Psychosocial modifiers of response to stress

The impact of stress upon an organism is far more complex than the simple design of most stress research implies. We offer an expanded model for studying the relation of stressors to pathological outcomes, which takes into account both the adaptive capacity of the organism before the stressor occurs and the defenses marshalled in response to the stressor. The model also distinguishes among the initial responses of alarm, sustained defensive behaviors, and the relatively irreversible endstates which remain after resistance has ended. Realizing that only a multidiscomplinary approach can begin to capture the wholeness of human experience, this research paradigm anticipates that stressors, adaptive capacities, defenses, alarm reactions, and pathologial end-states will take place at the biological, psychological, interpersonal and sociocultural levels simultaneously and successively. Data on life change stress and psychological health outcomes gathered as part of the Air Traffic Controller Health Change Study are analyzed to illustrate the use of the model in identifying psychosocial and biological modifiers of response to stress.     

The postcranial skeletons of the Triassic mammals Eozostrodon, Megazostrodon and Erythrotherium.

The purposes of this monograph are to describe the postcranial skeletons of the earliest known mammals, and to probe, in so far as possible by osteological study, biological questions concerning the habits and adaptations of these late Triassic forms. In this context, information on the background of this investigation is useful. Studies of Mesozoic mammals, begun some 150 years ago, are based on rare and fragmentary fossils, principally jaws and teeth. These investigations have yielded a bare outline of some 120 million years of mammalian evolution-about two-thirds of mammalian history. No assessment of the important biological changes occurring during this time can ever be complete, but major advances are possible as new discoveries provide material that is more complete or that represents a previously unknown evolutionary stage. So tenuous is the evidence that at least some concepts are re-evaluated with each discovery. Postcranial anatomy offers especially intriguing prospects for investigation because associated material (that can be positively assigned to a taxon below subclass) has been for the most part unknown, and indeed even dissociated bones are a rarity. Since G.G. Simpson's monographs of 1928 and 1929, progress in the study of Mesozoic mammals has been largely dependent on new finds. A major impetus to renewed investigation came from the discoveries of Mesozoic mammals by Walter Kühne in 1939 and during the immediate post-war years. Kühne first worked on fissures in the Carboniferous limestone quarries at Frome, Somerset, in southwest England where he collected a series of teeth of the problematical form Haramiya and two triconodont teeth which were placed in the genus Eozostrodon (Parrington 1941, 1946). The fissure faunas are generally thought to be of Upper Triassic (Rhaetic) age (Kühne 1946), although Kermack, Musset & Rigney (1973) believe that the evidence is insufficient to determine whether the deposits are Rhaetic or Lower Liassic. After the war Kühne carried his explorations farther west, eventually reaching the quarries at Bridgend in Glamorgan, Wales, where he not only found more triconodont teeth in some quantity (Kühne 1958) but also a symmetrodont tooth (Kühne 1950). Shortly after making these discoveries, Kühne returned to Germany and the work was continued by a team from University College, London, under the leadership of Dr K.A. Kermack.     

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.     

Removal of endotoxin by reverse phase HPLC abolishes anti-endothelial cell activity of bacterially expressed plasminogen kringle 5

The success of recombinant protein expression/purification in Escherichia coli depends on a high-fidelity system rendering purified proteins free of confounding contaminants such as endotoxin. Here we report on the expression and purification of a cryptic plasminogen-derived domain, kringle 5, which was previously reported to specifically inhibit endothelial cell growth and, therefore, angiogenesis. Using a histidine (HIS)-tag expression and Ni(+)-NTA agarose purification system identical to previous reports, we found that our purified recombinant kringle 5 did inhibit endothelial cell growth, but this activity could not be eradicated by heat denaturing or proteolysis of kringle 5 with various proteases. This led us to suspect the presence of a contaminant in the purified samples. Quantitative endotoxin testing using a limulus amoebocyte lysate assay revealed that all samples purified by Ni(+)-NTA agarose alone harbored high concentrations of endotoxin that could not be removed by additional purification on anion exchange chromatography. Finally, when kringle 5 was rendered endotoxin-free by purification on reverse phase high-performance liquid chromatography (HPLC), there was a complete loss of endothelial cell growth inhibitory activity. These results strongly suggest that endotoxin-free recombinant kringle 5 may not possess anti-angiogenic activity and demonstrates that, especially in angiogenesis type assays, endotoxin contamination can lead to a misinterpretation of results.