Genetics of Host Response to Leishmania tropica in Mice – Different Control of Skin Pathology, Chemokine Reaction, and Invasion into Spleen and Liver

Several hundred million people are exposed to the risk of leishmaniasis, a disease caused by intracellular protozoan parasites of several Leishmania species and transmitted by phlebotomine sand flies. In humans, L. tropica causes cutaneous form of leishmaniasis with painful and long-persisting lesions in the site of the insect bite, but the parasites can also penetrate to internal organs. The relationship between the host genes and development of the disease was demonstrated for numerous infectious diseases. However, the search for susceptibility genes in the human population could be a difficult task. In such cases, animal models may help to discover the role of different genes in interactions between the parasite and the host. Unfortunately, the literature contains only a few publications about the use of animals for L. tropica studies. Here, we report an animal model suitable for genetic, pathological and drug studies in L. tropica infection. We show how the host genotype influences different disease symptoms: skin lesions, parasite dissemination to the lymph nodes, spleen and liver, and increase of levels of chemokines CCL2, CCL3 and CCL5 in serum

Genetic Control of Resistance to Trypanosoma brucei brucei Infection in Mice

Trypanosoma brucei are extracellular protozoa transmitted to mammalian host by the tsetse fly. They developed several mechanisms that subvert host's immune defenses. Therefore analysis of genes affecting host's resistance to infection can reveal critical aspects of host-parasite interactions. Trypanosoma brucei brucei infects many animal species including livestock, with particularly severe effects in horses and dogs. Mouse strains differ greatly in susceptibility to T. b. brucei. However, genes controlling susceptibility to this parasite have not been mapped. We analyzed the genetic control of survival after T. b. brucei infection using CcS/Dem recombinant congenic (RC) strains, each of which contains a different random set of 12.5% genes of their donor parental strain STS/A on the BALB/c genetic background. The RC strain CcS-11 is even more susceptible to parasites than BALB/c or STS/A. In F2 hybrids between BALB/c and CcS-11 we detected and mapped four loci, Tbbr1-4 (Trypanosoma brucei brucei response 1–4), that control survival after T. b. brucei infection. Tbbr1 (chromosome 3) and Tbbr2 (chromosome 12) have independent effects, Tbbr3 (chromosome 7) and Tbbr4 (chromosome 19) were detected by their mutual inter-genic interaction. Tbbr2 was precision mapped to a segment of 2.15 Mb that contains 26 genes

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

The United States in the Middle East (2001–2014): from intervention to retrenchment/Os EUA no Oriente Médio (2001–2014): da intervenção ao cerceamento

The main purpose of this paper is to discuss the paradoxical consequences the so-called “Arab Spring”, from 2011 to 2014/15, which has led in various countries of the Arab world and beyond to different outcomes, but nowhere to stable democracy. We intend to discuss the outcomes of those political mobilizations and revolts, paying special attention to (a) the role of Islamist movements and (b) U.S reactions to the recent Mideast upheavals. We start with a general analysis and go to a few case studies (e.g. Egypt, Syria, and Turkey). In discussing the impact of Islamism, we attempt a classification of currents along two coordinates, one parameter contrasting Sunni and Shiite movements, the other laying out the continuum from pacific-modernist to violent jihadist. We defend that the dynamics of intra-Islamist tensions (such as Sunni jihadist against the Shiite Hizbullah-Syria-Iran axis) are no less crucial than the religious-secularist divide for understanding recent developments. Regarding US policies, we emphasize the dilemmas and contradictions within U.S government. We investigate the hypothesis that the US was caught largely unaware by the Arab Spring, and that its reactions suffered from the amorphousness of prior positions of the Obama administration, combined with leftovers from the Bush period. Internal contradictions of Obama’s Middle East doctrine coupled with a general isolationist trend have precluded the US from assuming more forceful policies, creating frustrations on all sides, and enflaming rather than dousing the fires of anti-Westernism in the Islamic world.Keywords: Arab Spring ; U.S policies ; Syria; jihadist.  Resumo: O principal objetivo deste artigo é discutir as consequências paradoxais da chamada "Primavera Árabe", que a partir de 2011 aos nossos dias produziu em vários países do mundo árabe diferentes resultados, mas em nenhum lugar chegou-se à democracia estável. Temos a intenção de discutir os resultados dessas mobilizações políticas e revoltas, com especial atenção para (a) o papel dos movimentos islâmicos e (b) as reações e posturas dos EUA ante os recentes levantes no Oriente Médio. De uma análise geral partiremos para estudos de caso (como Egito, Síria e Turquia). Ao discutir o impacto do islamismo, tentamos uma classificação das correntes ao longo de duas coordenadas, um deles contrastando movimentos sunitas e xiitas, e outro que define o continuum de pacifista - modernista para jihadista –violento. Postulamos que a dinâmica das tensões intra- islâmicos (como a de jihadistas sunitas contra o eixo Hezbollah -Síria- Irã xiita) não são menos importantes do que a divisão religiosa - secular para compreender os desdobramentos recentes. No que diz respeito aos EUA, destacamos os dilemas e contradições dentro do governo dos EUA. Nós investigamos a hipótese de que os EUA foi pego de surpresa em grande parte pela Primavera Árabe, e que as reações do governo Obama traduzem mais um recolhimento do que um novo engajamento.Palavras-chave: Primavera Árabe; Políticas dos EUA; Síria; jihadismo.   DOI: 10.20424/2237-7743/bjir.v4n3p442-47

