SARS-CoV-2 seropositivity and COVID-19 among 5 years-old Amazonian children and their association with poverty and food insecurity

BackgroundThe epidemiology of childhood SARS-CoV-2 infection and COVID-19-related illness remains little studied in high-transmission tropical settings, partly due to the less severe clinical manifestations typically developed by children and the limited availability of diagnostic tests. To address this knowledge gap, we investigate the prevalence and predictors of SARS-CoV-2 infection (either symptomatic or not) and disease in 5 years-old Amazonian children.Methodology/Principal findingsWe retrospectively estimated SARS-CoV-2 attack rates and the proportion of infections leading to COVID-19-related illness among 660 participants in a population-based birth cohort study in the Juruá Valley, Amazonian Brazil. Children were physically examined, tested for SARS-CoV-2 IgG and IgM antibodies, and had a comprehensive health questionnaire administered during a follow-up visit at the age of 5 years carried out in January or June-July 2021. We found serological evidence of past SARS-CoV-2 infection in 297 (45.0%; 95% confidence interval [CI], 41.2–48.9%) of 660 cohort participants, but only 15 (5.1%; 95% CI, 2.9–8.2%) seropositive children had a prior medical diagnosis of COVID-19 reported by their mothers or guardians. The period prevalence of clinically apparent COVID-19, defined as the presence of specific antibodies plus one or more clinical symptoms suggestive of COVID-19 (cough, shortness of breath, and loss of taste or smell) reported by their mothers or guardians since the pandemic onset, was estimated at 7.3% (95% CI, 5.4–9.5%). Importantly, children from the poorest households and those with less educated mothers were significantly more likely to be seropositive, after controlling for potential confounders by mixed-effects multiple Poisson regression analysis. Likewise, the period prevalence of COVID-19 was 1.8-fold (95%, CI 1.2–2.6-fold) higher among cohort participants exposed to food insecurity and 3.0-fold (95% CI, 2.8–3.5-fold) higher among those born to non-White mothers. Finally, children exposed to household and family contacts who had COVID-19 were at an increased risk of being SARS-CoV-2 seropositive and–even more markedly–of having had clinically apparent COVID-19 by the age of 5 years.Conclusions/SignificanceChildhood SARS-CoV-2 infection and COVID-19-associated illness are substantially underdiagnosed and underreported in the Amazon. Children in the most socioeconomically vulnerable households are disproportionately affected by SARS-CoV-2 infection and disease.     

The breakthrough paradox: How focusing on one form of innovation jeopardizes the advancement of science

Research needs a balance of risk‐taking in “breakthrough projects” and gradual progress. For building a sustainable knowledge base, it is indispensable to provide support for both. Subject Categories: Careers, Economics, Law & Politics, Science Policy & Publishing

Science is about venturing into the unknown to find unexpected insights and establish new knowledge. Increasingly, academic institutions and funding agencies such as the European Research Council (ERC) explicitly encourage and support scientists to foster risky and hopefully ground‐breaking research. Such incentives are important and have been greatly appreciated by the scientific community. However, the success of the ERC has had its downsides, as other actors in the funding ecosystem have adopted the ERC’s focus on “breakthrough science” and respective notions of scientific excellence. We argue that these tendencies are concerning since disruptive breakthrough innovation is not the only form of innovation in research. While continuous, gradual innovation is often taken for granted, it could become endangered in a research and funding ecosystem that places ever higher value on breakthrough science. This is problematic since, paradoxically, breakthrough potential in science builds on gradual innovation. If the value of gradual innovation is not better recognized, the potential for breakthrough innovation may well be stifled.

While continuous, gradual innovation is often taken for granted, it could become endangered in a research and funding ecosystem that places ever higher value on breakthrough science.

Concerns that the hypercompetitive dynamics of the current scientific system may impede rather than spur innovative research have been voiced for many years (Alberts et al, 2014). As performance indicators continue to play a central role for promotions and grants, researchers are under pressure to publish extensively, quickly, and preferably in high‐ranking journals (Burrows, 2012). These dynamics increase the risk of mental health issues among scientists (Jaremka et al, 2020), dis‐incentivise relevant and important work (Benedictus et al, 2016), decrease the quality of scientific papers (Sarewitz, 2016) and induce conservative and short‐term thinking rather than risk‐taking and original thinking required for scientific innovation (Alberts et al, 2014; Fochler et al, 2016). Against this background, strong incentives for fostering innovative and daring research are indispensable.     

