Emerging Viruses: Coming in on a Wrinkled Wing and a Prayer

The role that bats have played in the emergence of several new infectious diseases has been under review. Bats have been identified as the reservoir hosts of newly emergent viruses such as Nipah virus, Hendra virus, and severe acute respiratory syndrome–like coronaviruses. This article expands on recent findings about bats and viruses and their relevance to human infections. It briefly reviews the history of chiropteran viruses and discusses their emergence in the context of geography, phylogeny, and ecology. The public health and trade impacts of several outbreaks are also discussed. Finally, we attempt to predict where, when, and why we may see the emergence of new chiropteran viruses.

Emerging trends at the interface of chemistry and biology: Applications to the design of human therapeutics

This article describes recent developments in the design and implementation of various strategies towards the development of novel therapeutics using first principles from biology and chemistry. Strategies for multi-target therapeutics and network analysis with a focus on cancer and HIV are discussed. Methods for gene and siRNA delivery are presented along with challenges and opportunities for siRNA therapeutics. Advances in protein design methodology and screening are described, with a focus on their application to the design of antibody based therapeutics. Future advances in this area relevant to vaccine design are also mentioned.

The right to humanitarian assistance in natural and human-made disasters: progress and challenges for an emerging international legal framework

Natural and human-made disasters cause on average 120,000 deaths and over US$140 billion in damage to property and infrastructure every year, with national, regional and international actors consistently responding to the humanitarian imperative to alleviate suffering wherever it may be found. Despite various attempts to codify international disaster laws since the 1920s, a right to humanitarian assistance remains contested, reflecting concerns regarding the relative importance of state sovereignty vis-à-vis individual rights under international law. However, the evolving acquis humanitaire of binding and non-binding normative standards for responses to humanitarian crises highlights the increasing focus on rights and responsibilities applicable in disasters; although the International Law Commission has also noted the difficulty of identifying lex lata and lex ferenda regarding the protection of persons in the event of disasters due to the “amorphous state of the law relating to international disaster response.” Therefore, using the conceptual framework of transnational legal process, this thesis analyses the evolving normative frameworks and standards for rights-holders and duty-bearers in disasters. Determining the process whereby rights are created and evolve, and their potential internalisation into domestic law and policy, provides a powerful analytical framework for examining the progress and challenges of developing accountable responses to major disasters.

Regulation of TGF-β1-Driven Differentiation of Human Lung Fibroblasts: Emerging Roles of Cathepsin B and Cystatin C

Lung matrix homeostasis partly depends on the fine regulation of proteolytic activities. We examined the expression of human cysteine cathepsins (Cats) and their relative contribution to TGF-β1-induced fibroblast differentiation into myofibroblasts. Assays were conducted using both primary fibroblasts obtained from patients with idiopathic pulmonary fibrosis (IPF) and human lung CCD-19Lu fibroblasts. Pharmacological inhibition and genetic silencing of Cat B diminished α-smooth muscle actin expression, delayed fibroblast differentiation and led to an accumulation of intracellular 50-kDa TGF-β1. Moreover addition of Cat B generated 25-kDa mature form of TGF-β1 in Cat B siRNA-pretreated lysates. Inhibition of Cat B decreased Smad 2/3 phosphorylation, but had no effect on p38 MAPK and JNK phosphorylation indicating that Cat B mostly disturbs TGF-β1-driven canonical Smad signaling pathway. While mRNA expression of cystatin C was stable, its secretion, which was inhibited by brefeldin A, increased during TGF-β1-induced differentiation of IPF and CCD-19Lu fibroblasts. In addition cystatin C participated in the control of extracellular Cats, since its gene silencing restored their proteolytic activities. These data support the notion that Cat B participates in lung myofibrogenesis as suggested for stellate cells during liver fibrosis. Moreover, we propose that TGF-β1 promotes fibrosis by driving the effective cystatin C-dependent inhibition of extracellular matrix-degrading Cats.

Metalloestrogens: an emerging class of inorganic xenoestrogens with potential to add to the oestrogenic burden of the human breast

Many compounds in the environment have been shown capable of binding to cellular oestrogen receptors and then mimicking the actions of physiological oestrogens. The widespread origin and diversity in chemical structure of these environmental oestrogens is extensive but to date such compounds have been organic and in particular phenolic or carbon ring structures of varying structural complexity. Recent reports of the ability of certain metal ions to also bind to oestrogen receptors and to give rise to oestrogen agonist responses in vitro and in vivo has resulted in the realisation that environmental oestrogens can also be inorganic and such xenoestrogens have been termed metalloestrogens. This report highlights studies which show metalloestrogens to include aluminium, antimony, arsenite, barium, cadmium, chromium (Cr(II)), cobalt, copper, lead, mercury, nickel, selenite, tin and vanadate. The potential for these metal ions to add to the burden of aberrant oestrogen signalling within the human breast is discussed. Copyright (c) 2006 John Wiley & Sons, Ltd.

