Herpes simplex virus type 1 epidemiology in Latin America and the Caribbean: Systematic review and meta-analytics

Objectives To investigate the epidemiology of herpes simplex virus type 1 (HSV-1) in Latin America and the Caribbean. Methods Systematic review and meta-analytics guided by the Cochrane Collaboration Handbook and reported following the PRISMA guidelines. Results Thirty-three relevant reports were identified including 35 overall (and 95 stratified) seroprevalence measures, and five and nine proportions of virus isolation in genital ulcer disease (GUD) and in genital herpes, respectively. Pooled mean seroprevalence was 57.2% (95% CI: 49.7-64.6%) among children and 88.4% (95% CI: 85.2-91.2%) among adults. Pooled mean seroprevalence was lowest at 49.7% (95% CI: 42.8-56.6%) in those aged ?10, followed by 77.8% (95% CI: 67.9-84.8%) in those aged 10-20, 82.8% (95% CI: 73.1-90.8%) in those aged 20-30, 92.5% (95% CI: 89.4-95.1%) in those aged 30-40, and 94.2% (95% CI: 92.7-95.5%) in those aged ?40. Age was the strongest source of heterogeneity in seroprevalence, explaining 54% of variation. Evidence was found for seroprevalence decline over time. Pooled mean proportion of HSV-1 isolation was 0.9% (95% CI: 0.0-3.6%) in GUD and 10.9% (95% CI: 4.4-19.4%) in genital herpes. Conclusions HSV-1 is a widely prevalent infection in this region, but its epidemiology may be slowly transitioning, with still limited contribution for HSV-1 in genital herpes

The Ethics in Repeat Heart Valve Replacement Surgery

The treatment of patients with intravenous drug use (IVDU) has evolved to include a wide range of medications, psychiatric rehabilitation, and surgical interventions, especially for life-threatening complications such as infective endocarditis (IE). These interventions remain at the discretion of physicians, particularly surgeons, whose treatment decisions are influenced by several medical factors, unfortunately not without bias. The stigma associated with substance use disorder is prevalent, which leads to significant biases, even in the healthcare system. This bias is heightened when IVDU patients require repeat valve replacement surgeries for IE due to continued drug use. Patients who receive a valve replacement and continue to use illicit drugs intravenously often return to their medical providers, months to a few years later, with a reinfection of their bioprosthetic valve; such patients require additional surgeries which are at the center of many ethical discussions due to high mortality rates, for many complex medical and social reasons, associated with continuous chemical dependency after surgical interventions. This chapter examines the ethics of repeat heart valve replacement surgery for patients who are struggling with addiction. Considerations of justice, the fiduciary therapeutic relationship, and guiding ethical principles justify medically beneficial repeat heart valve replacement surgeries for IVDU patient populations

Evaluating the potential of marginal lands available for sustainable cellulosic biofuel production in Italy

The European Union aims to provide as much as one quarter of its transportation fuels via biofuels derived from renewable sources by 2030. To put this into perspective, the Italian government has recently established an ambitious goal to support the wider uptake of advanced second-generation biofuels, including cellulosic biofuels for the transportation sector. A sustainable way forward is to grow perennial biomass crops on marginal lands, however the nationwide availability of those lands for lignocellulosic feedstock production remains uncertain. We identify and evaluate the potential of marginal lands in Italy to produce sizeable amounts of biomass for sustainable cellulosic biofuel production while limiting land use conflicts and negative ecological impacts. We applied spatial multi-criteria decision analysis techniques in geographic information systems to ultimately generate spatially-explicit national land suitability and availability maps at a fine resolution (250-m). We selected a broad range of leading cellulosic biomass crops that includes poplar (Populus × canadensis Moench), willow (Salix alba Linnaeus), black locust (Robinia pseudoacacia Linnaeus), giant reed (Arundo donax Linnaeus), and vetiver grass (Chrysopogon zizanioides Linnaeus). Based on marginality criteria, our results suggest that such biomass plantations of perennial grasses and short rotation trees may produce 3.1–27.4 billion liters of cellulosic ethanol per year from 462,265 to 2,811,064 million hectares of available marginal lands. This estimated production may fulfill 7.8–69.1% of Italy's current liquid transportation fuel consumption, constrained by the requirement that each modelled location be within 70 km of a potential cellulosic biorefinery. Collectively, this study provides the cornerstone of efforts to rationally meet Italy's need for renewable fuels in a sustainable low-carbon economy future

