Block of death-receptor apoptosis protects mouse cytomegalovirus from macrophages and is a determinant of virulence in immunodeficient hosts.

The inhibition of death-receptor apoptosis is a conserved viral function. The murine cytomegalovirus (MCMV) gene M36 is a sequence and functional homologue of the human cytomegalovirus gene UL36, and it encodes an inhibitor of apoptosis that binds to caspase-8, blocks downstream signaling and thus contributes to viral fitness in macrophages and in vivo. Here we show a direct link between the inability of mutants lacking the M36 gene (ΔM36) to inhibit apoptosis, poor viral growth in macrophage cell cultures and viral in vivo fitness and virulence. ΔM36 grew poorly in RAG1 knockout mice and in RAG/IL-2-receptor common gamma chain double knockout mice (RAGγC(-/-)), but the depletion of macrophages in either mouse strain rescued the growth of ΔM36 to almost wild-type levels. This was consistent with the observation that activated macrophages were sufficient to impair ΔM36 growth in vitro. Namely, spiking fibroblast cell cultures with activated macrophages had a suppressive effect on ΔM36 growth, which could be reverted by z-VAD-fmk, a chemical apoptosis inhibitor. TNFα from activated macrophages synergized with IFNγ in target cells to inhibit ΔM36 growth. Hence, our data show that poor ΔM36 growth in macrophages does not reflect a defect in tropism, but rather a defect in the suppression of antiviral mediators secreted by macrophages. To the best of our knowledge, this shows for the first time an immune evasion mechanism that protects MCMV selectively from the antiviral activity of macrophages, and thus critically contributes to viral pathogenicity in the immunocompromised host devoid of the adaptive immune system

Safety and outcomes of routine endovascular thrombectomy in large artery occlusion recorded in the SITS Register: An observational study

Background and objective We aimed to evaluate the safety and outcomes of thrombectomy in anterior circulation acute ischaemic stroke recorded in the SITS-International Stroke Thrombectomy Register (SITS-ISTR) and compare them with pooled randomized controlled trials (RCTs) and two national registry studies. Methods We identified centres recording >= 10 consecutive patients in the SITS-ISTR with at least 70% of available modified Rankin Scale (mRS) at 3 months during 2014-2019. We defined large artery occlusion as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Outcome measures were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial haemorrhage (SICH) per modified SITS-MOST. Results Results are presented in the following order: SITS-ISTR, RCTs, MR CLEAN Registry and German Stroke Registry (GSR). Median age was 73, 68, 71 and 75 years; baseline NIHSS score was 16, 17, 16 and 15; prior intravenous thrombolysis was 62%, 83%, 78% and 56%; onset to reperfusion time was 289, 285, 267 and 249 min; successful recanalization (mTICI score 2b or 3) was 86%, 71%, 59% and 83%; functional independence at 3 months was 45.5% (95% CI: 44-47), 46.0% (42-50), 38% (35-41) and 37% (35-41), respectively; death was 19.2% (19-21), 15.3% (12.7-18.4), 29.2% (27-32) and 28.6% (27-31); and SICH was 3.6% (3-4), 4.4% (3.0-6.4), 5.8% (4.7-7.1) and not available. Conclusion Thrombectomy in routine clinical use registered in the SITS-ISTR showed safety and outcomes comparable to RCTs, and better functional outcomes and lower mortality than previous national registry studies.Peer reviewe

CrowdHEALTH: Holistic Health Records and Big Data Analytics for Health Policy Making and Personalized Health.

Today's rich digital information environment is characterized by the multitude of data sources providing information that has not yet reached its full potential in eHealth. The aim of the presented approach, namely CrowdHEALTH, is to introduce a new paradigm of Holistic Health Records (HHRs) that include all health determinants. HHRs are transformed into HHRs clusters capturing the clinical, social and human context of population segments and as a result collective knowledge for different factors. The proposed approach also seamlessly integrates big data technologies across the complete data path, providing of Data as a Service (DaaS) to the health ecosystem stakeholders, as well as to policy makers towards a "health in all policies" approach. Cross-domain co-creation of policies is feasible through a rich toolkit, being provided on top of the DaaS, incorporating mechanisms for causal and risk analysis, and for the compilation of predictions

The CrowdHEALTH project and the Hollistic Health Records: Collective Wisdom Driving Public Health Policies.