Myotonia congenita (Thomsen's disease) excluded from the region of the myotonic dystrophy locus on chromosome 19

Summary Linkage analysis has been carried out in six German families with autosomal dominantly inherited myotonia congenita (Thomsen's disease) using five chromosome 19 markers known to be linked to the gene for myotonic dystrophy (DM). Two of the markers, APOC1 and APOC2, are tightly linked to DM. Close linkage between these markers and myotonia congenita (MC) has been excluded to a distance of 9cM (z=-2.158). These data support the clinical suggestion that MC and DM are non-allelic disorders.     

Allele-Specific PCR with Competitive Probe Blocking for Sensitive and Specific Detection of BRAF V600E in Thyroid Fine-Needle Aspiration Specimens

Objective: To detect BRAF V600E mutation in thyroid fine-needle aspiration (FNA) slides and needle rinses (NR). Study Design: Tumor-enriched DNA was extracted from FNA smears, formalin-fixed paraffin-embedded (FFPE) sections, or NR specimens from 37 patients with confirmed papillary thyroid carcinoma or benign findings. An allele-specific primer selectively amplified the 1799 T>A BRAF mutation while simultaneously blocking amplification of wild-type (WT) BRAF with an unlabeled probe during PCR. Mutation detection was accomplished by melting analysis of the probe. Results: Allele-specific/blocking probe PCR confirmed the BRAF mutation status for 20 of 24 paired FNA/FFPE samples previously tested by fluorescent probe real-time PCR. For the other 4 cases, the sensitive PCR method detected the BRAF mutation in all paired FNA/FFPE samples. Previously, the mutation had been detected in only the FFPE samples. The BRAF mutation was also detected in some NR specimens. Conclusion: Treatment of patients with thyroid nodules is guided by FNA biopsy, which can be scantly cellular, necessitating a sensitive test that can detect low levels of BRAF V600E mutation in a WT background. We report increased detection of BRAF V600E in FNA specimens using allele-specific/blocking probe PCR, which has an analytical sensitivity of 0.01%.     

Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease

Dyslipidemia is an important risk factor for cardiovascular disease (CVD) and atherosclerosis. When dyslipidemia coincides with other metabolic disorders such as obesity, hypertension, and glucose intolerance, defined as the metabolic syndrome (MS), individuals present an elevated risk to develop type 2 diabetes (T2D) as well as CVD. Because the MS epidemic represents a growing public health problem worldwide, the development of therapies remains a major challenge. Alterations of bile acid pool regulation in T2D have revealed a link between bile acid and metabolic homeostasis. The bile acid receptors farnesoid X receptor (FXR) and TGR5 both regulate lipid, glucose, and energy metabolism, rendering them potential pharmacological targets for MS therapy. This review discusses the mechanisms of metabolic regulation by FXR and TGR5 and the utility relevance of natural and synthetic modulators of FXR and TGR5 activity, including bile acid sequestrants, in the treatment of the MS.     

Timing and size of blooms of the ctenophore Mnemiopsis leidyi in relation to temperature in Narragansett Bay, RI

The ctenophore Mnemiopsis leidyi is at the northern extreme of its geographic range in Narragansett Bay, an estuary on the northeast coast of the United States. Blooms have typically been observed in late summer and fall according to records from 1950 to 1979. We document an expansion of the seasonal range of this important planktonic predator to include springtime blooms during the 1980s and 1990s. This shift to an earlier seasonal maximum is associated with increasing water temperature in Narragansett Bay. Temperatures in spring have risen, on average, 2 °C from 1950 to 1999 with warm years being associated with the positive phase of the North Atlantic Oscillation. During 1999, M. leidyi appeared earlier in spring and was more abundant than during any previous year for which records are available. Changes in the seasonal pattern and abundance of this predator are likely to have important effects on planktonic ecosystem dynamics of Narragansett Bay. These include reduction of zooplankton abundance in spring followed by increases in size and frequency of summer phytoplankton blooms. Earlier blooms of M. leidyi may also reduce survival of eggs and larvae of fish because, as in 1999, they coincide with the period of peak spawning.     