Nanoparticle-mediated targeting of phosphatidylinositol-3-kinase signaling inhibits angiogenesis

Objective: Dysregulation of the phosphatidylinositol-3-kinase (PI3K) signaling pathway is a hallmark of human cancer, occurring in a majority of tumors. Activation of this pathway is critical for transformation and also for the angiogenic switch, which is a key step for tumor progression. The objective of this study was to engineer a PI3K inhibitor-loaded biodegradable nanoparticle and to evaluate its efficacy. Methods and results: Here we report that a nanoparticle-enabled targeting of the PI3K pathway results in inhibition of downstream Akt phosphorylation, leading to inhibition of proliferation and induction of apoptosis of B16/F10 melanoma. It, however, failed to exert a similar activity on MDA-MB-231 breast cancer cells, resulting from reduced internalization and processing of nanoparticles in this cell line. Excitingly, the nanoparticle-enabled targeting of the PI3K pathway resulted in inhibition of endothelial cell proliferation and tubulogenesis, two key steps in tumor angiogenesis. Furthermore, it inhibited both B16/F10- and MDA-MB-231-induced angiogenesis in a zebrafish tumor xenotransplant model. Conclusion: Our study, for the first time, shows that targeting of the PI3K pathway using nanoparticles can offer an attractive strategy for inhibiting tumor angiogenesis

Epidemiology of herpes simplex virus type 2 in sub-Saharan Africa:systematic review, meta-analyses, and meta-regressions

Background: Herpes simplex virus type 2 (HSV-2) infection is a prevalent, sexually transmitted infection with a sizable disease burden that is highest in sub-Saharan Africa. This study aimed to characterize HSV-2 epidemiology in this region. Methods: Cochrane and PRISMA guidelines were followed to systematically review, synthesize, and report HSV-2 related findings up to August 23, 2020. Meta-analyses and meta-regressions were conducted. Findings: From 218 relevant publications, 451 overall outcome measures and 869 stratified measures were extracted. Pooled incidence rates ranged between 2.4–19.4 per 100 person-years across populations. Pooled seroprevalence was lowest at 37.3% (95% confidence interval (CI): 34.9–39.7%) in general populations and high in female sex workers and HIV-positive individuals at 62.5% (95% CI: 54.8–70.0%) and 71.3% (95% CI: 66.5–75.9%), respectively. In general populations, pooled seroprevalence increased steadily with age. Compared to women, men had a lower seroprevalence with an adjusted risk ratio (ARR) of 0.61 (95% CI: 0.56–0.67). Seroprevalence has decreased in recent decades with an ARR of 0.98 (95% CI: 0.97–0.99) per year. Seroprevalence was highest in Eastern and Southern Africa. Pooled HSV-2 proportion in genital ulcer disease was 50.7% (95% CI: 44.7–56.8%) and in genital herpes it was 97.3% (95% CI: 84.4–100%). Interpretation: Seroprevalence is declining by 2% per year, but a third of the population is infected. Age and geography play profound roles in HSV-2 epidemiology. Temporal declines and geographic distribution of HSV-2 seroprevalence mirror that of HIV prevalence, suggesting sexual risk behavior has been declining for three decades. HSV-2 is the etiological cause of half of genital ulcer disease and nearly all genital herpes cases with limited role for HSV-1. Funding: This work was supported by pilot funding from the Biomedical Research Program at Weill Cornell Medicine in Qatar and by the Qatar National Research Fund [NPRP 9–040–3–008]

