in postpartum depression and symptomatology.

The role of perfectionism as a correlate and as a predictor of perinatal depressive symptomatology and disorder was examined. Three-hundred and eighty-six pregnant women (mean age = 30.08 years; SD = 4.205; range = 19-44) completed the Portuguese versions of the Multidimensional Perfectionism Scale, Beck Depression Inventory-II/BDI-II and three questions evaluating anxiety trait, life stress and social support perception. Diagnoses of depression were obtained using the Portuguese version of the Diagnostic Interview for Genetic Studies/OPCRIT system. Women who were depressed in pregnancy (ICD-10/DSM-IV) were excluded from the analyses. Self-Oriented Perfectionism and Socially Prescribed Perfectionism subcomponents (Conditional Acceptance and Others' High Standards) were significant correlates of depressive symptomatology/BDI-II in pregnancy. Others' High Standards was a significant predictor of postpartum depressive symptomatology/BDI-II, after controlling the other independent variables (depressive symptomatology and trait anxiety in pregnancy, life stress and social support perception in postpartum). None of the perfectionism subscales predicted postpartum depressive disorder (ICD-10/DSM-IV). Self-Oriented Perfectionism was an important correlate of depressive symptomatology in pregnancy and Others' High Standards and Conditional Acceptance were significant correlates of perinatal depressive symptomatology. Others' High Standards accounted for 0.8 % of the depressive symptomatology variance in postpartum after controlling the effect for other depressive symptomatology correlates. Perfectionism was not a risk factor for postpartum depressive disorder. Our findings improve the knowledge regarding the risk factors implicated in the development of postpartum depressive symptomatology/disorder, which is of utmost importance to develop adequate prevention and intervention strategies.

Antibody Fc characteristics and effector functions correlate with protection from symptomatic dengue virus type 3 infection.

Preexisting cross-reactive antibodies have been implicated in both protection and pathogenesis during subsequent infections with different dengue virus (DENV) serotypes (DENV1-4). Nonetheless, humoral immune correlates and mechanisms of protection have remained elusive. Using a systems serology approach to evaluate humoral responses, we profiled plasma collected before inapparent or symptomatic secondary DENV3 infection from our pediatric cohort in Nicaragua. Children protected from symptomatic infections had more anti-envelope (E) and anti-nonstructural protein 1 (NS1) total immunoglobulin G (IgG), IgG4, and greater Fc effector functions than those with symptoms. Fc effector functions were also associated with protection from hemorrhagic manifestations in the pre-symptomatic group. Furthermore, in vitro virological assays using these plasma samples revealed that protection mediated by antibody-dependent complement deposition was associated with both lysis of virions and DENV-infected cells. These data suggest that E- and NS1-specific Fc functions may serve as correlates of protection, which can be potentially applied toward the design and evaluation of dengue vaccines.

Sleep disturbances, body mass index and eating behaviour in undergraduate students.

This study investigates the association between sleep disturbances, body mass index (BMI) and eating behaviour in a sample of undergraduate students. The sample comprises 870 medicine and dentistry students from Coimbra University (62.5% females), aged between 17 and 25 years. The Eating Attitudes Test-40 was used to measure eating behaviour, and two questions were applied addressing difficulties of initiating sleep (DIS) and difficulties of maintaining sleep (DMS). A sleep disturbance index (SDI) was calculated from the sum of DIS and DMS scores. Body mass index (BMI) was determined from self-reported weight and height. The correlation analyses generally indicated that global eating disturbance, bulimic behaviour dimension and social pressure to eat were associated particularly with sleep difficulties. An association between diet concerns and sleep difficulties was less consistent. Regression analyses showed that bulimic behaviour (BB) and social pressure to eat (SPE) dimensions were associated significantly with sleep difficulties (DIS, DMS, SDI) in the total sample (BB: from P<0.01 to P<0.001; SPE: P<0.05) and in males (BB: from P<0.05 to P<0.001; SPE: P<0.05) and with insomnia symptoms (P<0.01). In females, bulimic behaviour was the only factor associated significantly with sleep difficulties (SDI, DIS; P<0.01) and with insomnia symptoms (P<0.05). Although BMI was correlated negatively with sleep difficulties (P<0.05), regression analyses indicated that it was not associated significantly with them. Our findings support an association between eating behaviour and sleep disturbances in both genders, which may have treatment implications.

Is insomnia in late pregnancy a risk factor for postpartum depression/depressive symptomatology?

The aim of the present work was to investigate if insomnia in late pregnancy is a risk factor for postpartum depressive symptomatology/postpartum depression (PPD). 581 women in their last trimester of pregnancy answered questions/questionnaires about lifetime history of insomnia, current sleep perception, current mood and depressive symptomatology. They were interviewed with the Portuguese version of the Diagnostic Interview for Genetic Studies. After delivery 382 (65.7%) mothers participated again in the study. Insomnia in pregnancy was not a risk factor for PPD (DSM-IV or ICD-10) but was a significant predictor of postpartum depressive symptomatology. Negative Affect (NA) was a significant predictor of postpartum depressive symptomatology. Women with higher NA were 4.6 (CI95%=1.69-12.74) and 5.3 times (CI95%=2.26-12.58) more likely of experiencing PPD (DSM-IV/ICD-10, respectively) than women with lower NA. Lifetime Depression was a significant predictor of postpartum depressive symptomatology and ICD-10/PPD (OR=2.6; CI95%=1.16-4.38). Positive Affect (PA) showed to be a protective factor for postpartum depressive symptomatology and DSM-IV/PPD (OR=1.5; CI95%=1.20-2.33). Controlling NA, PA and Lifetime Depression, insomnia lost its predictive role, suggesting these variables might work as mediators. Associations between insomnia, NA, PA and Lifetime Depression should be assessed in pregnancy. This might help to preventively target NA, enhance PA and reduce the likelihood of experiencing postpartum depressive symptomatology.