Stenotrophomonas maltophilia: an emerging opportunist human pathogen

Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen in the debilitated host. S maltophilia is not an inherently virulent pathogen, but its ability to colonise respiratory-tract epithelial cells and surfaces of medical devices makes it a ready coloniser of hospitalised patients. S maltophilia can cause blood-stream infections and pneumonia with considerable morbidity in immunosuppressed patients. Management of infection is hampered by high-level intrinsic resistance to many antibiotic classes and the increasing occurrence of acquired resistance to the first-line drug co-trimoxazole. Prevention of acquisition and infection depends upon the application of modern infection-control practices, with emphasis on the control of antibiotic use and environmental reservoirs.

Extended-spectrum cephalosporin-resistant Gram-negative organisms in livestock: an emerging problem for human health?

Escherichia coli, Salmonella spp. and Acinetobacter spp. are important human pathogens. Serious infections due to these organisms are usually treated with extended-spectrum cephalosporins (ESCs). However, in the past two decades we have faced a rapid increasing of infections and colonization caused by ESC-resistant (ESC-R) isolates due to production of extended-spectrum-β-lactamases (ESBLs), plasmid-mediated AmpCs (pAmpCs) and/or carbapenemase enzymes. This situation limits drastically our therapeutic armamentarium and puts under peril the human health. Animals are considered as potential reservoirs of multidrug-resistant (MDR) Gram-negative organisms. The massive and indiscriminate use of antibiotics in veterinary medicine has contributed to the selection of ESC-R E. coli, ESC-R Salmonella spp. and, to less extent, MDR Acinetobacter spp. among animals, food, and environment. This complex scenario is responsible for the expansion of these MDR organisms which may have life-threatening clinical significance. Nowadays, the prevalence of food-producing animals carrying ESC-R E. coli and ESC-R Salmonella (especially those producing CTX-M-type ESBLs and the CMY-2 pAmpC) has reached worryingly high values. More recently, the appearance of carbapenem-resistant isolates (i.e., VIM-1-producing Enterobacteriaceae and NDM-1 or OXA-23-producing Acinetobacter spp.) in livestock has even drawn greater concerns. In this review, we describe the aspects related to the spread of the above MDR organisms among pigs, cattle, and poultry, focusing on epidemiology, molecular mechanisms of resistance, impact of antibiotic use, and strategies to contain the overall problem. The link and the impact of ESC-R organisms of livestock origin for the human scenario are also discussed.

Targeting membrane-bound viral RNA synthesis reveals potent inhibition of diverse coronaviruses including the middle East respiratory syndrome virus.

Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections.

West African Migrants in Spain: Human Factors and Emerging International Policy. ACES Working Paper No. 6, Fall 2008

This paper concerns itself with the recent phenomenon of West Africans leaving the African continent and seeking work in Spain. By the year 2003, a barely noticeable blip on the screen of the age-old phenomenon that is migration became a conspicuous trend. Depending on one's perspective this trend is either a natural flow of people from one region to another, or it is an alarming turn of events that needs immediate global attention. However, when it involves significant loss of life - as does the sea journey of the poorest aspirants - surely all who ponder the migrant question would agree that this qualifies as a crisis. The next question becomes, then, is it best to focus on minimizing the risks or to focus on deterring the would-be migrants at the onset of their journey? This question and its possible answer are further nuanced by whether those determined to leave receive incentives for choosing to stay at home or whether government officials and others who respond to the crisis in both sending and receiving countries practice a forceful type of deterrent that merely halts the process of migration but does not tackle the issue of why the person chose to leave in the first place.

Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments

After initial infection, human cytomegalovirus remains in a persistent state with the host. Immunity against the virus controls replication, although intermitent viral shedding can still take place in the seropositive immunocompetent person. Replication of cytomegalovirus in the absence of an effective immune response is central to the pathogenesis of disease. Therefore, complications are primarily seen in individuals whose immune system is immature, or is suppressed by drug treatment or coinfection with other pathogens. Although our increasing knowledge of the host-virus relationship has lead to the development of new pharmacological strategies for cytomegalovirus-associated infections, these strategies all have limitations-eg, drug toxicities, development of resistance, poor oral bioavailability, and low potency. Immune-based therapies to complement pharmacological strategies for the successful treatment of virus-associated complications should be prospectively investigated.

Emerging of human factor in risk analysis of home care service

Risk management in healthcare represents a group of various complex actions, implemented to improve the quality of healthcare services and guarantee the patients safety. Risks cannot be eliminated, but it can be controlled with different risk assessment methods derived from industrial applications and among these the Failure Mode Effect and Criticality Analysis (FMECA) is a largely used methodology. The main purpose of this work is the analysis of failure modes of the Home Care (HC) service provided by local healthcare unit of Naples (ASL NA1) to focus attention on human and non human factors according to the organization framework selected by WHO. © Springer International Publishing Switzerland 2014.