Phenotypic plasticity, QTL mapping and genomic characterization of bud set in black poplar

<p>Abstract</p> <p>Background</p> <p>The genetic control of important adaptive traits, such as bud set, is still poorly understood in most forest trees species. Poplar is an ideal model tree to study bud set because of its indeterminate shoot growth. Thus, a full-sib family derived from an intraspecific cross of <it>P. nigra </it>with 162 clonally replicated progeny was used to assess the phenotypic plasticity and genetic variation of bud set in two sites of contrasting environmental conditions.</p> <p>Results</p> <p>Six crucial phenological stages of bud set were scored. Night length appeared to be the most important signal triggering the onset of growth cessation. Nevertheless, the effect of other environmental factors, such as temperature, increased during the process. Moreover, a considerable role of genotype × environment (G × E) interaction was found in all phenological stages with the lowest temperature appearing to influence the sensitivity of the most plastic genotypes.</p> <p>Descriptors of growth cessation and bud onset explained the largest part of phenotypic variation of the entire process. Quantitative trait loci (QTL) for these traits were detected. For the four selected traits (the onset of growth cessation (date2.5), the transition from shoot to bud (date1.5), the duration of bud formation (subproc1) and bud maturation (subproc2)) eight and sixteen QTL were mapped on the maternal and paternal map, respectively. The identified QTL, each one characterized by small or modest effect, highlighted the complex nature of traits involved in bud set process. Comparison between map location of QTL and <it>P. trichocarpa </it>genome sequence allowed the identification of 13 gene models, 67 bud set-related expressional and six functional candidate genes (CGs). These CGs are functionally related to relevant biological processes, environmental sensing, signaling, and cell growth and development. Some strong QTL had no obvious CGs, and hold great promise to identify unknown genes that affect bud set.</p> <p>Conclusions</p> <p>This study provides a better understanding of the physiological and genetic dissection of bud set in poplar. The putative QTL identified will be tested for associations in <it>P. nigra </it>natural populations. The identified QTL and CGs will also serve as useful targets for poplar breeding.</p

Glycome and Transcriptome Regulation of Vasculogenesis

Background— Therapeutic vasculogenesis is an emerging concept that can potentially be harnessed for the management of ischemic pathologies. The present study elucidates the potential coregulation of vasculogenesis by the heparan sulfate glycosaminoglycan–rich cell-surface glycome and the transcriptome. Methods and Results— Differentiation of embryonic stem cells into endothelial cells in an in vitro embryoid body is paralleled by an amplification of heparan sulfate glycosaminoglycan sulfation, which correlates with the levels of the enzyme N-deacetylase/N-sulfotransferase 1 (NDST1). Small hairpin RNA–mediated knockdown of NDST1 or modification of heparan sulfate glycosaminoglycans in embryonic stem cells with heparinases or sodium chlorate inhibited differentiation of embryonic stem cells into endothelial cells. This was translated to an in vivo zebrafish embryo model, in which the genetic knockdown of NDST1 resulted in impaired vascularization characterized by a concentration-dependent decrease in intersegmental vessel lumen and a large tail-vessel configuration, which could be rescued by use of exogenous sulfated heparan sulfate glycosaminoglycans. To explore the cross talk between the glycome and the transcriptome during vasculogenesis, we identified by microarray and then validated wild-type and NDST1 knockdown–associated gene-expression patterns in zebrafish embryos. Temporal analysis at 3 developmental stages critical for vasculogenesis revealed a cascade of pathways that may mediate glycocalyx regulation of vasculogenesis. These pathways were intimately connected to cell signaling, cell survival, and cell fate determination. Specifically, we demonstrated that forkhead box O3A/5 proteins and insulin-like growth factor were key downstream signals in this process. Conclusions— The present study for the first time implicates interplay between the glycome and the transcriptome during vasculogenesis, revealing the possibility of harnessing specific cellular glyco-microenvironments for therapeutic vascularization