Introduction: With the expansion of available Information and Communication Technology (ICT) services, a plethora of data sources provide structured and unstructured data used to detect certain health conditions or indicators of disease. Data is spread across various settings, stored and managed in different systems. Due to the lack of technology interoperability and the large amounts of health-related data, data exploitation has not reached its full potential yet. Aim: The aim of the CrowdHEALTH approach, is to introduce a new paradigm of Holistic Health Records (HHRs) that include all health determinants defining health status by using big data management mechanisms. Methods: HHRs are transformed into HHRs clusters capturing the clinical, social and human context with the aim to benefit from the collective knowledge. The presented approach integrates big data technologies, providing Data as a Service (DaaS) to healthcare professionals and policy makers towards a "health in all policies" approach. A toolkit, on top of the DaaS, providing mechanisms for causal and risk analysis, and for the compilation of predictions is developed. Results: CrowdHEALTH platform is based on three main pillars: Data & structures, Health analytics, and Policies. Conclusions: A holistic approach for capturing all health determinants in the proposed HHRs, while creating clusters of them to exploit collective knowledge with the aim of the provision of insight for different population segments according to different factors (e.g. location, occupation, medication status, emerging risks, etc) was presented. The aforementioned approach is under evaluation through different scenarios with heterogeneous data from multiple sources

RNAi in the regulation of mammalian viral infections

Although RNA interference (RNAi) is known to play an important part in defense against viruses of invertebrates, its contribution to mammalian anti-viral defense has been a matter of dispute. This is surprising because all components of the RNAi machinery necessary for robust RNAi-mediated restriction of viruses are conserved in mammals, and the introduction of synthetic small interfering RNAs (siRNAs) into cells efficiently silences the replication of viruses that contain siRNA complementary sequences in those cells. Here, I discuss the reasons for the dispute, and review the evidence that RNAi is a part of the physiological defense of mammalian cells against viral infections

Influence of the quality implementation of a physical education curriculum on the physical development and physical fitness of children

<p>Abstract</p> <p>Background</p> <p>This study was constructed as a comparison group pre-test/post-test quasi-experiment to assess the effect of the implementation of the PE curriculum by specialist PE teachers on children's physical development and physical fitness.</p> <p>Methods</p> <p>146 classes from 66 Slovenian primary schools were assigned to quasi-test (71) and quasi-control (75) groups. Data from the SLOFIT database was used to compare the differences in physical fitness and development between groups of children whose PE lessons were delivered by specialist PE teachers from the second grade onwards (quasi-test, n = 950) or by generalist teachers in all first three grades (quasi-control, n = 994). The Linear Mixed Model was used to test the influence of specialist PE teachers' teaching.</p> <p>Results</p> <p>The quasi-control group showed significantly lower improvement of physical fitness by -0.07 z-score units (95% CI -0.12 to 0.02) compared to the quasi-test group. A significant difference of -0.20 (-0.27 to -0.13) was observed in explosive strength, and of -0.15 (-0.23 to -0.08) in running speed, and in flexibility by -0.22 (-0.29 to -0.14). No significant differences in physical development were observed.</p> <p>Conclusions</p> <p>Specialist PE teachers were more successful than generalist teachers in achieving greater improvement of children's physical fitness, but no differences were observed in physical development of quasi-test and quasi-control group.</p

Genetic identification of cytomegaloviruses in a rural population of Côte d'Ivoire.

BACKGROUND: Cytomegaloviruses (CMVs) are herpesviruses that infect many mammalian species, including humans. Infection generally passes undetected, but the virus can cause serious disease in individuals with impaired immune function. Human CMV (HCMV) is circulating with high seroprevalence (60-100 %) on all continents. However, little information is available on HCMV genoprevalence and genetic diversity in subsaharan Africa, especially in rural areas of West Africa that are at high risk of human-to-human HCMV transmission. In addition, there is a potential for zoonotic spillover of pathogens through bushmeat hunting and handling in these areas as shown for various retroviruses. Although HCMV and nonhuman CMVs are regarded as species-specific, potential human infection with CMVs of non-human primate (NHP) origin, shown to circulate in the local NHP population, has not been studied. FINDINGS: Analysis of 657 human oral swabs and fecal samples collected from 518 individuals living in 8 villages of Côte d'Ivoire with generic PCR for identification of human and NHP CMVs revealed shedding of HCMV in 2.5 % of the individuals. Determination of glycoprotein B sequences showed identity with strains Towne, AD169 and Toledo, respectively. NHP CMV sequences were not detected. CONCLUSIONS: HCMV is actively circulating in a proportion of the rural Côte d'Ivoire human population with circulating strains being closely related to those previously identified in non-African countries. The lack of NHP CMVs in human populations in an environment conducive to cross-species infection supports zoonotic transmission of CMVs to humans being at most a rare event

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income&nbsp;countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was &lt;1.1 kg m–2 in the vast majority of&nbsp;countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

Progress and Research Needs of Plant Biomass Degradation by Basidiomycete Fungi

Peer reviewe