The postpartum depression screening scale: is it valid to screen for antenatal depression?

The purpose of the study was to analyse for the first time the validity of a slightly modified version of the Portuguese Postpartum Depression Screening Scale (PDSS), to be used as a screening instrument for antenatal depression. Specifically, the aims were to analyse its psychometric properties, to determine PDSS cutoff points and associated conditional probabilities to screen for depression according to DSM-IV and ICD-10 criteria and to compare its screening performance with that of the Beck Depression Inventory-II (BDI-II). Five hundred and three pregnant women in the third trimester of pregnancy completed both questionnaires and were interviewed face-to-face with the Portuguese version of the Diagnostic Interview for Genetic Studies. The Portuguese version of the Operational Criteria Checklist for Psychotic Illness was used to obtain DSM-IV and ICD-10 diagnoses of depression, our gold standards for caseness. PDSS reliability and validity were very good and comparable to those obtained in the postpartum validation studies developed in Portugal and in other countries, showing satisfactory sensitivity and specificity combinations (≅80%). Compared with BDI-II, it has the advantage of being more specific for the motherhood context. Although developed for postpartum depression, PDSS is accurate to screen for antenatal depression, and it could be very useful for clinical and epidemiologic purposes.

Protective and enhancing interactions among dengue viruses 1-4 and Zika virus.

Dengue viruses 1-4 (DENV 1-4) and Zika virus (ZIKV) are closely related flaviviruses transmitted by Aedes mosquitoes that co-circulate in Asia, the Americas, Africa, and Oceania. Here, we review recent and historical literature on in vitro experiments, animal models, and clinical and epidemiological studies to describe how the sequence of DENV 1-4 and ZIKV infections modulates subsequent dengue and Zika disease outcome. Overall, we find these interactions are asymmetric. Immunity from a prior DENV infection or a prior ZIKV infection can enhance future severe dengue disease for some DENV serotypes while protecting against other serotypes. Further, prior DENV immunity has not been shown to enhance future uncomplicated or severe Zika and instead appears to be protective. Interestingly, secondary ZIKV infection induces type-specific ZIKV immunity but only generates weakly cross-neutralizing anti-DENV/ZIKV immunity, consistent with risk of future dengue disease. In contrast, secondary DENV infection induces strongly cross-neutralizing antibodies that protect against subsequent severe dengue disease. These immunologic interactions may be explained by differences in virion structure between DENV 1-4 and ZIKV, which modulate thermostability, susceptibility to neutralization, and cell infectivity. Overall, these observations are important for the understanding and prediction of epidemics and the development and evaluation of dengue and Zika vaccines.

Zika Virus Inhibits IFN-α Response by Human Plasmacytoid Dendritic Cells and Induces NS1-Dependent Triggering of CD303 (BDCA-2) Signaling.

Zika virus (ZIKV) dramatically emerged in French Polynesia and subsequently in the Americas where it has been associated with severe neurological complications in adults and newborns, respectively. Although plasmacytoid dendritic cells (pDCs) are a key sensor of viral infection and are critical for initiating an antiviral response, little is known about the impact of ZIKV infection on pDCs. Here, we investigated the susceptibility of human pDCs to infection with multiple strains of ZIKV and further investigated the impact of infection on pDCs functions. We observed that pDCs were refractory to cell-free ZIKV virions but were effectively infected when co-cultured with ZIKV-infected cells. However, exposure of pDCs to ZIKV-infected cells resulted in limited maturation/activation with significant down regulation of CD303 expression, a severe impairment of inflammatory cytokine production, and an inability to mount an IFN-α response. We show that ZIKV developed a strategy to inhibit the IFN-α response in primary human pDCs likely mediated through NS1-dependent CD303 signaling, thus suggesting a new mechanism of immune evasion.

Perfectionism dimensions in pregnancy--a study in Portuguese women.

Pregnancy is essentially a physiological event, but neuroendocrinal and psychosocial changes are also important components of this experience. In this context, perceived stress may be enhanced by the activation of certain personality traits, like perfectionism, which in turn may be associated with more psychological distress (PD). The aim of this study was to investigate if perfectionism could be associated with more negative emotional outcomes (PD) in the transition to motherhood and to look at which of the perfectionism dimensions these consequences are specifically linked. The sample comprises 421 pregnant women (mean = 29.8, SD = 4.48 years) who completed measures of perfectionism and mood symptoms. A two-factor model with self-oriented perfectionism (SOP) and socially prescribed perfectionism (SPP) dimensions and a three-factor model with SOP, SPP-others' high standards and SPP-conditional acceptance (CA) factors were explored. Correlations and linear regressions were calculated between perfectionism factors and mood variables. Results showed that higher levels of SPP factors were associated with increased anxiety, depression, anger, fatigue and confusion, with decreased vigour and with more severe depressive symptoms. Our results, in contrast with those from the study of Campbell and DiPaula (2002, In: Flett G, Hewitt P (eds) Perfectionism. Theory, research, and practice. American Psychological Association, Washington, pp 181-198), did not confirm a preferential association between SPP-CA and PD, revealing that both components of SPP were associated with PD.