Temporal trends in stroke admissions in Denmark 1997–2009

BACKGROUND: The Stroke burden is increasing in many populations where health institutions may experience more patients. We wanted to examine whether incidence rates and absolute number of hospitalized stroke patients remained stable in Denmark during a 13 years period where exposure to major stroke risk factors decreased, changes in stroke treatment was implemented, and the age of the population increased. METHODS: The Danish National Patient Register was used to identify all subjects 25 years of age or above admitted with a first time stroke in Denmark from 1997–2009. Incidence rates (IRs) and age-adjusted Poisson regression analyses were used to examine trends in age-, gender- and stroke subtype (ischaemic or unspecified). RESULTS: During the 13-year observation period there were 53.5 million person-years at risk (PY) and a total of 84,626 male and 84,705 female stroke patients were admitted to Danish hospitals. The IRs of hospitalized strokes per 1000 PY was 3.21 (95% confidence interval [CI] 3.16-3.27) in 1997, 3.85 (95% CI 3.79-3.91) in 2003 and 3.22 (95% CI 3.16-3.28) in 2009, respectively. Incidence rate ratios of hospitalized stroke events adjusted for age in the period 2007–2009 compared to 1997–2000 were 0.89 (95% CI 0.87- 0.91) for men and 0.92 (95% CI 0.90-0.94) for women. The incidence of hospitalized unspecified strokes decreased from 1997 to 2009 whereas there was a steep rise in incidence for hospitalization with specified ischemic stroke during this period. CONCLUSION: This study found a constant rate of stroke hospitalization in Denmark from 1997–2009. The overall rate of hospitalized strokes adjusted for age decreased during this period

Comparative gene expression profiling in two congenic mouse strains following <it>Bordetella pertussis </it>infection

<p>Abstract</p> <p>Background</p> <p>Susceptibility to <it>Bordetella pertussis </it>infection varies widely. These differences can partly be explained by genetic host factors. HcB-28 mice are more resistant to <it>B. pertussis </it>infection than C3H mice, which could partially be ascribed to the <it>B</it>. <it>pertussis susceptibility locus-1 </it>(<it>Bps1</it>) on chromosome 12. The presence of C57BL/10 genome on this locus instead of C3H genome resulted in a decreased number of bacteria in the lung. To further elucidate the role of host genetic factors, in particular in the <it>Bps1 </it>locus, in <it>B. pertussis </it>infection, and to identify candidate genes within in this region, we compared expression profiles in the lungs of the C3H and HcB-28 mouse strains following <it>B. pertussis </it>inoculation. Twelve and a half percent of the genomes of these mice are from a different genetic background.</p> <p>Results</p> <p>Upon <it>B. pertussis </it>inoculation 2,353 genes were differentially expressed in the lungs of both mouse strains. Two hundred and six genes were differentially expressed between the two mouse strains, but, remarkably, none of these were up- or down-regulated upon <it>B. pertussis </it>infection. Of these 206 genes, 17 were located in the <it>Bps1 </it>region. Eight of these genes, which showed a strong difference in gene expression between the two mouse strains, map to the immunoglobulin heavy chain complex (<it>Igh</it>).</p> <p>Conclusion</p> <p>Gene expression changes upon <it>B. pertussis </it>infection are highly identical between the two mouse strains despite the differences in the course of <it>B. pertussis </it>infection. Because the genes that were differentially regulated between the mouse strains only showed differences in expression before infection, it appears likely that such intrinsic differences in gene regulation are involved in determining differences in susceptibility to <it>B. pertussis </it>infection. Alternatively, such genetic differences in susceptibility may be explained by genes that are not differentially regulated between these two mouse strains. Genes in the <it>Igh </it>complex, among which <it>Igh-1a/b</it>, are likely candidates to explain differences in susceptibility to <it>B. pertussis</it>. Thus, by microarray analysis we significantly reduced the number of candidate susceptibility genes within the <it>Bps1 </it>locus. Further work should establish the role of the <it>Igh </it>complex in <it>B. pertussis </it>infection.</p