Noncommunicable disease outcomes and the effects of vertical and horizontal health aid

Foreign health aid forms a substantial portion of health spending in many low- and middle-income countries (LMICs). It can be either vertical (funds earmarked for specific diseases) or horizontal (funds used for broad health sector strengthening). Historically, most health aid has been disbursed vertically toward key infectious diseases, with minimal allocations to noncommunicable diseases (NCDs). High NCD burden in LMICs underscores a need for increased assistance toward NCD objectives, but evidence on the outcomes of health aid for NCDs is sparse. We obtained annual data on cause-specific deaths and disability-adjusted life years (DALYs) for four leading NCDs across 116 countries, 2000–2016, and evaluated the relationship between these indicators and vertical and horizontal health aid using country fixed-effects models with 1-to-5-year lagged effects. After adjusting for fixed and time-variant country heterogeneity, vertical assistance for NCDs was significantly associated with subsequent reductions in NCD morbidity and mortality, particularly for persons under age 70 and for cardiovascular and chronic respiratory diseases. An additional dollar in per-capita NCD vertical assistance corresponded to reductions in the average annual NCD burden of 7,459 DALYs/281 deaths after one year, 7,728 DALYs/319 deaths after two years, and 8,957 DALYs/346 deaths after three years. The findings suggest that vertical assistance for NCD programs may be an appropriate mechanism for addressing short-term NCD needs in LMICs, where it may help to fill health sector gaps in NCD care, but longer-term evaluation is needed for assessing the role of horizontal assistance.     

Structural Studies of Streptococcus pyogenes Streptolysin O Provide Insights into the Early Steps of Membrane Penetration

Cholesterol-dependent cytolysins (CDCs) are a large family of bacterial toxins that exhibit a dependence on the presence of membrane cholesterol in forming large pores in cell membranes. Significant changes in the three-dimensional structure of these toxins are necessary to convert the soluble monomeric protein into a membrane pore. We have determined the crystal structure of the archetypical member of the CDC family, streptolysin O (SLO), a virulence factor from Streptococcus pyogenes. The overall fold is similar to previously reported CDC structures, although the C-terminal domain is in a different orientation with respect to the rest of the molecule. Surprisingly, a signature stretch of CDC sequence called the undecapeptide motif, a key region involved in membrane recognition, adopts a very different structure in SLO to that of the well-characterized CDC perfringolysin O (PFO), although the sequences in this region are identical. An analysis reveals that, in PFO, there are complementary interactions between the motif and the rest of domain 4 that are lost in SLO. Molecular dynamics simulations suggest that the loss of a salt bridge in SLO and a cation–pi interaction are determining factors in the extended conformation of the motif, which in turn appears to result in a greater flexibility of the neighboring L1 loop that houses a cholesterol-sensing motif. These differences may explain the differing abilities of SLO and PFO to efficiently penetrate target cell membranes in the first step of toxin insertion into the membrane.     

极化与固化:转基因“科普”的困境分析与路径选择

从中国转基因科普的实践入手,结合国内外经验研究,从传播学、心理学和社会学的维度,辨析了当前转基因科普面临的困境,梳理了公众转基因态度极化和固化的原因。科学知识与转基因接受度的相关度弱,信任、价值和科学体制等诸多因素影响着大众对转基因的态度。据此,提出了中国转基因科学传播的五点可能路径。     

Sexual dimorphism in oxytocin responses to health perception and disgust,with implications for theories on pathogen detection

In response to a recent hypothesis that the neuropeptide oxytocin might be involved in human pathogen avoidance mechanisms, we report the results of a study in which we investigate the effect of intranasal oxytocin on two behaviors serving as proxies for pathogen detection. Participants received either oxytocin or a placebo and were asked to evaluate (1) the health of Caucasian male computer-generated pictures that varied in facial redness (an indicator of hemoglobin perfusion) and (2) a series of pictures depicting disgusting scenarios. Men, but not women, evaluated all faces, regardless of color, as less healthy when given oxytocin compared to a placebo. Women, on the other hand, expressed decreased disgust when given oxytocin compared to a placebo. These results suggest that intranasal oxytocin administration does not facilitate pathogen detection based on visual cues, but instead reveal clear sex differences in the perception of health and sickness cues.     

Inhibition of macrophage DNA synthesis by immunomodulators. II. Characterization of the suppression by muramyl dipeptide or lipopolysaccharide [3H]thymidine incorporation into macrophages

Guinea pig peritoneal exudate macrophages actively incorporated [3H]thymidine into trichloroacetic acid-insoluble fraction in vitro. The incorporation of [3H]thymidine was almost completely inhibited by aphidicolin, an inhibitor of DNA polymerase alpha and an autoradiograph showed heavy labeling in nuclei of 15% of macrophage populations. These results indicate that the observed thymidine incorporation was due to a nuclear DNA synthesis. The [3H]thymidine incorporation was markedly suppressed when macrophages were activated by immunoadjuvants such as muramyl dipeptide (MDP) or bacterial lipopolysaccharide (LPS). The suppression of [3H]thymidine incorporation by MDP was neither due to the decrease in thymidine transport through the cell membrane, nor due to dilution by newly synthesized "cold" thymidine. An autoradiograph revealed that MDP markedly decreased the number of macrophages the nuclei of which were labeled by [3H]thymidine. These results suggest that the suppression of [3H]thymidine incorporation by the immunoadjuvants reflects a true inhibition of DNA synthesis. The inhibition of DNA synthesis by MDP was also observed in vivo. Further, it was strongly suggested that the inhibition was not caused by some mediators, such as prostaglandin E2, released from macrophages stimulated by the immunoadjuvants but caused by a direct triggering of the adjuvants at least at the early stage of activation. Cyclic AMP appears to be involved in the inhibitory reaction.     

Did Covid-19 hit harder in peripheral areas? The case of Italian municipalities

The first wave of Covid-19 pandemic had a geographically heterogeneous impact even within the most severely hit regions. Exploiting a triple-differences methodology, we find that in Italy Covid-19 hit relatively harder in peripheral areas: the excess mortality in peripheral areas was almost double that of central ones in March 2020 (1.2 additional deaths every 1000 inhabitants). We leverage a rich dataset on Italian municipalities to explore mechanisms behind this gradient. We first show that socio-demographic and economic features at municipal level are highly collinear, making it hard to identify single-variable causal relationships. Using Principal Components Analysis we model excess mortality and show that areas with higher excess mortality have lower income, lower education, larger households, lower trade and higher industrial employments, and older population. Our findings highlight a strong centre-periphery gradient in the harshness of Covid-19, which we believe is also highly relevant from a policy-making standpoint.     

The impact of widowhood on wellbeing,health, and care use: A longitudinal analysis across Europe

ObjectiveTo estimate whether becoming widowed had a significant effect on individual’s health status as well as on healthcare and non-healthcare resources use, compared to people who remained in a couple in Europe.Data and methodIt was used the Survey of Health, Aging and Retirement in Europe from 2004 to 2015. The statistical technique used was genetic matching which analysed the differences in wellbeing, mental health, health status, risk of death, health care resources and long-term care utilization of people who have become widowed, comparing with people who remained married or with a partner. We considered shortterm and medium-term effects.ResultsIn the short term, those who became widowed had a worse wellbeing and mental health, in addition to a greater probability of receiving formal care and informal care from outside the household. There seems to be a significant effect in the use of formal and informal care from outside the household in the medium term.ConclusionsThe results might help to concentrate a major effort of any policy or strategy, not only in the field of health but also in the provision of long-term care, immediately after the negative shock occurs.