Subcellular localization, oligomerization, and ATP-binding of Caenorhabditis elegans CED-4.

Caspase family cell death proteases are activated during apoptosis through the oligomerization of caspase-binding "adapter" proteins. In the nematode Caenorhabditis elegans one adapter protein, CED-4, exists. Here we report an analysis of CED-4 protein expressed in insect Sf9 cells by infection with recombinant baculovirus. During expression, CED-4 assumed a perinuclear spherical or reticular localization where it was partly resistant to extraction with nonionic detergents. Both purified FLAG-CED-4 and GST-FLAG-CED-4 proteins were present in solution as large complexes. FLAG-CED-4 complexes were estimated by gel filtration to have a molecular weight of approximately 500 kDa to >1.2 MDa, while GST-FLAG-CED-4 complexes appeared somewhat smaller. Unlike its mammalian homologue Apaf-1, CED-4 exhibited a marked preference for ATP over dATP in filter binding studies and in competition experiments. ATP hydrolysis was required neither for complex stability nor for binding of CED-3. These features are likely to be relevant for CED-4's function as a caspase adapter.     

Fragile X related protein 1 isoforms differentially modulate the affinity of fragile X mental retardation protein for G-quartet RNA structure

Fragile X syndrome, the most frequent form of inherited mental retardation, is due to the absence of expression of the Fragile X Mental Retardation Protein (FMRP), an RNA binding protein with high specificity for G-quartet RNA structure. FMRP is involved in several steps of mRNA metabolism: nucleocytoplasmic trafficking, translational control and transport along dendrites in neurons. Fragile X Related Protein 1 (FXR1P), a homologue and interactor of FMRP, has been postulated to have a function similar to FMRP, leading to the hypothesis that it can compensate for the absence of FMRP in Fragile X patients. Here we analyze the ability of three isoforms of FXR1P, expressed in different tissues, to bind G-quartet RNA structure specifically. Only the longest FXR1P isoform was found to be able to bind specifically the G-quartet RNA, albeit with a lower affinity as compared to FMRP, whereas the other two isoforms negatively regulate the affinity of FMRP for G-quartet RNA. This result is important to decipher the molecular basis of fragile X syndrome, through the understanding of FMRP action in the context of its multimolecular complex in different tissues. In addition, we show that the action of FXR1P is synergistic rather than compensatory for FMRP function.     

Dracula’s ménagerie: A multispecies occupancy analysis of lynx,wildcat, and wolf in the Romanian Carpathians

1. The recovery of terrestrial carnivores in Europe is a conservation success story. Initiatives focused on restoring top predators require information on how resident species may interact with the re‐introduced species as their interactions have the potential to alter food webs, yet such data are scarce for Europe.
2. In this study, we assessed patterns of occupancy and interactions between three carnivore species in the Romanian Carpathians. Romania houses one of the few intact carnivore guilds in Europe, making it an ideal system to assess intraguild interactions and serve as a guide for reintroductions elsewhere.
3. We used camera trap data from two seasons in Transylvanian forests to assess occupancy and co‐occurrence of carnivores using multispecies occupancy models.
4. Mean occupancy in the study area was highest for lynx (Ψ_winter = 0.76 95% CI: 0.42–0.92; Ψ_autumn = 0.71 CI: 0.38–0.84) and wolf (Ψ_winter = 0.60 CI: 0.34–0.78; Ψ_autumn = 0.81 CI: 0.25–0.95) and lowest for wildcat (Ψ_winter = 0.40 CI: 0.19–0.63; Ψ_autumn = 0.52 CI: 0.17–0.78)
5. We found that marginal occupancy predictors for carnivores varied between seasons. We also found differences in predictors of co‐occurrence between seasons for both lynx‐wolf and wildcat‐wolf co‐occurrence. For both seasons, we found that conditional occupancy probabilities of all three species were higher when another species was present.
6. Our results indicate that while there are seasonal differences in predictors of occupancy and co‐occurrence of the three species, co‐occurrence in our study area is high.
7. Terrestrial carnivore recovery efforts are ongoing worldwide. Insights into interspecific relations between carnivore species are critical when considering the depauperate communities they are introduced in. Our work showcases that apex carnivore coexistence is possible, but dependent on protection afforded to forest habitats and their prey base.