Expression and Functional Roles of Angiopoietin-2 in Skeletal Muscles

Angiopoietin-1 (ANGPT1) and angiopoietin-2 (ANGPT2) are angiogenesis factors that modulate endothelial cell differentiation, survival and stability. Recent studies have suggested that skeletal muscle precursor cells constitutively express ANGPT1 and adhere to recombinant ANGPT1 and ANGPT2 proteins. It remains unclear whether or not they also express ANGPT2, or if ANGPT2 regulates the myogenesis program of muscle precursors. In this study, ANGPT2 regulatory factors and the effects of ANGPT2 on proliferation, migration, differentiation and survival were identified in cultured primary skeletal myoblasts. The cellular networks involved in the actions of ANGPT2 on skeletal muscle cells were also analyzed.Primary skeletal myoblasts were isolated from human and mouse muscles. Skeletal myoblast survival, proliferation, migration and differentiation were measured in-vitro in response to recombinant ANGPT2 protein and to enhanced ANGPT2 expression delivered with adenoviruses. Real-time PCR and ELISA measurements revealed the presence of constitutive ANGPT2 expression in these cells. This expression increased significantly during myoblast differentiation into myotubes. In human myoblasts, ANGPT2 expression was induced by H(2)O(2), but not by TNFα, IL1β or IL6. ANGPT2 significantly enhanced myoblast differentiation and survival, but had no influence on proliferation or migration. ANGPT2-induced survival was mediated through activation of the ERK1/2 and PI-3 kinase/AKT pathways. Microarray analysis revealed that ANGPT2 upregulates genes involved in the regulation of cell survival, protein synthesis, glucose uptake and free fatty oxidation.Skeletal muscle precursors constitutively express ANGPT2 and this expression is upregulated during differentiation into myotubes. Reactive oxygen species exert a strong stimulatory influence on muscle ANGPT2 expression while pro-inflammatory cytokines do not. ANGPT2 promotes skeletal myoblast survival and differentiation. These results suggest that muscle-derived ANGPT2 production may play a positive role in skeletal muscle fiber repair

Sustainable bioenergy for climate mitigation: Developing drought-tolerant trees and grasses

\u2022 Background and Aims Bioenergy crops are central to climate mitigation strategies that utilize biogenic carbon, such as BECCS (bioenergy with carbon capture and storage), alongside the use of biomass for heat, power, liquid fuels and, in the future, biorefining to chemicals. Several promising lignocellulosic crops are emerging that have no food role \u2013 fast-growing trees and grasses \u2013 but are well suited as bioenergy feedstocks, including Populus, Salix, Arundo, Miscanthus, Panicum and Sorghum. \u2022 Scope These promising crops remain largely undomesticated and, until recently, have had limited germplasm resources. In order to avoid competition with food crops for land and nature conservation, it is likely that future bioenergy crops will be grown on marginal land that is not needed for food production and is of poor quality and subject to drought stress. Thus, here we define an ideotype for drought tolerance that will enable biomass production to be maintained in the face of moderate drought stress. This includes traits that can readily be measured in wide populations of several hundred unique genotypes for genome-wide association studies, alongside traits that are informative but can only easily be assessed in limited numbers or training populations that may be more suitable for genomic selection. Phenotyping, not genotyping, is now the major bottleneck for progress, since in all lignocellulosic crops studied extensive use has been made of next-generation sequencing such that several thousand markers are now available and populations are emerging that will enable rapid progress for drought-tolerance breeding. The emergence of novel technologies for targeted genotyping by sequencing are particularly welcome. Genome editing has already been demonstrated for Populus and offers significant potential for rapid deployment of drought-tolerant crops through manipulation of ABA receptors, as demonstrated in Arabidopsis, with other gene targets yet to be tested. \u2022 Conclusions Bioenergy is predicted to be the fastest-developing renewable energy over the coming decade and significant investment over the past decade has been made in developing genomic resources and in collecting wild germplasm from within the natural ranges of several tree and grass crops. Harnessing these resources for climate-resilient crops for the future remains a challenge but one that is likely to be successful